Virology: Overview

Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. The replication cycle differs between viruses that infect bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview (bacteriophages) and viruses that infect eukaryotic Eukaryotic Eukaryotes can be single-celled or multicellular organisms and include plants, animals, fungi, and protozoa. Eukaryotic cells contain a well-organized nucleus contained by a membrane, along with other membrane-bound organelles. Cell Types: Eukaryotic versus Prokaryotic cells. Bacteriophages have either a lytic or lysogenic replication cycle, while eukaryotic Eukaryotic Eukaryotes can be single-celled or multicellular organisms and include plants, animals, fungi, and protozoa. Eukaryotic cells contain a well-organized nucleus contained by a membrane, along with other membrane-bound organelles. Cell Types: Eukaryotic versus Prokaryotic viruses have a defined 6-step replication process.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Definition

Viruses are infectious, obligate intracellular parasites, composed of a nucleic acid core (deoxyribonucleic acid ( DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure) or ribonucleic acid ( RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure)) surrounded by a protein capsid; at times, viruses are also surrounded by an envelope derived from host cell membranes.

Types of viruses

Variety of viruses in existence, including size and morphology

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Structure

Basic structure consists of: 

  • Inner “machinery” that allows the virus to replicate within host cells 
  • Outer structural component that allows the virus to survive in the environment and bind to host cells
Anatomy of a virus

Anatomy of a virus

Image: “Anatomy of a virus” by DEXi. License: CC0.

Inner components

  • Viral genome (nucleoid): diverse, composed of either RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure or DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure
  • Viral enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes: required for viral replication within the host cell:
    • DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure-dependent RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure polymerase
    • RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure-dependent RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure polymerase
    • RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure-dependent DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure polymerase (reverse transcriptase)

Outer components

  • Capsid:
    • Single- or double-layer protein shell that surrounds the nucleoid
    • Arranged of subunits, known as capsomers
    • 3 structural patterns:
      • Icosahedral
      • Helical
      • Complex
  • Envelope:
    • May or not be present
    • Surrounds nucleocapsid
    • Composed of virus-specific proteins, lipids, and carbohydrates Carbohydrates Carbohydrates are one of the 3 macronutrients, along with fats and proteins, serving as a source of energy to the body. These biomolecules store energy in the form of glycogen and starch, and play a role in defining the cellular structure (e.g., cellulose). Basics of Carbohydrates (derived from host cell membranes)
Viral capsids shapes

Viral capsids can have a (a) helical, (b) polyhedral, or (c) complex shape.

Image: “Figure 6.6”, access for free at https://openstax.org/books/microbiology/pages/1-introduction. License: CC BY 4.0.

Classification

Rna viruses flowchart classification

RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure virus identification:
Viruses can be classified in many ways. Most viruses, however, will have a genome formed by either DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure or RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure. RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure genome viruses can be further characterized by either a single- or double-stranded RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure. “Enveloped” viruses are covered by a thin coat of cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane (usually taken from the host cell). If the coat is absent, the viruses are called “naked” viruses. Viruses with single-stranded genomes are “positive-sense” viruses if the genome is directly employed as messenger RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure (mRNA), which is translated into proteins. “Negative-sense,” single-stranded viruses employ RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure dependent RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure polymerase, a viral enzyme, to transcribe their genome into messenger RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure.

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Multiple categorization schemes exist for viruses, based on physical characteristics and replication strategies.

Table: Classifications of viruses
Classification by: Types
Type and structure of nucleoid
  • DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure or RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure:
    • For RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure viruses:
      • Single-stranded (ss- RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure) genome (positive or negative sense)
      • Double-stranded (ds- RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure) genome
    • For DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure viruses: All are ds- DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure (except for Parvoviridae).
  • Linear or circular
  • Segmented or non-segmented
Structure of capsid
  • Icosahedral
  • Helical
  • Complex symmetry
Presence of envelope
  • Naked
  • Enveloped
Replication cycle (for bacteriophages)
  • Lytic
  • Lysogenic or temperate
Other
  • Host range
  • Immunologic characteristics
  • Sensitivity toward certain chemicals or physical properties

Replication

It is important to differentiate between the replication of bacteriophages (viruses that infect bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview) and eukaryotic Eukaryotic Eukaryotes can be single-celled or multicellular organisms and include plants, animals, fungi, and protozoa. Eukaryotic cells contain a well-organized nucleus contained by a membrane, along with other membrane-bound organelles. Cell Types: Eukaryotic versus Prokaryotic viruses (viruses that infect eukaryotic Eukaryotic Eukaryotes can be single-celled or multicellular organisms and include plants, animals, fungi, and protozoa. Eukaryotic cells contain a well-organized nucleus contained by a membrane, along with other membrane-bound organelles. Cell Types: Eukaryotic versus Prokaryotic cells).

Replication cycle of bacteriophages

There are 2 pathways of replication once a virus is within the bacterial host cell:

  1. Lytic cycle:
    • Occurs under conditions of DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure damage or other stresses
    • Bacteriophage takes over host cell transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription and translation Translation Translation is the process of synthesizing a protein from a messenger RNA (mRNA) transcript. This process is divided into three primary stages: initiation, elongation, and termination. Translation is catalyzed by structures known as ribosomes, which are large complexes of proteins and ribosomal RNA (rRNA). Stages and Regulation of Translation machinery (immediate and rapid phage gene and protein expression).
    • Causes lysis of bacterial host cell 
  2. Lysogenic or temperate cycle:
    • Bacteriophage genomes incorporated in bacterial host genome
    • Phage genome is then replicated in a benign, dormant state: The phage genome may be expressed when the bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview cell is stressed (e.g., nutrient depletion).

Replication cycle of eukaryotic Eukaryotic Eukaryotes can be single-celled or multicellular organisms and include plants, animals, fungi, and protozoa. Eukaryotic cells contain a well-organized nucleus contained by a membrane, along with other membrane-bound organelles. Cell Types: Eukaryotic versus Prokaryotic viruses

  • Viral genome released in infected host cell
  • Steps of viral replication:
    1. Attachment: Specialized viral proteins attach to host cell.
    2. Penetration: invasion of host cell
    3. Uncoating: capsid dismantled and genetic material made available
    4. Biosynthesis: viral nucleic acid and proteins synthesized
    5. Assembly: virions assembled within the host cell
    6. Release: via host cell lysis (for naked viruses) or the budding of the cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane (for enveloped viruses)
  • All DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure viruses replicate in the nucleus (except for the poxvirus).
  • All RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure viruses replicate in the cytoplasm (except for influenza Influenza Influenza viruses are members of the Orthomyxoviridae family and the causative organisms of influenza, a highly contagious febrile respiratory disease. There are 3 primary influenza viruses (A, B, and C) and various subtypes, which are classified based on their virulent surface antigens, hemagglutinin (HA) and neuraminidase (NA). Influenza typically presents with a fever, myalgia, headache, and symptoms of an upper respiratory infection. Influenza Viruses/Influenza and retroviruses).

Genetic Diversification

Viruses have evolved many processes to increase their genetic diversity:

  • Recombination: exchange of genes between 2 chromosomes by crossover at homologous regions
  • Reassortment:
    • Viruses with segmented genomes exchange genetic material.
    • May cause an antigenic shift (e.g., influenza Influenza Influenza viruses are members of the Orthomyxoviridae family and the causative organisms of influenza, a highly contagious febrile respiratory disease. There are 3 primary influenza viruses (A, B, and C) and various subtypes, which are classified based on their virulent surface antigens, hemagglutinin (HA) and neuraminidase (NA). Influenza typically presents with a fever, myalgia, headache, and symptoms of an upper respiratory infection. Influenza Viruses/Influenza virus)
  • Complementation:
    • Occurs when the virus has a mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations that results in a non-functional protein
    • A non-mutated virus “complements” a mutated virus (when co-infected in a host cell) by making a functional protein that serves both viruses (e.g., the hepatitis D virus Hepatitis D virus Hepatitis D virus (HDV) is a small enveloped, single-stranded RNA virus. Hepatitis D virus is considered a satellite virus, as it requires the presence of hepatitis B virus (HBV) for assembly and secretion. Therefore, in order for an individual to contract hepatitis D, coinfection or superinfection with HBV is required. Hepatitis D Virus ( HDV HDV Hepatitis D virus (HDV) is a small enveloped, single-stranded RNA virus. Hepatitis D virus is considered a satellite virus, as it requires the presence of hepatitis B virus (HBV) for assembly and secretion. Therefore, in order for an individual to contract hepatitis D, coinfection or superinfection with HBV is required. Hepatitis D Virus) requires the hepatitis B virus Hepatitis B Virus Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Hepatitis B virus is transmitted by exposure to infectious blood or body fluids. Examples of types of exposure include sexual intercourse, IV drug use, and childbirth. Hepatitis B Virus ( HBV HBV Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Hepatitis B virus is transmitted by exposure to infectious blood or body fluids. Examples of types of exposure include sexual intercourse, IV drug use, and childbirth. Hepatitis B Virus) to supply HBsAg (a key envelope protein for HDV HDV Hepatitis D virus (HDV) is a small enveloped, single-stranded RNA virus. Hepatitis D virus is considered a satellite virus, as it requires the presence of hepatitis B virus (HBV) for assembly and secretion. Therefore, in order for an individual to contract hepatitis D, coinfection or superinfection with HBV is required. Hepatitis D Virus)).
  • Phenotypic mixing:
    • Simultaneous infection of host cell with 2 viruses
    • Usually involves the mixing of the genome of 1 virus with surface proteins of the 2nd virus
Viruses genetic diversification

Viruses have evolved diverse strategies for increasing genetic diversity including recombination (the exchange of genes between 2 chromosomes by crossover at homologous regions), reassortment (exchange of segments of chromosomes), complementation (the exchange of genetic material from a functional virus with a nonfunctional virus to convert the latter into functional) and phenotypic mixing (mixing of 2 viral genomes a simultaneously infected host cell giving rise to progeny with blended genomes).

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Special Cases

Retroviruses

  • RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure viruses 
  • Contain reverse transcriptase ( RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure-dependent DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure polymerase)
  • Most prominent retrovirus is the human immunodeficiency virus (HIV).

Prions

  • Not technically viruses
  • Infectious proteins that do not contain a nucleoid
  • Cause transmissible spongiform encephalopathies Transmissible Spongiform Encephalopathies Transmissible spongiform encephalopathies (TSEs) are diseases caused by prions. Prions differ from viruses in that they are small, infectious pathogens that do not contain nucleic acid. Recognized TSEs include Creutzfeldt-Jakob Disease (CJD), variant Creutzfeldt-Jakob Disease (vCJD), Kuru, fatal familial insomnia (FFI), and Gerstmann-Straussler syndrome (GSS). Transmissible Spongiform Encephalopathies:
    • Creutzfeldt-Jakob disease 
    • Kuru
    • Bovine spongiform encephalopathy (“mad cow” disease)

References

  1. Baron, S. (1996). Medical microbiology. University of Texas Medical Branch at Galveston. https://www.ncbi.nlm.nih.gov/books/NBK7627/
  2. Parker, N., Schneegurt, M., Thi Tu, A.H., Lister, P., & Forster, B. Microbiology. (2016). Chapter 6.2, The Viral Life Cycle. https://openstax.org/details/books/microbiology

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