General virology

Summary

A virus is an obligate intracellular parasite, meaning that it can only survive within a host cell and depends on it for replication and metabolic processes, e.g., protein synthesis. Viruses can be classified based on their genome (DNA or RNA) or other structural components, such as the capsid, the envelope, and the viral receptor proteins (spikes). The viral replication cycle occurs within the host cell and involves attachment to and penetration of the host cell, uncoating of the nucleic acid, replication of the nucleic acid, synthesis of virus proteins, assembly of the components, and release of new viruses via budding or cell lysis. The process of nucleic acid replication differs between DNA and RNA viruses. The host body has various physical and immunological defense mechanisms to inactivate and eliminate viruses. However, some viruses have the ability to persist in a dormant state within the host's body (e.g., Herpesviridae) after an active infection has resolved. The most important diagnostic tools in virology are serological testing and nucleic acid detection. This article provides an overview of the most common enveloped and nonenveloped RNA viruses and DNA viruses. For more details regarding the individual viruses, please see the corresponding articles.

Basics of virology

Definition

  • A virus is an obligate intracellular parasite. Accordingly, it can only survive within a host cell and depends on it for replication and metabolic processes.
  • Virion: The infective form of a virus when present outside of cells, which consists of DNA or RNA, a protein capsid, and sometimes an envelope.

Structure

The most important viral components include:

Viral genome

To remember that REOvirus has a double-stranded RNA genome, think: “Double Rhymes are REOccuring all the time”

To remember the number of segments of orthomyxoviruses (INFLUENZA viruses: 8, BUNyaviruses: 3, REoviruses: 10–12, and AREnaviruses: 2), think: “A vegan INFLUENCER ate (8) 3 BUNnies and upset 10–12 REaders in 2 AREas.

Capsid

Protein coat composed of capsomeres (aggregations of protomer subunits) that encloses the genome

Envelope

Other

  • Spikes: viral receptor proteins (enables adhesion to host cell)
  • Sheath and tail fibers: present in bacteriophages

To remember the +ssRNA viruses (TOGavirus, RETRovirus, HEPevirus, PICornavirus, CAlicivirus, FLAVivirus, and CORonavirus), think “2 Golden Retrievers are Heppily Picturing Cauliflower-Flavoured Corn dogs.”

To remember the RNA viruses that are naked (Picornaviridae, Reoviridae, Caliciviridae, and Hepeviridae), think: ”Don't Run around naked, put on some PRetty ClotHes.”

To remember that ADEnovirus, PAPillomavirus, POLyomavirus, and PARvovirus are DNA viruses without an envelope, think of “Without ADEquate PAPers, the POLice will Deny PARole.”

To remember that pOXvirus, hepatitis B virus and HERpesvirus are enveloped DNA viruses, think of “A bOXer Dog will never B a HERbivore.”

Viral life cycle

Viruses replicate by synthesizing and assembling their individual components within the host cell.

  1. Attachment to the host cell: viruses use host cell surface proteins and receptors for entry (see receptors used by viruses below)
  2. Penetration into the host cell
  3. Uncoating of the nucleic acid
  4. Replication of the nucleic acid and formation of virus proteins by transcription and translation (in retroviruses, RNA is initially transcribed into DNA)
  5. Assembly of virus components
  6. Viral release
    • Enveloped viruses: released via budding
    • Nonenveloped viruses: released via host cell lysis

The period between uncoating in the host cell and production of recognizable virus particles is known as the eclipse period.

Receptors used by viruses

Viruses use host cell surface proteins and receptors to attach and penetrate the cells.

“The rhino knocked over mI CAMera”: rhinovirus enters cells via ICAM-1.

Pathogenicity

Mechanisms by which viruses cause infection in the host:

Course of viral infection

  • Abortive (no viral replication or cell damage)
  • Acute
  • Chronic
  • Persistent
    • Latent (inactive; no replication): virus remains dormant in infected cells
    • Productive (viral replication occurs, dormant infection with few or no signs of infection)
    • Transforming (virus may or may not replicate): triggers malignant transformation (e.g., EBV, HPV)

Host defense mechanisms

The body has multiple defense mechanisms to inactivate and eliminate viruses. See “Innate immune system” and “Adaptive immune system.”

Interferon can be used to treat active hepatitis B and hepatitis C.

Viral genetics

Viral genome replication

Viral genomic replication depends on the viral genome of the progenitor virus.

Viruses with DNA genomes (DNA viruses)

DNA viruses replicate in the nucleus of host cells (except Poxviridae, which carry their own DNA-dependent RNA polymerase).

To remember that HERpes, ADeno, POLyoma, POx, PARvo, HEPadna, and PAPilloma are DNA viruses, think: “I saw HER AD about a POLtergeist and POkemon PARty for HEPcats in the DAily PAPer.

Viruses with RNA genomes (RNA viruses)

RNA viruses replicate in cytoplasm of host cells (except Retroviridae and influenza viruses).

To remember thta poxvirus is the only DNA virus that replicates outside the nucleus, think: “POX, Progeny is Outside the boX.”

To remember that every RNA virus replicates in the cytoplasm (except influenza and retrovirus), think: “aRe NA-VI RUStics CYTy slickers? Yes, except if INFLUENced by RETRO fashion!”

To remember that orthomyxovirus, paramyxovirus, arenavirus, filovirus, bunyavirus, and rhabdovirus are -ssRNA viruses, think: “ORTHOpedics PARAglide into an ARENA FILled with BUNnies that have RABies.”

Viral infectivity of nonenveloped viruses

The infectivity of naked viruses is determined by the genome.

Genetic diversification

Process Mechanism
Recombination (viral)
  • Gene exchange between two chromosomes
    • Crossover between two regions of homologous base sequences
    • Results in progeny with genetic material from two parental viral strains
Reassortment (viral)
Complementation (viral)
  • Occurs in two different scenarios
    • Scenario 1: two mutated viruses from same/different family infect the same cell
    • Scenario 2
      • Mutated viral genome codes for a nonfunctional protein, a nonmutated viral genome codes for a functional protein.
      • The functional protein can be used by both mutated and nonmutated virus.
      • E.g., HBV codes for HBsAg, which is used by hepatitis D virus (HDV) as an envelope protein → HDV infection (without HBsAg, HDV cannot cause infection)
Phenotypic mixing (viral)
  • Occurs with coinfection of a cell with two related viruses (virus A and virus B) → genome of virus A is partially or completely coated by surface proteins of virus B → pseudovirion formation (viral hybrid)
    • Virus A determines genetic material of progeny viruses (including surface proteins)
    • Surface proteins from virus B determine host tropism (infectivity of the hybrid virus)
    • Future generations lose their infectivity and return to their previous state (future virions will have the coat from virus A)
Phenotypic masking (transcapsidation)
  • Related viruses infect the same cell
  • Capsid of one virus envelopes genome of another virus
Point mutations

Some viruses are DESParate: antigenic Drift → Epidemics, antigenic Shift → Pandemic.

Diagnostics

The most important diagnostic tools in virology are serological testing and nucleic acid detection. To identify specific, localized increase in viral production, different biological materials should be analyzed and compared.

Enveloped DNA viruses

Viral family Capsid Genetic structure Important examples Diseases
Herpesviridae
  • Icosahedral
  • dsDNA
  • Linear
Hepadnaviridae
  • Icosahedral
  • Partially dsDNA
  • Circular
  • Acute/chronic hepatitis B
Poxviridae
  • Complex
  • Smallpox: declared eradicated in 1980. The virus was eradicated by 1980 through widespread immunization with a live-attenuated vaccine and is no longer found outside of laboratories.

Nonenveloped DNA viruses

Viral family Capsid Genetic structure Important examples Diseases
Adenoviridae
  • Icosahedral
  • dsDNA
  • Linear
  • Adenovirus
    • More than 50 serotypes
    • Transmission via contaminated water or fecal-oral route
    • Different serotypes infect various cells
    • May persist after primary infection
Papillomaviridae
  • dsDNA
  • Circular
  • Human papillomavirus (HPV)
    • Comprised of ∼ 100 genotypes
      • Low-risk subtypes: include HPV 1, 2, 6 and 11
      • High-risk subtypes: include HPV 16, 18, 31, and 33
    • Transmission mainly via sexual intercourse
    • Persistent after primary infection
    • Active HPV vaccination recommended for individuals 9–45 years of age
Polyomaviridae
  • dsDNA
  • Circular
  • JC virus
    • Transmission usually occurs during childhood
    • Persistent after primary infection
  • BK virus
    • Airborne transmission during childhood
    • Persistent after primary infection
Parvoviridae

To remember the diseases associated with polyomaviruses, think: “JC virus leads to a Junky Cerebrum (PML) and BK virus leads to Bad Kidneys (nephropathy in immunocompromised patients).”

Enveloped RNA viruses

Paramyxoviridae

Viral family Capsid Genetic structure Important examples Diseases
Pneumovirus
  • Helical
  • Linear
  • -ssRNA
  • Nonsegmented
  • Fusion protein (F protein) on surface: special virulence factor that causes fusion of respiratory epithelial cells → formation of multinucleated cells
Morbillivirus
Rubulavirus
Paramyxovirus
  • Parainfluenza virus
    • Transmission via airborne droplets
    • Infects upper respiratory tract
    • Young children and infants are commonly affected
    • Relevant in both human and veterinary medicine
  • Upper respiratory infections
  • Lower respiratory infections
  • Croup

PaRaMyxovirus includes Parainfluenza, RSV, and Measles/Mumps/(human) Metapneumovirus.

Flaviviridae

Virus genus Capsid Genetic structure Important examples Diseases
Hepacivirus
  • Icosahedral
Flavivirus (Belong to the arboviruses)
  • Icosahedral
  • Yellow fever virus
    • Reservoir: primary monkeys
    • Vector: mosquito (after inoculation, the virus replicates in dendritic cells)
    • Predominant occurrence in Africa and South America
    • Vaccination of persons at risk of exposure (e.g., travelers)
  • Dengue virus
    • Reservoir: humans
    • Vector: mosquitoes
    • Predominant occurrence in the Caribbean, South America, Southeast Asia, and Oceania
  • West Nile virus
    • Reservoir: wild birds, horses, and dogs
    • Vector: mosquitoes from Aedes, Culex, or Anopheles species
    • Predominant occurrence: Asia, Africa, and the Middle East (endemic)
  • St. Louis encephalitis virus
    • Reservoir: primarily wild birds and domestic fowl
    • Vector: mosquitoes (Culex spp.)
    • Predominant occurrence: regions between Argentina and Canada (primarily in the western, midwestern, and southwestern US)
  • Zika virus
    • Reservoir: primarily African monkeys and other primates
    • During outbreaks, human-to-vector-to-human transmission occurs
    • Vectors: mosquitoes (Aedes aegypti and Aedes albopictus)
    • Predominant occurrence: South America, Africa, and Southeast Asia

ARBOvirus is an acronym for ARthropod BOrne virus.

Orthomyxoviridae

Viral genus Capsid Genetic structure Important examples Diseases
Influenza viruses
  • Helical

Other enveloped RNA viruses

Virus genus Capsid Genetic structure Important examples Diseases
Rhabdoviridae
  • Helical
Coronaviridae
  • Helical
Retroviridae
  • Complex and conical (HIV)
  • Icosahedral (HTLV)
Bunyaviridae: recently reclassified as the order Bunyavirales
  • Helical
  • -ssRNA (3 segments)
  • Pseudocircular
  • Hantavirus
    • Different subtypes depending on geographical region
    • Reservoir: rodents
    • Routes of transmission
      • Aerogens by contaminated dust
      • Bite from an infected animal
  • La Crosse virus
    • Reservoir: chipmunks, foxes, squirrels, and woodchucks
    • Vector: mosquito
Arenaviridae
  • Helical
  • +ssRNA and -ssRNA (2 segments)
  • Circular
  • Lassa virus
    • Occurs mainly in West Africa
    • Reservoir: rats
Togaviridae
  • Icosahedral
  • Western Equine Encephalitis virus
    • Occurs on the west coast of the United States
    • Reservoir: horses, birds
    • Vectors: mosquitoes (Culex tarsalis mosquito and Aedes spp.)
  • Eastern Equine Encephalitis virus
    • Occurs primarily in the east of the Mississippi River (e.g., New York, New Jersey, Michigan)
    • Reservoir: horses, birds
    • Vectors: mosquitoes (Culiseta melanura)
  • Chikungunya virus
    • Mainly occurs in tropical and subtropical regions
    • Reservoir: monkeys
    • Vector: mosquito (Aedes aegypti, Aedes albopuctis)
Filoviridae
  • Helical
Deltaviridae
  • Unknown

To remember that TOGAviridae include CHIKungunya virus, Eastern and Western Equine Encephalitis virus, and RUBella virus, think: “Chico put on his TOGA and searched EAST and WEST for the precious RUBy.”

To remember that HDV can only replicate in the presence of HBV, think: “HDV is Deficient without a Buddy (HBV).”

Nonenveloped RNA viruses

Picornaviridae

Viral family Capsid Genetic structure Important examples Diseases
Enterovirus
  • Icosahedral
Hepatovirus
  • Hepatitis A virus (HAV)
    • High infection rate from infected water and food, particularly in subtropical and tropical regions
    • Transmission: fecal-oral
    • No chronicity
    • Prevention: inactivated vaccine for persons at risk and travelers to endemic regions.

To remember that COxsackie virus, HAV, POLiovirus, RHInovirus, and ECHOvirus are PICornaviridae, think: “The COps HAVe a POLice RHINO that ECHOS any song they PICk.”

Other nonenveloped RNA viruses

Viral genus Capsid Genetic structure Important examples Diseases
Astroviridae
  • Icosahedral
  • Astrovirus
    • Infectious one day before and one day after clinical manifestation of disease
    • Transmission: fecal-oral
Reoviridae
  • Icosahedral (double or triple layer)
  • dsRNA
  • Mulitsegmented (10–12 segments)
  • Linear
Hepeviridae
  • Icosahedral
  • Hepatitis E virus (HEV)
    • Reservoir: wild boars, domestic pigs
    • Transmission: fecal-oral
Caliciviridae
  • Icosahedral
  • Norovirus
    • Only occurs in humans
    • Transmission: fecal-oral and aerosols (e.g., during vomiting)
    • Highly contagious

COLTIvirus causes COLorado TIck fever.