General virology


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 learning card 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 learning cards.

Basics of virology


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.


The most important viral components include:

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
    • Nonenveloped viruses: via endocytosis or transmembrane transport
    • Enveloped viruses: via endocytosis or fusion with host cell's cell membrane
  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

Receptors used by viruses

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


Mechanisms by which viruses cause infection in the host:

  • Cytolysis: viral replication results in the destruction of host cell → release of virus
    • Seen with nonenveloped viruses
    • Some enveloped viruses
  • Immunopathological host reactions: cellular immune response to the invading virus is triggered by cytotoxic T cells destruction of infected cells (e.g., HBV); the virus, however, is not cytopathogenic
  • Transfer of genetic material: bacteriophages may transfer virulence factors (e.g., exotoxins)

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 for details.

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).

Viruses with RNA genomes (RNA viruses)

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

  • Single-stranded RNA (ssRNA)
    • Positive-sense single-stranded RNA (+ssRNA): can be translated directly to form proteins using host ribosome
      • Without reverse transcriptase: viral genome codes for RNA polymerase forms -ssRNA → template for progeny +ssRNA
      • With reverse transcriptase: retroviruses (e.g., HIV, HTLV)
        • Reverse transcriptase transcribes viral ssRNA to dsDNA
        • Negative DNA strand serves as template for mRNA viral proteins and progeny +ssRNA are synthesized
    • Negative-sense single-stranded RNA (-ssRNA): viral genome codes for viral polymerase → mRNA new viral proteins and progeny -ssRNA
  • Double-stranded RNA (dsRNA): Reoviridae

Viral infectivity of nonenveloped viruses

The infectivity of naked viruses is determined by the genome.

  • Purified nucleic acids of dsDNA viruses and +ssRNA viruses are infectious
  • Naked nucleic acids of -ssRNA viruses and dsRNA viruses are not infectious; these require polymerases from complete virion for replication

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)
  • Occurs in viruses with segmented genomes (e.g., influenza, rotavirus)
  • Exchange of genetic material between segments of two viruses from the same strain
  • Causes antigenic shift, which significantly increases the potential of a virus to cause pandemics
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 used by Hepatitis D virus HDV causes infection
Phenotypic mixing (viral)
  • Occurs with coinfection of a cell with two related viruses (virus A and virus B) → genome of virus A is coated by surface proteins of virus B → pseudovirion formation
    • Virus A determines genetic material of progeny viruses (including surface proteins)
    • Surface proteins from virus B determine the tropism
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.



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.

  • Antibody detection
    • Hemagglutination or neutralization test
    • ELISA or direct immunofluorescence (e.g., HSV).
  • PCR: quantitative detection of viral load (e.g., HIV, HCV)
  • Virus isolation: a prerequisite for resistance testing (e.g., HIV)
  • Time-consuming and labor-intensive methods

Enveloped DNA viruses

Viral genus Capsid Genetic structure Important examples Diseases
  • Icosahedral
  • dsDNA
  • Linear
  • Herpes simplex virus-2 (HHV-2)
  • Human herpes viruses 6 and 7 (HHV-6 and 7)
  • Human herpes virus 8 (HHV-8)
  • Icosahedral
  • Partially dsDNA
  • Circular
  • Complex
  • dsDNA
  • Linear

Nonenveloped DNA viruses

Viral genus Capsid Genetic structure Important examples Diseases
  • 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
  • dsDNA
  • Circular
  • Human papillomavirus (HPV)
    • Comprised of ∼ 100 genotypes
      • Low-risk subtypes: include HPV 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 aged 9–45.
  • dsDNA
  • Circular
  • JC virus
    • Transmission usually occurs during childhood
    • Persistent after primary infection
  • BK virus
    • Airborne transmission during childhood
    • Persistent after primary infection
  • ssDNA
  • Linear


Enveloped RNA viruses


Viral genus Capsid Genetic structure Important examples Diseases
  • Helical
  • Linear
  • -ssRNA
  • Respiratory syncytial virus (RSV)
    • Transmission via airborne droplets
    • Highly contagious
    • Infects ciliated epithelial cells of the respiratory tract
    • Most commonly infects children
    • Special virulence factors: F protein syncytium formation
  • Parainfluenza virus
    • Transmission via airborne droplets
    • Infects upper respiratory tract
    • Young children and infants are commonly affected
  • Upper respiratory infections
  • Lower respiratory infections
  • Croup


Virus genus Capsid Genetic structure Important examples Diseases
  • Icosahedral
  • +ssRNA
  • Linear
Flavivirus (Belong to the arboviruses)
  • Icosahedral
  • +ssRNA
  • Linear
  • 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 Carribean, South America, Southeast Asia, and Oceania
  • West Nile virus
    • Reservoir: wild birds, horses, and dogs
    • Vector: mosquitoes
    • Predominant occurrence: Asia, Africa, and the Middle East (endemic)
  • West Nile encephalitis
  • St. Louis encephalitis virus
    • Reservoir: primarily wild birds and domestic fowl
    • Vector: mosquitoes
    • Predominant occurrence: regions between Argentina and Canada (primarily in the western, midwestern, and southwestern US)
  • St. Louis encephalitis
  • Zika virus
    • Reservoir: primarily African monkeys and other primates
    • During outbreaks, human-to-vector-to-human transmission occurs
    • Vectors: mosquitoes
    • Predominant occurrence: South America, Africa, and Southeast Asia


Viral genus Capsid Genetic structure Important examples Diseases
Influenza viruses
  • Helical
  • -ssRNA (8 segments)

Other enveloped RNA viruses

Virus genus Capsid Genetic structure Important examples Diseases
  • Helical
  • -ssRNA
  • Linear
  • Helical
  • +ssRNA
  • Linear
  • Complex and conical (HIV)
  • Icosahedral (HTLV)
  • +ssRNA (2 copies)
  • Linear
  • Express reverse transcriptase
  • HIV
    • Parenteral transmission
    • Important virulence factors
      • Infects cells that carry CD4 surface antigen
      • Attaches to CCR5 and CXCR4
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
  • Hemorrhagic fever
  • La Crosse virus
    • Reservoir: chipmunks, foxes, squirrels, and woodchucks
    • Vector: mosquito
  • California encephalitis
  • Helical
  • +ssRNA and -ssRNA (2 segments)
  • Circular
  • Lassa virus
    • Occurs mainly in West Africa
    • Reservoir: rats
  • Icosahedral
  • +ssRNA
  • Linear
  • 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
  • Eastern equine encephalitis
  • Chikungunya virus
    • Mainly occurs in Sub-Saharan Africa, Southeast Asia, and the Indian subcontinent
    • Reservoir: monkeys
    • Vector: mosquito (Aedes aegypti)
  • Chikungunya fever
  • Helical
  • -ssRNA
  • Linear
  • Hemorrhagic fever
  • Unknown
  • -ssRNA
  • Circular


Nonenveloped RNA viruses


Viral genus Capsid Genetic structure Important examples Diseases
  • Icosahedral
  • +ssRNA
  • Linear
  • 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.

Other nonenveloped RNA viruses

Viral genus Capsid Genetic structure Important examples Diseases
  • Icosahedral
  • +ssRNA
  • Linear
  • Astrovirus
    • Infectious one day before and one day after clinical manifestation of disease
    • Transmission: fecal-oral
  • Icosahedral (double layer)
  • dsRNA (10–12 segments)
  • Linear
  • Icosahedral
  • +ssRNA
  • Linear
  • Icosahedral
  • +ssRNA
  • Linear
  • Norovirus
    • Only occurs in humans
    • Transmission: fecal-oral and aerosols (e.g., during vomiting)
    • Highly contagious
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last updated 08/11/2019
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