
A Guide to Virology for Engineers and Applied Scientists
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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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Persons
Megan M. Reynolds, BSChE, MS, MBA, is a freelance medical writer and editor with a focus on infectious diseases. She holds degrees in chemical engineering, international business, and medicine, and has more than 12 years' experience in the pharmaceutical industry in a variety of capacities.
Louis Theodore, MChE, EngScD, is a retired professor of chemical engineering with over 50 years' education experience. He has authored numerous publications and has served as section editor to the last four editions of Perry's Chemical Engineer's Handbook. Dr. Theodore currently works as an environmental engineering consultant.
Content
Preface xvii
About the Authors xix
Part I Introduction to Viruses 1
1 Overview of Molecular Biology 3
Contributing Author: Sarah Forster
1.1 Cell Basics 4
1.1.1 Cytoplasm 5
1.1.2 Ribosomes 5
1.1.3 Nucleus 6
1.2 Cell Replication 6
1.2.1 Nucleic Acids 6
1.2.2 DNA Replication 7
1.2.3 RNA Structure and Role 9
1.2.4 Protein Synthesis 9
1.3 Cellular Transport 11
1.3.1 Plasma Membrane 11
1.3.2 Cell Signaling 11
1.4 Immune Defense 12
1.4.1 Innate Immunity 12
1.4.2 Adaptive Immunity 13
1.4.2.1 Humoral Immunity 13
1.4.2.2 Cellular Immunity 14
1.5 Applications 14
1.6 Chapter Summary 16
1.7 Problems 16
References 16
2 Basics of Virology 19
2.1 Viral Basics and Terminology 19
2.2 Viral Life Cycle 21
2.2.1 Attachment (Connection) 21
2.2.2 Penetration (Entry) 22
2.2.3 Uncoating 22
2.2.4 Replication 23
2.2.5 Assembly 23
2.2.6 Maturation and Release 23
2.3 Virus Structure and Classification 24
2.3.1 DNA Viruses 25
2.3.2 RNA Viruses 25
2.3.3 Reverse Transcription Viruses (Retroviruses) 27
2.4 Viruses in Context of the Tree of Life 27
2.5 Viral Genetics 28
2.5.1 Antigenic Shift 28
2.5.2 Antigenic Drift 29
2.5.3 Phenotypic Mixing 29
2.5.4 Complementation 29
2.6 Applications 29
2.7 Chapter Summary 31
2.8 Problems 31
References 32
3 Pandemics, Epidemics, and Outbreaks 33
3.1 Human Viral Diseases 34
3.2 Ebola and Marburg Viruses 35
3.2.1 Symptoms 36
3.2.2 Diagnosis 37
3.2.3 Prevention and Treatment 37
3.3 Human Immunodeficiency Disease (HIV) 38
3.3.1 HIV Symptoms 39
3.3.1.1 Stage 1: Acute Infection 39
3.3.1.2 Stage 2: Chronic HIV Infection (Latent Phase) 39
3.3.1.3 Stage 3: Acquired Immunodeficiency Syndrome (AIDS) 39
3.3.2 Diagnosis 40
3.3.3 HIV Prevention and Treatment 40
3.4 Influenza 41
3.4.1 Influenza Symptoms 41
3.4.2 Influenza Diagnosis 42
3.4.3 Influenza Prevention and Treatment 42
3.4.4 Influenza Pandemics 43
3.5 Coronaviruses 44
3.5.1 Symptoms 45
3.5.1.1 Typical Acute Symptoms 45
3.5.1.2 Post-COVID Conditions 46
3.5.1.3 COVID-19 Multiorgan System Effects (MIS) 46
3.5.2 COVID-19 Diagnosis 47
3.5.3 COVID-19 Prevention and treatment 48
3.6 Current and Emerging Viral Threats 48
3.7 Applications 51
3.8 Chapter Summary 52
3.9 Problems 53
References 53
4 Virus Prevention, Diagnosis, and Treatment 57
4.1 Vaccination Successes and Challenges 58
4.2 Current Vaccine Technology 59
4.2.1 Live-attenuated vaccines 60
4.2.2 Inactivated vaccines 61
4.2.3 Recombinant Subunit Vaccines 61
4.2.4 Viral Vector Vaccines 62
4.2.5 Messenger RNA (mRNA) Vaccines 62
4.3 U.S.-Approved Vaccines and Requirements 63
4.3.1 Commercially Available Viral Vaccines 63
4.3.2 Vaccination Requirements 63
4.4 Viral Testing and Diagnosis 64
4.4.1 Viral Testing 65
4.4.2 Antibody Testing 66
4.5 Antiviral Treatment Options 66
4.5.1 HIV 67
4.5.1.1 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) 67
4.5.1.2 Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) 67
4.5.1.3 Protease Inhibitors (PIs) 67
4.5.1.4 Fusion Inhibitors (FIs) 67
4.5.1.5 Integrase Strand Transfer Inhibitors (INSTIs) 67
4.5.1.6 CCR5 Antagonists 67
4.5.1.7 Attachment Inhibitors 68
4.5.1.8 Post-Attachment Inhibitors 68
4.5.1.9 Pharmacokinetic Enhancers 68
4.5.2 Influenza 68
4.5.3 Hepatitis C virus (HCV) 68
4.5.4 Other Treatment Options 69
4.6 Applications 70
4.7 Chapter Summary 71
4.8 Problems 72
References 72
5 Safety Protocols and Personal Protection Equipment 75
Contributing Author: Emma Parente
5.1 Regulations and Oversight of Safety Protocols 76
5.2 Protective and Safety Systems 76
5.2.1 Personal Protective Devices and Practices 76
5.2.2 Antimicrobial Suppression And Eradication 77
5.3 Disinfection Categories and Procedures 78
5.4 Occupational Health and Safety Administration Hazmat Regulations 79
5.4.1 HAZMAT Level A Protection 80
5.4.2 HAZMAT Level B Protection 81
5.4.3 Level C Protection 82
5.4.4 Level D Protection 83
5.5 Bio Level Safety and Security 83
5.6 COVID-Related Safety Precautions 84
5.6.1 Personal Protective Equipment 84
5.6.2 Transmission Control 85
5.7 Applications 85
5.8 Summary 87
5.9 Problems 87
References 88
6 Epidemiology and Virus Transmission 91
6.1 Overview of Epidemiology 92
6.2 Government Agencies' Contributions to Public Health 94
6.2.1 The Role of the Centers for Disease Control and Prevention (CDC) 94
6.2.2 The World Health Organization (WHO): Successes and Challenges 95
6.3 Epidemiologic Study Design 96
6.3.1 Outbreak Case Example 98
6.3.2 Clinical Trials 99
6.4 Virus Transmission 100
6.4.1 Modes of Transmission 101
6.5 Applications 102
6.6 Chapter Summary 104
6.7 Problems 105
References 105
Part II Practical and Technical Considerations 109
7 Engineering Principles and Fundamentals 111
Contributing Author: Vishal Bhatty
7.1 History of Engineering 112
7.2 Problem Solving: The Engineering Approach 113
7.2.1 Problem-Solving Methodology 114
7.2.2 Engineering and Scientific Sources 115
7.3 Units and Conversion Constants 115
7.3.1 The Metric System 115
7.3.2 The SI System 117
7.4 Dimensional Analysis 117
7.5 Process Variables 119
7.6 The Conservation Laws 121
7.7 Thermodynamics and Kinetics 125
7.8 Applications 126
7.9 Chapter Summary 130
7.10 Problems 130
References 131
8 Legal and Regulatory Considerations 133
8.1 The Regulatory System 134
8.1.1 Laws, Regulations, Plans and policy: The Differences 135
8.1.2 Policies and Plans 137
8.2 The Role of Individual States 138
8.3 Key Government Agencies 140
8.3.1 Environmental Protection Agency (EPA) 140
8.3.2 Centers for Disease Control and Prevention (CDC) 141
8.3.3 Food and Drug Administration (FDA) 141
8.3.4 Occupational Health and Safety Administration (OSHA) 141
8.3.5 Legal Considerations during a Public Health Crisis 142
8.4 Public Health Emergency Declarations 143
8.5 Key Environmental Acts 145
8.6 The Clean Air Act 145
8.7 Regulation of Toxic Substances 147
8.7.1 Toxic Water Pollutants: Control and Classification 150
8.7.2 Drinking Water 150
8.7.3 Surface Water Treatment Rules (SWTR) 151
8.8 Regulations Governing Infectious Diseases 153
8.8.1 Vaccination Laws 155
8.8.2 State Healthcare Worker and Patient Vaccination Laws 155
8.8.3 State-Mandated Childhood Vaccinations 155
8.9 Applications 155
8.10 Chapter Summary 159
8.11 Problems 159
References 160
9 Emergency Planning and Response 163
9.1 The Importance of Emergency Planning and Response 164
9.2 Planning for Emergencies 166
9.2.1 Preparedness Training 166
9.3 Plan Implementation 167
9.3.1 Notification of Public and Regulatory Officials 168
9.4 EP&R for Epidemics and Pandemics 169
9.4.1 Federal Public Health and Medical Emergency Preparedness 170
9.4.2 Emergency Operations Center 170
9.4.3 Disease Containment 172
9.4.4 Public Notification of Pandemic Quarantines and Lockdowns 173
9.4.5 The National Strategy for Pandemic Influenza (NSPI) 173
9.5 EP&R for Industrial Accidents 174
9.5.1 Emergency Planning and Community Right-to-Know Act (epcra) 175
9.5.2 The Planning Committee 177
9.6 EP&R for Natural Disasters 179
9.7 Current and Future Trends 181
9.8 Applications 181
9.9 Chapter Summary 184
9.10 Problems 184
References 185
10 Ethical Considerations within Virology 189
Contributing Author: Paul DiGaetano, Jr.
10.1 Core Ethics Principles 190
10.2 Important Tenets of Ethical Research 191
10.2.1 Conducting Research During a Health Crisis 192
10.2.2 Scientific Cooperation During a Health Crisis 192
10.2.3 Fair and Ethical Study Design and Implementation 193
10.3 Ethical Dilemmas in Public Health 193
10.3.1 Public Health Surveillance 193
10.3.2 Ethical Evaluation of Nonpharmaceutical Interventions 195
10.3.3 Ethical Consideration Involving Restrictions of Movement 197
10.4 Ethical Considerations Regarding Medical Interventions 199
10.4.1 Emergency Use Of Medical Interventions 200
10.5 Applications 201
10.6 Chapter Summary 202
10.7 Problems 203
References 203
11 Health and Hazard Risk Assessment 205
11.1 Introduction to Risk Assessment 207
11.2 The Health Risk Assessment Process 209
11.3 Dose-Response Assessment 211
11.4 The Hazard Risk Assessment Process 213
11.5 Hazard Risk Versus Health Risk 214
11.5.1 Health Risk Assessment (HRA) Example 215
11.5.2 Hazard Risk Assessment (HRZA) Example 215
11.6 COVID-19 Pandemic Hazard Risk 216
11.7 The Uncertainty Factor 217
11.8 Applications 218
11.9 Chapter Summary 220
11.10 Problems 220
References 221
Part III Engineering Considerations 223
12 Introduction to Mathematical Methods 225
Contributing Author: Julian Theodore
12.1 Differentiation 226
12.2 Integration 228
12.2.1 The Trapezoidal Rule 228
12.2.2 Simpson's Rule 229
12.3 Simultaneous Linear Algebraic Equations 230
12.3.1 Gauss-Jordan Reduction 231
12.3.2 Gauss Elimination 232
12.3.3 Gauss-Seidel Approach 232
12.4 Nonlinear Algebraic Equations 233
12.5 Ordinary Differential Equations 234
12.6 Partial Differential Equations 237
12.7 Applications 237
12.8 Chapter Summary 240
12.9 Problems 240
References 241
13 Probability and Statistical Principles 243
13.1 Probability Definitions and Interpretations 244
13.2 Introduction to Probability Distributions 246
13.3 Discrete Probability Distributions 247
13.3.1 The Binomial Distribution 248
13.3.2 Multinomial Distribution 248
13.3.3 Hypergeometric Distribution 249
13.3.4 Poisson Distribution 250
13.4 Continuous Probability Distributions 250
13.4.1 Measures of Central Tendency and Scatter 251
13.4.2 The Normal Distribution 252
13.4.3 The Lognormal Distribution 256
13.4.4 The Exponential Distribution 257
13.4.5 The Weibull Distribution 258
13.5 Contemporary Statistics 259
13.5.1 Confidence Intervals for Means 260
13.5.2 Confidence Intervals for Proportions 260
13.5.3 Hypothesis Testing 261
13.5.4 Hypothesis Test for Means and Proportions 261
13.5.5 The F Distribution 262
13.5.6 Analysis of Variance (ANOVA) 262
13.5.7 Nonparametric Tests 264
13.6 Applications 264
13.7 Chapter Summary 268
13.8 Problems 268
References 269
14 Linear Regression 271
14.1 Rectangular Coordinates 272
14.2 Logarithmic Coordinates 273
14.3 Methods of Plotting Data 275
14.4 Scatter Diagrams 275
14.5 Curve Fitting 278
14.6 Method of Least Squares 280
14.7 Applications 284
14.8 Chapter Summary 287
14.9 Problems 288
References 288
15 Ventilation 289
15.1 Introduction to Industrial Ventilation Systems 290
15.2 Components of Ventilation Systems 291
15.3 Fans, Valves and Fittings, and Ductwork 293
15.3.1 Fans 293
15.3.2 Valves and Fittings 295
15.4 Selecting Ventilation Systems 296
15.5 Key Process Equations 298
15.5.1 Regarding Friction Losses 299
15.6 Ventilation Models 300
15.7 Model Limitations 302
15.8 Infection Control Implications 303
15.9 Applications 305
15.10 Chapter Summary 309
15.11 Problems 310
References 310
16 Pandemic Health Data Modeling 313
16.1 COVID-19: A Rude Awakening 315
16.2 Earlier Work 316
16.3 Planning for Pandemics 318
16.4 Generating Mathematical Models 319
16.5 Pandemic Health Data Models 324
16.6 In Review 329
16.7 Applications 331
16.8 Chapter Summary 338
16.9 Problems 338
References 339
17 Optimization Procedures 341
17.1 The History of Optimization 342
17.2 The Scope of Optimization 344
17.3 Conventional Optimization Procedures 346
17.4 Analytical Fomulation of the Optimum 347
17.5 Contemporary Optimization: Concepts in Linear Programming 350
17.6 Applied Concepts in Linear Programming 351
17.7 Applications 355
17.8 Chapter Summary 357
17.9 Problems 358
References 359
Index 361
1
Overview 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...
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