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 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.

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.

Viral structure

The most important viral components include:

Viral genome

• DNA viruses
  • Double-stranded DNA genomes (dsDNA): most DNA viruses
  • Single-stranded DNA genomes (ssDNA): e.g., Parvoviridae
  • Linear: most DNA viruses
  • Circular: e.g., Papillomaviridae, Polyomaviridae (supercoiled), Hepadnaviridae (incomplete)
• RNA viruses
  • Double-stranded RNA genomes (dsRNA): Reoviridae
  • Single-stranded RNA genomes (ssRNA): most RNA viruses
    • Positive-sense RNA viruses (+ssRNA): e.g., Retroviridae, Togaviridae, Flaviviridae, Coronaviridae, Hepeviridae, Caliciviridae, Picornaviridae
    • Negative-sense RNA viruses (-ssRNA): e.g., Arenaviridae, Bunyaviridae, Paramyxoviridae, Orthomyxoviridae, Filoviridae, Rhabdoviridae
    • Linear: most RNA viruses
    • Circular: e.g., Arenaviridae, Deltaviridae
    • Segmented RNA viruses: A segmented genome facilitates the exchange of genome segments between different virus strains during coinfection of a single host cell (i.e., viral reassortment).
      • Bunyavirus: 3 segments
      • Orthomyxovirus: 8 segments
      • Arenavirus: 2 segments
      • Reovirus: 10–12 segments

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

“A vegan INFLUENCER ate (8) 3 BUNnies and upset 10–12 REaders in 2 AREas: ”INFLUENZA virus has 8 segments, BUNyavirus has 3, REoviruses has 10–12, and AREnaviruses has 2.

Capsid

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

• Helical capsid structure in enveloped viruses
• Icosahedral capsid structure in nonenveloped viruses and enveloped viruses (all DNA viruses are icosahedral except poxvirus, which has a complex capsid)

Envelope

• Lipid bilayer around the capsid that contains viral glycoproteins and host cell proteins
  • 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
  • Usually originates from host cell's plasma membrane when the virion exits the host cell (except Herpesviridae, which acquire their primary envelope from host cell nuclear membranes).
• Some viruses do not possess envelopes. These are referred to as nonenveloped viruses (naked viruses)
  • DNA viruses, e.g., Papillomaviridae, Adenoviridae, Parvoviridae, Polyomaviridae
  • RNA viruses, e.g., Caliciviridae, Picornaviridae, Reoviridae, Hepeviridae

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
   • 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)
   • Early mRNA is for the synthesis of
     • Proteins to shut down host cell defense mechanisms
     • Proteins for genome replication (e.g., viral RNA polymerase)
   • Late mRNA is for the synthesis of viral structural proteins
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:

• 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 viral infection (virus is inactive; no replication): virus remains dormant in infected cells
  • Productive viral infection (viral replication occurs, dormant infection with few or no signs of infection)
  • Transforming viral infection (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.”

• Innate immune response
  • Physical, biological, and chemical defenses
    • Keratinocytes are impermeable to viruses
    • Mucociliary clearance of respiratory tract (transports viruses towards the throat)
    • Production of acid and viral replication inhibitors by commensal organisms
  • RNA interference (only against RNA viruses)
  • Natural killer cells
  • Complement system
  • Interferon: IFN-alpha and IFN-beta
    • Produced by infected cells
    • Triggers damage and death of infected cells
    • Inhibit viral replication and viral protein synthesis
      • RNA endonucleases: cleave phosphodiester bonds between nucleotides
      • Phosphorylation of protein kinases → inactivation of eIF2 → inhibition of protein synthesis
• Adaptive immune response
  • Immunoglobulins
  • T cells

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

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).

• Double-stranded DNA (dsDNA)
  • Without reverse transcriptase (almost all viruses): viral negative DNA strand is transcribed to mRNA using host cell's RNA polymerase → viral proteins and progeny dsDNA are formed
  • With reverse transcriptase: hepadnavirus (only HBV, which is a reverse transcribing virus)
    • Transcription of progeny DNA requires an RNA-dependent DNA polymerase (acts as a reverse transcriptase)
    • Viral DNA is transcribed via host cell RNA polymerase to viral mRNA → viral protein synthesis → HBV RNA-dependent DNA polymerase then reverse transcribes viral RNA to form progeny DNA
• Single-stranded DNA (ssDNA): only Parvoviridae
  • Host cell DNA polymerase converts ssDNA viral genome to dsDNA → negative DNA strand serves as template for mRNA (using host cell's RNA polymerase) → viral proteins and progeny ssDNA are formed

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).

• 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)
    • A negative strand must be transcribed into positive strand first
    • Viral genome codes for viral polymerase → mRNA → new viral proteins and progeny -ssRNA
    • Includes orthomyxovirus, paramyxovirus, arenavirus, filovirus, bunyavirus, and rhabdovirus
• Double-stranded RNA (dsRNA): Reoviridae

To remember that 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.

• Purified nucleic acids of dsDNA viruses and +ssRNA viruses are infectious
  • +ssRNA viruses: equivalent to eukaryotic mRNA → host cell translation machinery produces viral proteins → construction of virions
  • dsDNA viruses: viral DNA transcribed to mRNA → viral protein production by host cell → perpetuation of viral life cycle without intact virions
  • Exceptions: HBV, poxvirus
• -ssRNA and dsRNA viruses are not infectious without the polymerases required for replication.

Genetic diversification

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
  • Viral hemagglutination inhibition test: used in the diagnosis of viral infections (e.g., influenza, mumps, and measles)
    • Patient serum is added to infected cells.
    • If antibodies are present in the serum:
      • A progression of infection in cell culture is inhibited (neutralization of viruses).
      • Hemagglutination will not be observed.
  • 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
  • Cell culture
  • Electron microscopy
  • Not typically used for clinical diagnostics

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).”

Pneumoviridae

Pneumoviruses, e.g., RSV and human metapneumovirus, are no longer members of the Paramyxoviridae family. ^[3]

Paramyxoviridae

ParaMyxovirus includes Parainfluenza and Measles/Mumps/(human).

Flaviviridae

ARBOvirus is an acronym for ARthropod BOrne virus.

Orthomyxoviridae

Other enveloped RNA viruses

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

Picornaviridae

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

COLTIvirus causes COLorado TIck fever.