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- Herausgeber: John Wiley & Sons
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
A Guide to Virology for Engineers and Applied Scientists A hands-on guide covering the fundamentals of virology written from an engineering perspective In A Guide to Virology for Engineers and Applied Scientists: Epidemiology, Emergency Management, and Optimization, a team of distinguished researchers delivers a robust and accessible treatment of virology from an engineering perspective. The book synthesizes a great deal of general information on viruses--including coronaviruses--in a single volume. It provides critical context that engineers and applied scientists can use to evaluate and manage viruses encountered in the environment. The fundamental principles of virology are explored with calculation details for health and hazard risk assessments. Each chapter combines numerous illustrative examples and sample problems ideal for advanced courses in environmental health and safety, pharmaceuticals, and environmental science and engineering. Readers will also find: * A detailed introduction to health and hazard risk analysis and assessment that is complete with technical information and calculation details * Comprehensive illustrative examples and practice problems for use by educators and professionals in training * Practical discussions of virology by authors with combined experience in pharmaceuticals and environmental health and safety * Thorough treatments of virology from the perspective of a professional engineer * A definitive source for those working in related fields who wish to deepen their overall understanding of viruses Perfect for chemical, civil, mechanical, biochemical engineers, and applied scientists, A Guide to Virology for Engineers and Applied Scientists: Epidemiology, Emergency Management, and Optimization will also earn a place in the libraries of industrial hygiene professionals and instructors, students, and practitioners in environmental health, pharmaceuticals, public health, and epidemiology.
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Table of Contents
Cover
Title Page
Copyright
Dedication
Preface
About the Authors
Part I: Introduction to Viruses
1 Overview of Molecular Biology
1.1 CELL BASICS
1.2 CELL REPLICATION
1.3 CELLULAR TRANSPORT
1.4 IMMUNE DEFENSE
1.5 APPLICATIONS
1.6 CHAPTER SUMMARY
1.7 PROBLEMS
REFERENCES
2 Basics of Virology
2.1 VIRAL BASICS AND TERMINOLOGY
2.2 VIRAL LIFE CYCLE
2.3 VIRUS STRUCTURE AND CLASSIFICATION
2.4 VIRUSES IN CONTEXT OF THE TREE OF LIFE
2.5 VIRAL GENETICS
2.6 APPLICATIONS
2.7 CHAPTER SUMMARY
2.8 PROBLEMS
REFERENCES
3 Pandemics, Epidemics, and Outbreaks
3.1 HUMAN VIRAL DISEASES
3.2 EBOLA AND MARBURG VIRUSES
3.3 HUMAN IMMUNODEFICIENCY DISEASE (HIV)
3.4 INFLUENZA
3.5 CORONAVIRUSES
3.6 CURRENT AND EMERGING VIRAL THREATS
3.7 APPLICATIONS
3.8 CHAPTER SUMMARY
3.9 PROBLEMS
REFERENCES
4 Virus Prevention, Diagnosis, and Treatment
4.1 VACCINATION SUCCESSES AND CHALLENGES
4.2 CURRENT VACCINE TECHNOLOGY
4.3 U.S.‐APPROVED VACCINES AND REQUIREMENTS
4.4 VIRAL TESTING AND DIAGNOSIS
4.5 ANTIVIRAL TREATMENT OPTIONS
4.6 APPLICATIONS
4.7 CHAPTER SUMMARY
4.8 PROBLEMS
REFERENCES
5 Safety Protocols and Personal Protection Equipment
5.1 REGULATIONS AND OVERSIGHT OF SAFETY PROTOCOLS
5.2 PROTECTIVE AND SAFETY SYSTEMS
5.3 DISINFECTION CATEGORIES AND PROCEDURES
5.4 OCCUPATIONAL HEALTH AND SAFETY ADMINISTRATION HAZMAT REGULATIONS
5.5 BIO LEVEL SAFETY AND SECURITY
5.6 COVID‐RELATED SAFETY PRECAUTIONS
5.7 APPLICATIONS
5.8 SUMMARY
5.9 PROBLEMS
REFERENCES
6 Epidemiology and Virus Transmission
6.1 OVERVIEW OF EPIDEMIOLOGY
6.2 GOVERNMENT AGENCIES' CONTRIBUTIONS TO PUBLIC HEALTH
6.3 EPIDEMIOLOGIC STUDY DESIGN
6.4 VIRUS TRANSMISSION
6.5 APPLICATIONS
6.6 CHAPTER SUMMARY
6.7 PROBLEMS
REFERENCES
Part II: Practical and Technical Considerations
7 Engineering Principles and Fundamentals
7.1 HISTORY OF ENGINEERING
7.2 PROBLEM SOLVING: THE ENGINEERING APPROACH
7.3 UNITS AND CONVERSION CONSTANTS
7.4 DIMENSIONAL ANALYSIS
7.5 PROCESS VARIABLES
7.6 THE CONSERVATION LAWS
7.7 THERMODYNAMICS AND KINETICS
7.8 APPLICATIONS
7.9 CHAPTER SUMMARY
7.10 PROBLEMS
REFERENCES
8 Legal and Regulatory Considerations
8.1 THE REGULATORY SYSTEM
8.2 THE ROLE OF INDIVIDUAL STATES
8.3 KEY GOVERNMENT AGENCIES
8.4 PUBLIC HEALTH EMERGENCY DECLARATIONS
8.5 KEY ENVIRONMENTAL ACTS
8.6 THE CLEAN AIR ACT
8.7 REGULATION OF TOXIC SUBSTANCES
8.8 REGULATIONS GOVERNING INFECTIOUS DISEASES
8.9 APPLICATIONS
8.10 CHAPTER SUMMARY
8.11 PROBLEMS
REFERENCES
9 Emergency Planning and Response
9.1 THE IMPORTANCE OF EMERGENCY PLANNING AND RESPONSE
9.2 PLANNING FOR EMERGENCIES
9.3 PLAN IMPLEMENTATION
9.4 EP&R FOR EPIDEMICS AND PANDEMICS
9.5 EP&R FOR INDUSTRIAL ACCIDENTS
9.6 EP&R FOR NATURAL DISASTERS
9.7 CURRENT AND FUTURE TRENDS
9.8 APPLICATIONS
9.9 CHAPTER SUMMARY
9.10 PROBLEMS
REFERENCES
10 Ethical Considerations within Virology
10.1 CORE ETHICS PRINCIPLES
10.2 IMPORTANT TENETS OF ETHICAL RESEARCH
10.3 ETHICAL DILEMMAS IN PUBLIC HEALTH
10.4 ETHICAL CONSIDERATIONS REGARDING MEDICAL INTERVENTIONS
10.5 APPLICATIONS
10.6 CHAPTER SUMMARY
10.7 PROBLEMS
REFERENCES
11 Health and Hazard Risk Assessment
11.1 INTRODUCTION TO RISK ASSESSMENT
11.2 THE HEALTH RISK ASSESSMENT PROCESS
11.3 DOSE–RESPONSE ASSESSMENT
11.4 THE HAZARD RISK ASSESSMENT PROCESS
11.5 HAZARD RISK VERSUS HEALTH RISK
11.6 COVID‐19 PANDEMIC HAZARD RISK
11.7 THE UNCERTAINTY FACTOR
11.8 APPLICATIONS
11.9 CHAPTER SUMMARY
11.10 PROBLEMS
REFERENCES
Part III: Engineering Considerations
12 Introduction to Mathematical Methods
12.1 DIFFERENTIATION
12.2 INTEGRATION
12.3 SIMULTANEOUS LINEAR ALGEBRAIC EQUATIONS
12.4 NONLINEAR ALGEBRAIC EQUATIONS
12.5 ORDINARY DIFFERENTIAL EQUATIONS
12.6 PARTIAL DIFFERENTIAL EQUATIONS
12.7 APPLICATIONS
12.8 CHAPTER SUMMARY
12.9 PROBLEMS
REFERENCES
13 Probability and Statistical Principles
13.1 PROBABILITY DEFINITIONS AND INTERPRETATIONS
13.2 INTRODUCTION TO PROBABILITY DISTRIBUTIONS
13.3 DISCRETE PROBABILITY DISTRIBUTIONS
13.4 CONTINUOUS PROBABILITY DISTRIBUTIONS
13.5 CONTEMPORARY STATISTICS
13.6 APPLICATIONS
13.7 CHAPTER SUMMARY
13.8 PROBLEMS
REFERENCES
14 Linear Regression
14.1 RECTANGULAR COORDINATES
14.2 LOGARITHMIC COORDINATES
14.3 METHODS OF PLOTTING DATA
14.4 SCATTER DIAGRAMS
14.5 CURVE FITTING
14.6 METHOD OF LEAST SQUARES
14.7 APPLICATIONS
14.8 CHAPTER SUMMARY
14.9 PROBLEMS
REFERENCES
15 Ventilation
15.1 INTRODUCTION TO INDUSTRIAL VENTILATION SYSTEMS
15.2 COMPONENTS OF VENTILATION SYSTEMS
15.3 FANS, VALVES AND FITTINGS, AND DUCTWORK
15.4 SELECTING VENTILATION SYSTEMS
15.5 KEY PROCESS EQUATIONS
15.6 VENTILATION MODELS
15.7 MODEL LIMITATIONS
15.8 INFECTION CONTROL IMPLICATIONS
15.9 APPLICATIONS
15.10 CHAPTER SUMMARY
15.11 PROBLEMS
REFERENCES
16 Pandemic Health Data Modeling
16.1 COVID‐19: A RUDE AWAKENING
16.2 EARLIER WORK
16.3 PLANNING FOR PANDEMICS
16.4 GENERATING MATHEMATICAL MODELS
16.5 PANDEMIC HEALTH DATA MODELS
16.6 IN REVIEW
16.7 APPLICATIONS
16.8 CHAPTER SUMMARY
16.9 PROBLEMS
REFERENCES
17 Optimization Procedures
17.1 THE HISTORY OF OPTIMIZATION
17.2 THE SCOPE OF OPTIMIZATION
17.3 CONVENTIONAL OPTIMIZATION PROCEDURES
17.4 ANALYTICAL FOMULATION OF THE OPTIMUM
17.5 CONTEMPORARY OPTIMIZATION: CONCEPTS IN LINEAR PROGRAMMING
17.6 APPLIED CONCEPTS IN LINEAR PROGRAMMING
17.7 APPLICATIONS
17.8 CHAPTER SUMMARY
17.9 PROBLEMS
REFERENCES
Index
End User License Agreement
List of Tables
Chapter 3
Table 3.1 Influenza A and B Diagnostic Testing Techniques and Timing of Res...
Chapter 4
Table 4.1 Centers for disease control recommended vaccines for children.
Chapter 8
Table 8.1 Major toxic chemical laws administered by the EPA.
Table 8.2 Microbial contaminants – CCL 4.
Table 8.3 Microorganism surface water treatment rules summary.
Chapter 11
Table 11.1 OSHA risk levels.
Table 11.2 Illustrative Example 11.4 risk calculation.
Chapter 12
Table 12.1 Concentration–time data.
Chapter 13
Table 13.1 The standard normal distribution.
Chapter 14
Table 14.1 Method for plotting various equation functions.
Chapter 16
Table 16.1 Mathematical Models: (Theodore, J, and Theodore, L. 2021)
Table 16.2 New Infection Cases (per 10
3
) vs. Week Number
Table 16.3 New Infections (NI/100) vs Time in weeks (T)
Table 16.4 Early New Infections (NI/100 People) Predictors versus Time Sinc...
List of Illustrations
Chapter 1
Figure 1.1 Illustration of organelles within a cell.
Figure 1.2 DNA polynucleotide base pairs with sugar‐phosphate backbone https...
Figure 1.3 DNA Replication https://www.genome.gov/genetics-glossary/DNA-Repl...
Figure 1.4 Protein Synthesis: Transcription and Translation https://nci-medi...
Chapter 2
Figure 2.1 Cell Connection and Entry. (Source: https://www.genome.gov/about-...
Figure 2.2 Virus Replication and Release. (Source: Adapted from: https://www...
Figure 2.3 Examples of Virus Structures. (Source: https://www.genome.gov/gen...
Figure 2.4 Replication of a Retrovirus. (Source: https://www.genome.gov/gene...
Chapter 3
Figure 3.1 CDC SARS‐CoV‐2 antigen test algorithm for community settings.
Figure 3.2 The National Institute of Allergy and Infectious Diseases Strateg...
Chapter 6
Figure 6.1 Epidemiologic study types. Adapted from
Descriptive and analytic
...
Figure 6.2 Case data stratified by age for a fictional childhood illness dur...
Chapter 7
Figure 7.1 Conservation law example.
Figure 7.2 Bypass, recycle, purge, and makeup.
Chapter 8
Figure 8.1 Size‐efficiency curve.
Chapter 11
Figure 11.1 Health risk assessment flowchart..
Figure 11.2 Hazard risk assessment flowchart.
Chapter 12
Figure 12.1 Trapezoidal rule analysis and error. Source: Courtesy of Abhishe...
Figure 12.2 Simpson's rule analysis and error..
Figure 12.3 Newton–Raphson method for nonlinear equations Source: Courtesy o...
Figure 12.4 Error analysis in numerical calculations..
Chapter 13
Figure 13.1 Areas under a standard normal curve.
Figure 13.2 Various normal curves with different standard deviations..
Figure 13.3 Differently skewed curves..
Figure 13.4 Bathtub curve..
Chapter 14
Figure 14.1 Scatter diagrams: (a) linear relationship, (b) parabolic relatio...
Figure 14.2 Parabola representation.
Figure 14.3 Error difference: actual and modeled predicted values..
Figure 14.4 Death rates: experimental data.
Figure 14.5 Death rates: predicted data.
Figure 14.6 Modified death rate data.
Figure 14.7 Predicted data.
Chapter 15
Figure 15.1 Components of an industrial ventilation system.
Figure 15.2 System and fan characteristics.
Chapter 16
Figure 16.1 Scatter diagrams: (a) linear relationship, (b) parabolic relatio...
Figure 16.2 Pandemic health data plot.
Figure 16.3 Pandemic health data plot comparison.
Figure 16.4 Infection data for
NAHUW4
virus.
Figure 16.5 Plot of Health Data Model.
Figure 16.6 Maximum and minimum of a function with derived curve. Courtesy o...
Figure 16.7 NAHUW4 infection rate data extrapolation based on data availabil...
Chapter 17
Figure 17.1 Two variable minimization problem. (a) Equation (17.28). (b) Equ...
Figure 17.2 Solution to two‐variable minimization problem. (a) Equation 17.2...
Figure 17.3 Possible solution to two variable maximization problem.
Figure 17.4 Graphical solution for maximization problem.
Guide
Cover
Table of Contents
Title Page
Copyright
Dedication
Preface
About the Authors
Begin Reading
Index
End User License Agreement
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A Guide to Virology for Engineers and Applied Scientists
Epidemiology, Emergency Management, and Optimization
Megan M. Reynolds and Louis Theodore
This edition first published 2023© 2023 John Wiley & Sons, Inc.
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.
The right of Megan M. Reynolds and Louis Theodore to be identified as the authors of this work has been asserted in accordance with law.
Registered OfficeJohn Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA
Editorial Office111 River Street, Hoboken, NJ 07030, USA
For details of our global editorial offices, customer services, and more information about Wiley products visit us at www.wiley.com.
Wiley also publishes its books in a variety of electronic formats and by print‐on‐demand. Some content that appears in standard print versions of this book may not be available in other formats.
Trademarks: Wiley and the Wiley logo are trademarks or registered trademarks of John Wiley & Sons, Inc. and/or its affiliates in the United States and other countries and may not be used without written permission. All other trademarks are the property of their respective owners. John Wiley & Sons, Inc. is not associated with any product or vendor mentioned in this book.
Limit of Liability/Disclaimer of WarrantyIn view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of experimental reagents, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each chemical, piece of equipment, reagent, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. While the publisher and authors have used their best efforts in preparing this work, they make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives, written sales materials or promotional statements for this work. The fact that an organization, website, or product is referred to in this work as a citation and/or potential source of further information does not mean that the publisher and authors endorse the information or services the organization, website, or product may provide or recommendations it may make. This work is sold with the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be suitable for your situation. You should consult with a specialist where appropriate. Further, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.
Library of Congress Cataloging‐in‐Publication Data applied for:Hardback ISBN: 9781119853138
Cover Design: WileyCover Image: © Yuichiro Chino/Getty Images
TOMy father, Dr. Joseph P. Reynolds (MMR)
AND
My friends and colleagues working in the field of virology (LT)
“When an epidemic of physical disease starts to spread, the community approves and joins in a quarantine of the patients in order to protect the health of the community against the spread of the disease…”
Franklin Delano Roosevelt (1882–1945)
Preface
As its title implies, this book offers a guide to virology which provides information on viruses from an engineer's and applied scientist's perspective. Concise and easy to use, this guide brings together a wealth of general information on viruses in one compact book. It additionally offers practical and technical information plus calculation details.
The guide has been written not only for students but also for those in technical roles, such as engineers and applied scientists who work in public health, pharmaceuticals, or other health‐related fields. It is a tool that may be used whenever and wherever information about viruses is likely to be sought.
In the wake of the COVID‐19 pandemic, it has become evident that knowledge of virology is no longer critical only to doctors or epidemiologists; there is an urgent need for cooperation among varied disciplines to address the current pandemic and prepare for the next one. The authors feel that no one source currently covers all of the information on viruses in the manner presented in this book. It is hoped that this book will serve to fill the growing need for concise and digestible information – both academically and professionally – in these fields.
The guide is divided into three parts. Part I provides an overview of the science of viruses, including what they are, how they work, and how illnesses can be prevented and treated. Parts II and III provide information on practical/technical considerations and on calculation details, respectively. In addition, a number of illustrative examples are included for each chapter.
Reasonable care has been taken to ensure the accuracy of the information contained in this book. However, the authors and the publisher cannot be held responsible for erroneous omissions in the information presented or for any consequences arising from the use of the information published in the book. Accordingly, reference to original sources is encouraged. Reporting of any errors or omissions is solicited in order to ensure that appropriate changes may be made in future editions.
The authors wish to thank the following individuals for their important contributions to the work: Marybeth R. Radics, Mary K. Theodore, Ann Marie Flynn, and Matthew C. Ogwu.
Finally, the authors also wish to acknowledge the contributing authors: Sarah Forster (Overview of Molecular Biology), Emma Parente (Safety Protocols and Personal Protection Equipment), Vishal Bhatty (Engineering Principles and Fundamentals), Paul DiGaetano, Jr. (Ethical Considerations in Virology), and Julian Theodore (Introduction to Mathematical Methods).
August 2022
Megan M. Reynolds
Merano, Italy
Louis Theodore
East Williston, NY
About the Authors
Megan M. Reynolds, BS, MS, MBA, is a freelance medical writer and editor with a particular focus on infectious diseases. With degrees in chemical engineering, international business, and medicine, she worked in the pharmaceutical field in various capacities for more than a dozen years in both the United States and Europe. Her experience encompasses manufacturing, sales, and marketing from managing production scale‐up for the launch of new drug manufacturing lines to spearheading an education initiative for healthcare providers at a large New York public hospital aimed at increasing vaccine utilization. She also studied methods for minimizing bacterial resistance due to the overuse of antibiotics. Previous publications include textbook chapter contributions, a case report on the successful treatment of a patient with a rare, highly resistant infection, as well as a medical narrative on treating patients in severe pain. Her recent research interests have focused on addressing the high rate of hospital‐acquired infections leading to sepsis and on reducing vaccine hesitancy towards measles, mumps, and rubella vaccine (MMR). Raised in New York City, Ms. Reynolds is multilingual and has lived and worked in several countries, including Italy, Spain, and Germany, and has studied in the United States, Mexico, and Grenada. She is currently based in northern Italy and enjoys living in the Alps while pursuing her passions in rock climbing, yoga, and skiing.
Born and raised in Hell's Kitchen, Louis Theodore received the degrees of MChE and EngScD from the New York University and a BChE from the Cooper Union. For over 50 years, Dr. Theodore was a chemical engineering professor, as well as graduate program director, researcher, professional innovator, and communicator in the engineering field. He has authored numerous texts and reference books, nearly 200 technical papers, and is section editor to the last four editions of Perry's Chemical Engineers' Handbook. He has served as a consultant to the US EPA, DOE and DOJ, and Theodore Tutorials. Dr. Theodore is a member of Phi Lambda Upsilon, Sigma Xi, Tau Beta Pi, American Chemical Society, American Society of Engineering Education, Royal Hellenic Society, and a fellow of the International Air & Waste Management Association (AWMA). In addition to providing invited testimony to a Presidential (Ford) Crime Commission Hearing, Dr. Theodore was honored at Madison Square Garden in 2008 for his contributions to basketball and the youth of America. His current technical interests include risk management, desalination, and pandemic modeling.
Part IIntroduction to Viruses
Merriam‐Webster defines Introduction as “something that introduces, such as,
a part of a book or treatise preliminary to the main portion,
a preliminary treatise or course of study” (Merriam‐Webster 2022)
Indeed, that is exactly what this Part I of the book is all about. The chapters contain material that one might view as a prerequisite for the technical considerations and engineering calculations that are addressed in Parts II and III, respectively.
It is no secret that viruses are responsible for a host of diseases that can include something as simple as the so‐called “common” cold to those that are more serious and fatal, i.e., COVID‐19, West Nile, AIDS, Ebola, etc. The technical community began to realize that viruses, in general, were responsible for a range of diseases at the turn of the 20th century. The variation in disease severity occurs because various viruses attack different tissues and organs. In addition, one of the problems with virus detection has been the extremely small size of many of viruses, i.e., both the SARS‐CoV‐2 and polio viruses are in the 0.01‐0.1‐micron size range.
There are six chapters covering these issues in Part I. The chapter numbers and accompanying titles are listed below:
Chapter 1
: Overview of Molecular Biology
Chapter 2
: Basics of Virology
Chapter 3
: Pandemics, Epidemics, and Outbreaks
Chapter 4
: Virus Prevention, Diagnosis, and Treatment
Chapter 5
: Safety Protocols and Personal Protection Equipment
Chapter 6
: Epidemiology and Virus Transmission
1Overview of Molecular Biology
Contributing Author: Sarah Forster
CHAPTER MENU
Cell Basics
Cell Replication
Cellular Transport
Immune Defense
Applications
Chapter Summary
Problems
References
After much deliberation, the authors have decided to include a preliminary chapter concerned with molecular biology and the immune system. This decision was based on the fact that the book was written for engineers and applied scientists who may not have a background in biology. Why the inclusion? The authors felt that these topics, for those interested, could provide the readers with a better understanding of how cells function under normal circumstances, and thus better comprehend how viruses take over and use these mechanisms against the body.
Biology, as the science of life, involves the general study of living forms. Molecular biology, which includes biophysics and biochemistry, has made fundamental contributions to modern biology. Thus, more information is now available about the structure and function of nucleic acids – the base of DNA and proteins, and the key molecules of all living matter. Cellular biology is closely related to molecular biology (the title of this chapter). It primarily deals with the functions of the cell – the basic structural unit of life – which studies its components and their interactions. The life functions of multicellular organisms are governed by the activities and interactions of their cellular components. The study of organisms includes not only their growth and development but also how they function.
When a virus infects a host, it utilizes the genetic code of the invaded cell to hijack the normal replication process in order to replicate numerous copies of itself. Thus, it is helpful to have some understanding as to how genetic coding works under normal circumstances, in order to fully comprehend the complex mechanism with which the virus commandeers a cell for its own purposes. While viruses are not themselves cellular, they do contain the same basic genetic materials as cells, either DNA or RNA.
This chapter attempts to provide the reader with some of the key terms that have become integral to the study of molecular biology. The chapter also endeavors to offer a framework of normal cell functions critical to the understanding of virology. Chapter 2: Basics of Virology, the next chapter, utilizes this framework to depict how viruses invade and hijack standard cell function. Hopefully, the importance of the definitions and explanations in this earlier section will become clear. In the same vein, those already familiar with molecular biology may wish to skip this chapter in favor of Chapter 2.
1.1 CELL BASICS
This section describes the basic concepts of eukaryotic cells, which compose all multicellular organisms, such as humans, animals, and plants. Alternatively, single‐celled microorganisms such as bacteria are referred to as prokaryotes. Different viruses infect different types of cells. As discussed above, Chapter 2 further examines how viruses invade and infect human cells.
Within each eukaryotic cell is a highly complex system of organelles – the tiny cellular structures that perform specific functions within the cell. These structures keep the cell running, much like organs do in the human body. Several key organelles are shown below in Figure 1.1.
Figure 1.1 Illustration of organelles within a cell.
Source: National Cancer Institute/U.S. Department of Health and Human Services/Public Domain.
(Louten 2016)
The following subsections below highlight a few organelles that play a crucial role during virus invasion leading to infection. These include the cytoplasm, ribosomes, and nucleus.
1.1.1 CYTOPLASM
The cytoplasm is one of the most important organelles within the cell membrane since it holds the other organelles together in its gel‐like composition and allows for numerous processes to occur within the cell through the suspension of organelles and cellular molecules. Cytoplasm also allows for the occurrence of biochemical reactions within the cell, such as the replication of RNA viruses and protein synthesis (Denison 2008). The replication of RNA viruses occurs here in the cytoplasm as a majority of the enzymes used to replicate RNA are virally encoded.
1.1.2 RIBOSOMES
Ribosomes found in the cytosol play an important role in the manufacture of proteins within the cell. These ribosomes are located not only attached to the rough endoplasmic reticulum (rER), but also floating within the cytosol. The ribosomes attached to the endoplasmic reticulum have the ability to create proteins. Once transferred to the lumen, proteins are modified to be utilized by the remaining organelles throughout the cell. This is all possible due to the binding of the ribosomes to the messenger RNA (mRNA) prior to the production of proteins (Louten 2016). Viruses have the ability to overtake the production of these proteins by the ribosomes for their own use.
1.1.3 NUCLEUS
The nucleus within eukaryotic cells contains organelles necessary for the regulation of cellular activities as well as the structures that contain the cell's DNA and other hereditary information. These structures inside the nucleus are comprised of chromosomes, the nuclear matrix, nucleoli, the nucleoplasm, the outer and inner nuclear membranes as well as the nuclear pores (Louten 2016).
The nucleus also allows for the replication of DNA which is then transcribed into messenger RNA to be used throughout the cell. Because of this, viruses must be able to have access to the cell's nucleus in order to replicate their DNA and attack other cells (Geer and Messersmith 2002).
1.2 CELL REPLICATION
Cell replication is a detailed process involving the copying of DNA to make new cells. DNA contains the genetic code that is present in every cell in the human body. DNA and RNA are both made up of nucleic acids, which are described below. They are critical to the process of replication and survival, not only for the cell but also for the invading virus (Denison 2008).
1.2.1 NUCLEIC ACIDS
This subsection will review the structure and function of DNA and RNA, which, as previously mentioned, are both made up of various nucleotides. Nucleotides are the basic building blocks for all living organisms, and are a crucial component in all cells. Nucleotides are comprised of three basic components:
A five‐carbon sugar molecule (deoxyribose for DNA or ribose for RNA)
A phosphate group containing phosphorus and oxygen
A
nitrogenous base
, a ringed molecule of nitrogen, oxygen, and hydrogen
There are four variations of nitrogenous bases, and together they form the basic building blocks for all living organisms: adenine (A), guanine (G), cytosine (C), and thymine (T). (Note: Uracil (U) replaces thymine in RNA) Together, these four different nucleotides combine to form polynucleotide base pairs. In DNA, adenine always pairs with thymine, while cytosine pairs with guanine. The pairs are bound together by hydrogen bonds. These base pairs form the coding sequences within the DNA double helix, as shown in Figure 1.2. (Seladi‐Schulman 2019; NIH 2010).
Figure 1.2 DNA polynucleotide base pairs with sugar‐phosphate backbone https://medlineplus.gov/genetics/understanding/basics/dna/
The double helix of DNA is structured as two complementary polynucleotide strands, with the leading strand running from the 5′ to 3′ carbon and the lagging strand running from the 3′ to 5′ carbon, as shown in the middle of Figure 1.3, below. The base pairs are located within the resulting double helix. The code, which is the order of nucleotides, determines which amino acids will be produced, and therefore, which proteins. Each amino acid is encoded by the order of three nucleotides (Geer and Messersmith 2002).
Figure 1.3 DNA Replication https://www.genome.gov/genetics-glossary/DNA-Replication
1.2.2 DNA REPLICATION
The cell cycle consists of four stages including gap 1(G1), synthesis (S Phase), gap 2(G2), and mitosis. Within these four stages, each cell has the ability to grow and divide while also replicating its DNA. The process of DNA replication occurs when the cell creates a direct copy of its chromosomes either during synthesis or during the s‐phase of the cell cycle.
As depicted in Figure 1.3, the DNA molecule is untwined during replication, and the two DNA strands are separated from one another through the presence of cellular enzymes within the cell. DNA polymerase is one of the main enzymes utilized in DNA replication due to its ability to place the complementary nucleotides of the new DNA strand in the 5′ to 3′ direction. DNA polymerase also adds in nucleotides based upon the complementary base pair rules as discussed in the previous section and is highly accurate, so there is a very low rate of misplaced nucleotides. This is shown in Figure 1.3. (Geer and Messersmith 2002).
Working alongside DNA polymerase is an enzyme known as RNA polymerase that synthesizes RNA. Similar to DNA polymerase, this enzyme uses a DNA template to produce a section of RNA that adds nucleotides in a 5′ to 3′ direction while also using the complementary base pair rule. RNA polymerase is known to have a lower rate of fidelity as compared to DNA polymerase (Louten 2016). This fact is highly relevant to virus replication, since an RNA virus tends to have more replicating errors—and as a result, more mutations than a DNA virus, as will be discussed in Chapter 2.
Another enzyme involved with DNA replication is known as primase, which is an enzyme that allows DNA polymerase to bind to a formerly single strand of DNA. Primase has the ability to form a double‐stranded segment that allows for the binding of DNA polymerase through laying a complementary fragment of RNA on top of the single strand of DNA. (Geer and Messersmith 2002).
Because DNA replication is performed in the cell's nucleus, viruses must gain entry before taking advantage of DNA polymerase and other enzymes to replicate their own genomes and divide further (Louten 2016).
1.2.3 RNA STRUCTURE AND ROLE
DNA and RNA are known to have both positive and negative strands. The positive strand of DNA is found within a single‐stranded DNA virus and is referred to as any strand that has the same base sequence as a negative DNA strand. Meanwhile, a negative strand of DNA will have a base sequence complementary to that of the positive strand. The positive strand of RNA has the same polarity as viral mRNA while also containing codon sequences, “trinucleotide sequences of DNA or RNA that correspond to a specific amino acid…” [that may be translated to viral proteins] (genome.gov). Negative RNA strands are noncoding and must be copied by RNA polymerase in order to produce mRNA that is translatable (King et al. 2014). This background information is important for understanding key characteristics of various categories of viruses, (e.g., (+) or (‐) sense DNA viruses).
DNA is able to use mRNA, transfer RNA (tRNA), and ribosomal RNA (rRNA) to replicate itself and repair mistakes during the process of replication. Messenger RNA is a single stranded temporary copy of a DNA molecule that is to be translated by the ribosome. Ribosomal RNA is known to help translate the information available in mRNA and change it into a protein to be used by the cell. The mechanism is illustrated below in Figure 1.4 below. The process of DNA replication and the transcription of DNA into mRNA occurs in the nucleus of the cell while mRNA is translated in the cell's cytosol by ribosomes, leading to the creation of a protein. RNA acts as a copy of a DNA molecules' hereditary genetic information. Ribosomes have the ability to create proteins through the use of amino acids using a sequence of nucleotides present in the RNA (Louten 2016).
Figure 1.4 Protein Synthesis: Transcription and Translation https://nci-media.cancer.gov/pdq/media/images/761782.jpg
As depicted in Figure 1.4, transcription refers to the creation of an RNA model from an original DNA sequence, while translation occurs when RNA goes through the process of being made up of nucleotides to becoming made up of proteins consisting of amino acids during the process of protein translation. These processes will be described in detail in the next subsection.
Nucleic acids have the ability to code for proteins through a series of three nucleotides that code for a specific amino acid. Because proteins are made up of amino acid chains, the nucleic acids within each amino acid directly impact each protein. mRNA of a previously known arrangement can be used to determine the amino acid sequence by directing the synthesis of a selected protein. In this manner, the genetic code could be decoded by comparing the original order of the mRNA with the synthesized proteins' amino acid sequence (Smith 2008).
1.2.4 PROTEIN SYNTHESIS
Protein synthesis is the process of creating protein strands through the use of ribosomes, mRNA, tRNA, and amino acids – mainly through transcription and translation, as shown in Figure 1.4.
Transcription occurs when a section of DNA is copied into mRNA. The template strand of the two strands of DNA is known to act as a template for transcription. RNA polymerase II is the enzyme that can synthesize DNA from that template, which is recruited to the complex by transcription factors binding to the promoter sequence. RNA polymerase II then reads the template strand of DNA using complementary base pairing rules specifically in the 3′ to 5′ direction (Louten 2016).
Translation is a three‐part process consisting of initiation, elongation, and termination. Each of these three parts, discussed below, allows for the assembly of a protein through amino acids from the ribosome (Geer and Messersmith 2002).
Initiation
This consists of a ribosome attached to a 5′ cap of mRNA transcript which then scans until a start codon is recognized. Corresponding tRNA along with a ribosomal subunit join the complex and elongation begins.
Elongation
During elongation, tRNA delivers amino acids to form a growing chain for each additional codon. Once the tRNA delivers its amino acid to the mRNA, it is then released from the ribosome and recharged by enzymes within the cell to be reused.
Termination
This third and final stage of translation occurs when the moving ribosome encounters a stop codon, causing the ribosome to leave the mRNA when the protein is released as a result.
1.3 CELLULAR TRANSPORT
Cellular transport refers to the movement of resources or supplies through the plasma membrane of the cell. There are two general categories of transport: passive and active. Passive transport does not require any energy, while active transport does require it.
1.3.1 PLASMA MEMBRANE
The plasma membrane is the main layer of separation between a cell and its surrounding environment. Because of this, the plasma membrane is the first layer of contact a virus encounters while infecting a cell. The plasma membrane is most commonly represented by the fluid mosaic model, which portrays the integral proteins as being suspended in the lipid bilayer. The lipid bilayer is composed of amphipathic phospholipid molecules that contain both a hydrophobic tail and a hydrophilic head portion. The fatty tails of the phospholipids face together when placed in an aqueous solution, while the heads will be positioned on the outside. This way, the bilayer is able to form a barrier between the inside of the cell and the extracellular environment, creating a plasma membrane sufficient for cellular activities.
Integral membrane proteins (IMPs) are located in the lipid bilayer of the cell membrane. These integral proteins are necessary for a variety of extracellular functions, and, among other functions, can act as receptors or as cellular adhesion molecules (CAMs), which are used to adhere neighboring cells to each other. In addition to integral proteins are peripheral membrane proteins located on the surface of the plasma membrane associated with intracellular activities (Louten 2016).
Integral proteins also help with transporting substances, including those such as ions and other small molecules from one side of the cell to the other. However, some of these substances may be too large to fit between the channels and carrier proteins situated in the lipid bilayer and must be exported through processes such as exocytosis – a form of active transport out of a cell.
1.3.2 CELL SIGNALING
Also known as transduction, cell signaling is a vast network where the cell has the ability to communicate with other cells by releasing hormones and with other signaling molecules. Transduction would not be possible without the signal‐transduction pathway, which allows for signals to be transmitted throughout the cell and results in a cellular response (Nair et al. 2019).
In order to communicate successfully with other cells, messages are first transferred from the ligand (a molecule that binds to a receptor) to the appropriate receptor, then decoded through a series of reactions of second messengers otherwise known as ions, kinases, and other small molecules. Afterward, the same message travels to the nucleus from the cell membrane, where several processes occur, including gene expressions, subsequent translations, as well as protein targeting. These processes target both the cell membrane and other organelles, all from the original message communicated. An intermediate is formed by a combination of intracellular signaling. This process is initiated by the response brought to the cell's ligands.
The process of cell signaling has the ability to control various multicellular activities including cell growth, differentiation, and other cell‐specific functionalities. Due to this variability, signaling can be used in multiple areas, including endocrine, paracrine, juxtracrine, autocrine, and in neuronal neurotransmission. In addition to the various signals, the chemical makeup of the ligands is also differentiated in the inclusion of smaller molecules such as lipids, nucleic acids, and proteins, among others (Nair et al. 2019).
1.4 IMMUNE DEFENSE
The human body has various ways to defend itself against assault from infectious diseases and toxins. The immune system has the ability to determine the difference between “self” and “foreign” elements, and to mount an effective immune defense by acting against all “foreign” invaders. There are different protective mechanisms at the body's disposal, consisting of innate and adaptive immunity, both of which are explained below.
1.4.1 INNATE IMMUNITY
The innate immune system acts against all nonspecific invaders such as antigens and other harmful microorganisms rather than just attacking any one specific infectious microparasite. This nonspecific protective mechanism consists of three separate components: physical barriers, the inflammatory response, and phagocytosis.
Physical (and chemical) barriers that act as the body's primary line of defense are surrounded by epithelia. Epithelial surfaces have the ability to separate the body from pathogens present in the external environment and consist of the skin, respiratory and urogenital tracts, as well as the mucus membranes. When these barriers are penetrated by invaders and pathogens enter the body, an immune response occurs to rapidly eliminate the infection.
The inflammatory response occurs at the infected area of tissue injury caused by an influx of foreign invaders or from other bodily trauma. An influx of specialized cells to the injured tissue results in an inflammatory reaction leading to a release of chemicals. These specialized phagocytic cells, known as macrophages, have the ability to isolate and identify invasive cells while releasing active molecules. The surrounding capillaries then dilate as a result of the released inflammatory cytokines, which then increases blood flow, eventually causing fluid leakage that accounts for the side effects of inflammation. These effects may include swelling, redness, and pain.
Phagocytosis, the last step in innate immunity, is used to engulf and digest cells as a form of receptor‐mediated endocytosis. This phase is oftentimes referred to as the cleansing or “healing” phase as it is where the inflammatory response is diminished, and the side effects of inflammation are reduced. Phagocytosis plays a role in protecting the body against viruses as macrophages and other specialized phagocytic cells help to digest bacteria and dead cells in an effort to defend against pathogens and other harmful microorganisms. In some instances, however, certain viruses are able to gain entry and take over a cell through phagocytosis.
1.4.2 ADAPTIVE IMMUNITY
Adaptive immunity is a specific protective mechanism that has two main components and five important characteristics. As compared to innate immunity, adaptive immunity allows the body to recognize and identify specific antigens and pathogens while also retaining their genetic information for future attacks. Because this immunity can recognize specific antigens, it activates lymphocytes (a type of white blood cell) with a plan of attack unique to that antigen. As a result, the humeral and the cell‐mediated immune responses—the two main components of adaptive immunity—are put into place. Both these responses are discussed below.
1.4.2.1 Humoral Immunity
The humoral immune response mainly corresponds with the function of B cells and their production of immunoglobulins, or antigen‐specific antibodies. Immunoglobulins are a type of antigen receptors found on B cells, and each immunoglobulin is only able to identify a single antibody. Because of this, the immune system contains a variety of antigens in order to create a successful defense against the wide array of pathogens and other foreign invaders the immune system encounters on a daily basis.
B cells have the ability to produce more cells with their particular antibodies when they identify and collide with their specific, corresponding antigens. Several of the new B cells created from this collision will transform into plasma cells, which are known to produce a high quantity of antibodies. The main function of these antibodies within the process of adaptive immunity is to bind with extracellular pathogens present in the blood or other bodily fluids.
1.4.2.2 Cellular Immunity
In addition to the humoral aspect of adaptive immunity is the cell‐mediated immune response. Rather than relying on the function of B cells, cellular adaptive immunity focuses more on the work of T cells within the body in response to foreign invaders and potentially harmful substances. Much like B cells, T cells also have the ability to recognize antigens; however, their receptors are able to identify a large number of antigens through their similarities to immunoglobulins. B cells are only able to recognize one specific antigen.
Unlike B cells, T cells are only able to identify and attack an antigen or other harmful cell after it has already been processed by particular “antigen‐presenting” cells such as macrophages. After the cell is processed, antigens on the cell's surface bind to the T‐cell receptor, which then signals the T‐cell to grow and divide while also going through cellular differentiation. The activated T cells are now able to travel to the site where the antigen entered the body and release cytokines – small proteins involved in the inflammatory process – while working together with other T cells, B cells, and phagocytic cells to rid the body of infectious invaders. Cytokines or “chemical messengers” are generated by a variety of cells and can have many different functions including initiating cellular activities and processes.
The above two immune systems work together to successfully eliminate and protect the body from foreign material and pathogenic invaders. Both adaptive and innate immunity are able to initiate the body's immune response, prompting the release and activation of lymphocytes – the inflammatory response and phagocytosis among other methods to eliminate the attacking antigens and to prepare the body for future invasions of hazardous microorganisms.
1.5 APPLICATIONS
The following four illustrative examples are intended to complement the above material and to provide a better understanding of the aspects discussed within the chapter.
Illustrative Example 1.1 CYTOKINES
Examine the role of cytokines in inflammation.
Solution
There are many types of cytokines produced by the body under stress or injury. The common inflammatory response induces heat, redness, swelling, and pain, as well as impaired function. The majority of cytokines are formed by activated macrophages and T cells. Some are proinflammatory, such as IL‐1β, IL‐6, and TNF‐α, while others are activated in order to counteract the inflammatory process. Anti‐inflammatory cytokines include IL‐4 and IL‐10, among others.
Illustrative Example 1.2 RNA
Describe the functions of mRNA, tRNA, and rRNA.
Solution
While there are other types of RNA, the main three are:
Messenger RNA (mRNA), which is transcribed directly from DNA, goes on to produce proteins with the help of tRNA.
Transfer RNA (tRNA) transcribes mRNA into proteins.
Ribosomal RNA (rRNA) forms ribosomes, and are, therefore, critical for the synthesis of proteins.
Illustrative Example 1.3 LYMPHOCYTES
Explain the role of lymphocytes in adaptive immunity.
Solution
The lymphocytes are a part of the lymphoid system and are composed of B and T cells. The adaptive immune system is activated from these lymphocytes, and pathogens and other foreign invaders are disposed of before entering the bloodstream. The activation of large numbers of lymphocytes can occur as a result of antigen recognition, and the activated lymphocytes will have specified roles against particular antigens. This specific immunity can be seen in the humoral and cell‐mediated immune responses against pathogens.
Illustrative Example 1.4 TRANSLATION AND TRANSCRIPTION
Differentiate between translation and transcription in protein synthesis.
Solution
Translation accounts for the assembly of a protein through amino acids from the ribosome, and is composed of three parts, including initiation, elongation, and termination. Through the use of these three processes, translation is able to assemble a protein made up of an amino acid sequence from RNA in the cell's ribosome. Meanwhile, transcription in protein synthesis takes place when mRNA is produced through the copying of a DNA section.
1.6 CHAPTER SUMMARY
A highly complex system of organelles is present within each eukaryotic cell.
One of the most important organelles is the cytoplasm, which has the ability to secure the organelles together, while also being the area many cellular processes occur by suspending other organelles and molecules in its characteristic gel‐like composition.
When DNA replication occurs, the cell is able to create a direct replicate copy of itself and its chromosomes during synthesis of the cell cycle.
Protein synthesis utilizes mRNA and tRNA in addition to amino acids and ribosomes when creating protein strands through transcription and translation.
The main layer of separation between cells and the outside extracellular environment is the plasma membrane, which also acts as the first layer of contact encountered by a virus or foreign invader when infecting a cell.
Transduction, or cell signaling, has the ability to facilitate multiple processes such as the communication between cells.
The immune system acts against all foreign invaders in different protective mechanisms consisting of innate and active immunity.
1.7 PROBLEMS
How many antigens are B cells able to recognize?
What are immunoglobulins? Cytokines?
When identifying nonspecific foreign invaders, which immunity is used?
How many nucleotides is each amino acid encoded by?
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2Basics of Virology
CHAPTER MENU
Viral Basics and Terminology
Viral Life Cycle
Virus Structure and Classification
Viruses in Context of the Tree of Life
Viral Genetics
Applications
Chapter Summary
Problems
References
Viruses that cause death and disease, such as Smallpox, Ebola, and HIV, are well known and have played a significant role in human history. At the time of this writing, the world is contending with just such a virus in SARS‐CoV‐2, the virus that causes COVID‐19. The aim of this chapter is to explain what exactly defines a virus and to demonstrate the unique place viruses hold in the universe.
The chapter will also review classification, definitions, and the viral characteristics that allow them to invade cells and self‐replicate. As was discussed, viruses are composed of nucleic acids, either DNA (deoxyribonucleic acid) or RNA (ribonucleic acid). Some background information about these basic genetic materials is vital to understanding how viruses behave. The reader is referred to Chapter 1: Overview of Molecular Biology, for a review of what nucleic acids are, how they function and maintain cells, and how they facilitate cellular reproduction.
2.1 VIRAL BASICS AND TERMINOLOGY
Viruses are complex biochemical entities often regarded as nonliving and are therefore classified separately from the nomenclature used to describe all living organisms. All viruses contain genetic material in the form of either DNA or RNA, but never both. Although they contain the same genetic material that exists in cells, viruses are not themselves cellular. Importantly, they can only replicate inside living cells, or host cells, which means that they must invade and commandeer a host cell to make it work for them. Unlike cells, they do not replicate in a binary fashion but instead rapidly multiply and self‐assemble within the invaded cell and can release thousands of copies at the same time, often by lysing—thus destroying—the cell. The host cell can be a single‐celled bacteria or a cell within a eukaryote—a multi‐cellular organism—such as a plant, animal, or human (Taylor 2014, pp. 23–24).
A virus's nucleic acid core is its genome—genetic material—which is either DNA or RNA. This nucleic acid can be single‐ or double‐stranded. It is possible for the genome to be monopartite, with all genes based on one nucleic acid molecule, or segmented, and distributed among multiple nucleic acid molecules (Burrell and Howard 2017, p. 30). The core is surrounded by a capsid, which is a protein barrier layer that protects the genetic material while also allowing the virus to attach to the host cell. Together, the genome and capsid are referred to as the neocapsid. In addition, some viruses also contain an outer envelope, an extra outer layer comprised of a lipid bilayer and surface proteins, which further aid in attaching to specific cells. The envelope is often originally derived from the membrane of a host cell, which was acquired upon the virus's exit. Envelopes perform various functions, including the facilitation of binding to the receptors of the target cell, and membrane fusion. In addition, since the envelope is cell‐derived, it may serve to help the virus to evade the host's immune system while it searches for more cells to invade (Baron 1996; Burrell et al. 2017, pp. 36).
Virions are defined as complete virus particles with full infectivity. As noted, virus particles are only active once inside a host cell. This inactive state allows for protection from the external environment and facilitates the discovery of new host cells. The virion contains the neocapsid along with any enzymes needed for replication and any proteins on its surface that aid in the attachment process, which will be explained below.
There are various ways to classify viruses, and the most basic grouping is centered simply on which genetic material they contain, either DNA or RNA. While cells have double‐stranded DNA and single‐stranded RNA, viruses can contain either double‐stranded or single‐stranded versions of either DNA or RNA. This categorization helps to predict some basic traits within groups, such as higher degree of mutations in RNA viruses due to the lack of proofreading within the cell.
2.2 VIRAL LIFE CYCLE
Since virions only become active once they find a cell to invade, the virus life cycle is generally considered to begin with attachment to the host cell and to end with the destruction of that cell. When the host cell is destroyed, new virion copies are released into the extracellular environment. These virions are then free to continue the cycle by attacking nearby cells (Taylor 2014). The stages of viral replication are listed here and further explained in the subsections below (Louten 2016),
Attachment (Cell Connection)
Penetration (Cell Entry)
Uncoating
Replication
Assembly
Maturation
Release
These stages are also depicted in Figures 2.1 and 2.2:
Figure 2.1 Cell Connection and Entry. (Source: https://www.genome.gov/about-genomics/fact-sheets/Genomics-and-Virology.)
Figure 2.2 Virus Replication and Release. (Source: Adapted from: https://www.genome.gov/about-genomics/fact-sheets/Genomics-and-Virology.)
2.2.1 ATTACHMENT (CONNECTION)
Prior to infection, the virion must enter the cell. The first stage is attachment, when the virus uses the host's own surface proteins against it. In the cell's normal functioning, these proteins serve to transport ions and molecules across the phospholipid membrane for use within the cell. The surface proteins often serve as receptors for inbound proteins (Louten 2016). The viral surface proteins, or anti‐receptors, mimic those specific proteins the cell would recognize, giving the virus access to the receptor sites for entry (Roizman 1996).
2.2.2 PENETRATION (ENTRY)
Upon successful attachment, the virus must enter the cell by crossing through the cell plasma membrane. This could occur in a few ways, including:
Entry by Direct Fusion
This method is available only to enveloped viruses, where the envelope fuses directly with the membrane, leaving the virus within the cell wall without its envelope, but with its capsid intact.
Receptor‐Mediated Endocytosis
A majority of viruses, whether enveloped or not, rely on the cell to initiate entry by endocytosis. After bonding with the receptor on the cell surface, a virion–receptor complex is formed. The cell instantly responds, engulfing the complex in a vesicle coated with substances that can withstand the difficult trip through the membrane of the cell. (Ryu 2017).
2.2.3 UNCOATING
In the uncoating stage, the capsid—and envelope if it remains—is stripped away so that the virus genome can be exposed once it reaches its destination. Some viruses remain in the cell's cytoplasm and replicate from there (Louten 2016).
For the many viruses that replicate inside the cell nucleus, they must first cross through pores in the nuclear envelope prior to any gene expression. Some viruses are small enough to cross with their capsids intact. Larger viruses are usually able to attach to the surface of the nuclear envelope and then inject their genome into the nucleus (Ryu 2017).
2.2.4 REPLICATION
All viruses rely, to some extent, on their host for the ability to replicate, but the dependence varies widely. For all viruses, the main obstacle to replicating is that they do not carry ribosomes. This means that the virus must instead produce a readable messenger RNA (mRNA) code for the host to translate via ribosomal proteins and RNA (rRNA), and then synthesize those into the necessary viral proteins during replication. The details of how viruses arrive at that point is specific to individual viral families and classes and will be further discussed in Section 2.3. For further explanation on the various types of RNA, the reader is referred to Chapter 1: Overview of Molecular Biology (Ryu 2017; Li 2019).
2.2.5 ASSEMBLY
Once the correct viral proteins have been produced and transported to the target location, these newly replicated viral proteins come together to form the initial stages of a virion. Two often‐simultaneous phases of assembly take place. One is genome packaging, and the other is capsid assemblage (Ryu 2017; Louten 2016).
2.2.6 MATURATION AND RELEASE
Maturation is the final stage before the virus becomes infectious. The virus undergoes changes to its capsid structure, often making itself more chemically and physically stable and capable of withstanding temperature fluctuations, for example.
