General virology

Basics of virology

A virus is an obligate intracellular parasite, whose metabolic processes, such as protein synthesis, are dependent on the host cell. Viruses do not fulfill all of the criteria for life (e.g., an independent metabolism).

Structure

Viruses do not replicate by division but by assembly of individual components, which are produced in the host cell. They can be differentiated according to their morphology; however, morphological analysis is time-consuming and labor-intensive and is no longer used in the diagnosis of known diseases. The most important viral components include:

  • Genome
  • Capsid: protein coat around the genome
    • Icosahedral or helical structure.
      • Icosahedral
        • Non-enveloped virus with icosahedral capsid
        • Enveloped virus with icosahedral capsid
      • Helical: enveloped virus with helical capsid
  • Envelope
    • Lipid bilayer around the capsid that contains viral glycoproteins and host cell proteins
    • Originates from the host cells but is not present in all viruses
    • Herpesviruses acquire their envelope from nuclear membrane.
    • The presence of the lipid bilayer makes nearly all enveloped viruses vulnerable to rapid inactivation by organic solvents (e.g., alcohol), detergents, and dry heat.
  • Spikes: Viral receptor proteins are required for adhesion to the host cell.
  • Others: Bacteriophages also have a sheath and tail fibers.

Viral life cycle

After infection, viruses reach the corresponding host organism , where they undergo a long replication cycle. The end of this cycle is comprised of individual components.

  1. Attachment (absorption) to the host cell: Viral infection is dependent on characteristics of the host cell surface (e.g., HIV infects all cells with CD4 cell surface receptor molecules).
  2. Penetration into the host cell:
    • Non-enveloped viruses penetrate the host cell by endocytosis or transmembrane transport.
    • Enveloped viruses either fuse with the envelope of the potential host cell or penetrate the cells via endocytosis.
  3. Uncoating of the nucleic acid
    1. Early mRNA is used for protein synthesis.
    2. Late mRNA is used for the synthesis of viral structural proteins.
  4. Replication of the nucleic acid and formation of virus proteins
  5. Assembly of virus components followed by translation and transcription
  6. Viral release: Enveloped viruses are released via budding as opposed to host cell lysis in non-enveloped viruses.

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

Pathogenicity

  • Course: Viral infections can be acute, chronic, latent, or persistent (active ongoing infection)
  • Abortive: No virus production or cell damage.
  • Cytolysis: Destruction of the host cell allows the virus to be released.
    • Seen with naked viruses
    • Some enveloped viruses
  • Immunopathological host reactions: The virus is not cytopathogenic; however, the cellular immune response triggered by cytotoxic T cells leads to the destruction of infected cells (e.g., HBV).
  • Persistent
    • Productive
      • Viruses are produced
      • Senescence (premature cellular aging)
    • Latency
      • No virus produced (during the latent period)
      • Virus remains dormant in infected cells
    • Transforming
      • Viruses can or cannot be produced
      • Immortalization
  • Transfer of genetic material: for example, bacteriophages may transfer virulence factors

Host defense mechanisms and resistance to viral infections

The body has both mechanical (e.g., skin), and immunological mechanisms (e.g., interferon production) to prevent and fight viral infections. Different mechanisms are discussed below.

Mechanism Response
Primary defenses
  • Skin protection
    • Keratinocytes are impermeable to viruses.
    • Normal bacterial skin flora produces acids and inhibitors against viral replication.
    • Mucociliary clearance of the respiratory tract (propels viruses outside the body)
Immune defenses
Interferon

References:[1][2][3][4][5]

Viral genetics

Viral genome replication

  • Viral genomic replication depends on the nucleic acid sequence of the progenitor virus, which include:
Virus type Process of genome replication
dsDNA Without reverse transcriptase (almost all)
  • The negative DNA strand serves as the template for mRNA (made via the host cell RNA polymerase) → new viral proteins and progeny ssRNA are made
With reverse transcriptase (only HBV)
ssDNA Parvoviridae
ssRNA Positive sense Without reverse transcriptase
With reverse transcriptase (HIV, HTLV)
  • Reverse transcriptase transcribes dsDNA from viral ssRNA
  • The negative DNA strand serves as the template for mRNA → new viral proteins and progeny +ssRNA are made
Negative sense
  • Own genome codes for viral polymerase that make mRNA → new viral proteins and progeny -ssRNA are made
dsRNA Reoviridae
  • Not well understood

Viral infectivity

Infectivity of naked viruses based on genetic material

  • Purified nucleic acids of dsDNA viruses and positive ssRNA viruses are infectious.
  • Naked nucleic acids of negative ssRNA viruses and dsRNA viruses are not infectious.
    • 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)
Complementation (viral)
  • Occurs in two different scenarios:
    • Scenario 1: Two mutated viruses from the same or different family infect the same cell.
    • Scenario 2: Mutations in the genome of one virus codes for a nonfunctional protein and a nonmutated virus codes for a functional protein.
      • The functional protein can be used by both mutated and nonmutated virus
        • e.g., HBV codes for HBsAg (an envelope protein), which can be used by Hepatitis D virus. Otherwise, the HDV cannot cause infection.
Phenotypic mixing
  • Occurs with coinfection of a cell with two related viruses (A and B) when the genome of virus A is coated by surface proteins of virus B (forming a pseudovirion).
    • Virus A still determines the genetic material of progeny viruses, including the surface proteins.
    • Surface proteins from virus B determine the tropism.
Phenotypic masking (transcapsidation)
  • Occurs when related viruses infect the same cell.
  • The capsid of one virus envelopes the genome of the other 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 increased viral production, different biological materials should be comparably analyzed.

  • Antibody detection by:
    • Hemagglutination or neutralization test
    • ELISA or immunofluorescence
  • PCR can be usually used for the detection of all viruses. It is used for the quantitative detection of the viral load (e.g., for HIV and HCV); qualitative detection is also possible.
  • Virus isolation is a prerequisite for resistance testing (and is used, e.g., for HIV infection).
  • Time-consuming and labor-intensive methods: not typically used for clinical diagnostics

Enveloped DNA viruses

Viral family Capsid Genetic structure Important examples Diseases
Herpesviridae
  • Icosahedral
  • dsDNA
  • Linear
Hepadnaviridae
  • Icosahedral
  • Partially dsDNA
  • Circular
(Ortho‑)Poxviridae
  • Complex
  • dsDNA
  • Linear

Non-enveloped DNA viruses

Viral family Capsid Genetic structure Important examples Diseases
Adenoviridae
  • Icosahedral
  • dsDNA
  • Linear
  • Adenovirus
    • More than 50 serotypes
    • Transmission by contaminated water or fecal-oral route
    • The different serotypes infect various cells and may persist after primary infection.
Papillomaviridae
  • dsDNA
  • Circular
  • Human papillomavirus (HPV)
    • Comprised of ∼ 100 genotypes
      • Low-risk subtypes: including HPV 6 and 11
      • High-risk subtypes: including HPV 16, 18, 31, and 33 (
    • Transmission especially via sexual intercourse
    • Persistent after primary infection
    • Prevention by active HPV vaccination in teenagers
Polyomaviridae
  • dsDNA
  • Circular
  • JC virus
    • Transmission is likely during childhood.
    • Persistent after primary infection
  • BK virus
    • Airborne transmission during childhood
    • Persistent after primary infection
Parvoviridae
  • ssDNA
  • Linear
  • Parvovirus B19
    • Genetic structure: single-stranded DNA
    • Transmission particularly via airborne infection
    • Demonstrates morphological characteristics
    • Very small virus(< 30 nm)
    • Attaches to P antigen on RBCs
    • Propagates primarily after preferable infection of progenitor cells of erythrocytes, particularly in bone marrow.

Enveloped RNA viruses

Paramyxoviridae family

All are transmitted via airborne droplets.

Viral genus Capsid Genetic structure Important examples Diseases
Pneumovirus
  • Helical
  • Linear
  • Negative-sense ssRNA
  • Respiratory syncytial virus (RSV)
    • Infects ciliated epithelial cells of the respiratory tract
    • Humans are the sole host.
    • Children are particularly affected.
    • Highly contagious
    • Special virulence factors
      • The so-called F protein leads to syncytium formation.
Morbillivirus
Rubulavirus
Paramyxovirus
  • Upper respiratory infections
  • Lower respiratory infections
  • Croup

Flaviviridae family

Viral genus Capsid Genomic structure Important examples Diseases
Hepacivirus
  • Icosahedral
  • Positive-sense ssRNA
  • Linear

Flavivirus (belong to the arboviruses)

  • Yellow fever virus
    • Monkeys are especially a reservoir for dengue virus.
    • Vector: mosquito
      • After a mosquito bite, the virus initially replicates in dendritic cells.
      • Predominant occurrence in Africa and South America
    • Vaccination for persons at risk of exposure is recommended (travelers).
  • Dengue virus
    • Humans are a reservoir.
    • Vector: mosquitoes
      • Predominant occurrence in the Carribean, South America, Southeast Asia, and Oceania
  • West Nile virus
    • Wild birds, horses, and dogs are the primary reservoir.
    • Vector: mosquitoes from the Aedes, Culex, or Anopheles species
      • Predominant occurrence: Asia, Africa, and the Middle East (endemic)
  • West Nile encephalitis
  • St. Louis encephalitis virus
    • Wild birds and domestic fowl are the primary reservoirs.
    • Vector: mosquitoes that belong to the Culex spp
      • Predominant occurrence: regions between Argentina and Canada (primarily in the western, midwestern, and southwestern US)
  • St. Louis encephalitis
  • Zika virus
    • African monkeys and other primates are the primary reservoirs. However, in outbreaks human-to-vector-to-human transmission occurs.
    • Vectors: mosquitoes (Aedes aegypti and Aedes albopictus)
      • Predominant occurrence: South America, Africa, and Southeast Asia

Orthomyxoviridae family

Type Capsid Genetic structure Characteristics Diseases
Influenza viruses
  • Helical
  • Negative-sense ssRNA (8segments)

Further enveloped RNA viruses

Viral family Capsid Genetic structure Important examples Diseases
Rhabdoviridae
  • Helical
  • Negative-sense ssRNA
  • Linear
Coronaviridae
  • Helical
  • Positive-sense ssRNA
  • Linear
  • Coronavirus
    • An important subtype is SARS-CoV.
    • Bats are a likely reservoir.
    • Aerosol transmission
Retroviridae
  • Complex and conical (HIV) or icosahedral (HTLV)
  • Positive-sense ssRNA (2 copies)
  • Linear
  • Express reverse transcriptase
  • HIV
    • Parenteral transmission
    • Important virulence factors
      • Infects cells that carry the CD4 surface antigen
      • Attaches to CCR5 and CXCR4
    • Numerous medical therapies available (see HAART)

Bunyaviridae: recently reclassified as the order Bunyavirales

  • Helical
  • Negative-sense, ssRNA (3 segments)
  • Pseudo-circular
  • Hantavirus
    • Different subtypes depending on the geographical region
    • Reservoirs are rodents.
    • Several routes of transmission
      • Aerogens by contaminated dust
      • Transmission may occur as a result of a bite from an infected animal.
  • Hemorrhagic fever
  • La Crosse Virus
    • Chipmunks, foxes, squirrels, and woodchucks are the primary reservoir
    • Vector: mosquito
  • California encephalitis
Arenaviridae
  • Helical
  • Positive-sense ssRNA and negative-sense ssRNA (2 segments)
  • Circular
  • Lassa virus
    • Occurs mainly in West Africa
    • Reservoir: rats
Togaviridae
  • Icosahedral
  • Positive-sense ssRNA
  • Linear
  • Western Equine Encephalitis virus
    • Occurs in the west coast of the United States
    • Mosquitoes and birds are the primary reservoirs
    • Vector: primarily the 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)
    • Mosquitoes and birds are the primary reservoirs
    • Vector: mosquito Culiseta melanura
  • Eastern equine encephalitis
  • Chikungunya virus
    • Mainly occurs in Sub-Saharan Africa, Southeast Asia, and the Indian subcontinent.
    • The reservoirs are monkeys and the mosquito
    • Vector: mosquito Aedes aegypti (therefore belongs to the arboviruses)
  • Chikungunya fever
Filoviridae
  • Helical
  • Negative-sense ssRNA
  • Linear
  • Ebolavirus/Marburgvirus
    • Occurs in Central and West Africa
    • The natural hosts are most likely fruit bats and monkeys.
  • Hemorrhagic fever

Nonenveloped RNA viruses

Picornaviridae family

Viral genus Capsid Genetic structure Important examples Diseases
Enterovirus
  • Icosahedral
  • Positive-sense ssRNA
  • Linear
  • Echovirus (Enteric Cytopathogenic Orphan Virus)
  • Causes a wide spectrum of diseases
Hepatovirus
  • Hepatitis A virus (HAV)
  • High infection rate from infected water and food particularly in subtropical and tropical regions
  • Transmission: fecal-oral
  • No chronicity!
  • Vaccination with inactivated vaccine for persons at risk and travelers is recommended.
Rhinovirus
  • Rhinovirus
    • More than 110 serotypes
    • Very high incidence
    • Transmission occurs by airborne and smear infections
    • Proliferation is limited to the local portals of entry (nasopharyngeal epithelium)
    • Attaches to ICAM-1 receptors (CD54) on respiratory epithelial cells

Other nonenveloped RNA viruses

Viral family Characteristics Genetic structure Important examples Diseases
Astroviridae
  • Icosahedral
  • Positive-sense ssRNA
  • Linear
  • Astrovirus
    • Infectious one day before and one day after clinical manifestation of disease
    • Transmission: fecal-oral
Reoviridae
  • Icosahedral (double layer)
  • dsRNA (10–12 segments)
  • Linear
  • Rotavirus
    • Special characteristics of the genome
    • Transmission: fecal-oral
    • Vaccination with attenuated virus is recommended for children.
    • In addition to humans, virus reservoirs are also particularly calves and pigs.
Hepeviridae
  • Icosahedral
  • Positive-sense ssRNA
  • Linear
  • Hepatitis E virus (HEV)
  • Wild boars and domestic pigs are likely to be important reservoirs.
  • Transmission: fecal-oral
Caliciviridae
  • Icosahedral
  • Positive-sense ssRNA
  • Linear
  • Norovirus
    • Only occurs in humans
    • Transmission: fecal-oral and aerosols that occur as a result of vomiting
    • Highly contagious
Deltaviridae
  • Still under investigation
  • Negative-sense ssRNA
  • Circular
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last updated 12/14/2018
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