Virus

• Overview of virus

  .Small: 20 – 400 nm diameter

  Non-cellular: Genetic element that cannot replicate independently of a living (host) cell 

  Structure:

  •Icosahedral: 20 faces, each an equilateral triangle (eg polio, rhino, adeno)

  •Helical: protein binds around DNA/RNA in a helical fashion

  •Complex: neither icosahedral or helical

  Obligate intracellular pathogens (can only replicate inside host cell)

  Most viruses have a specific host range and only infect specific host cell types (tissue tropism)
• What is a virus, what is a virion, and what are the key characteristics of virology?


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  • A virus is a genetic element that cannot replicate independently of a living (host) cell.
  • Virology is the study of viruses.
  • A virion is the extracellular form of a virus, which exists outside a host cell and facilitates transmission from one host to another. It contains a nucleic acid genome (DNA or RNA) surrounded by a protein coat and sometimes additional layers of material.
• Virions can be classified based on their structure into three main groups: icosahedral, helical, and complex
• Virus families can be classified according to:


  .Virion shape / symmetry

  Presence / absence of envelope

  Genome structure

  Mode of replication 
• Virion Structure

  .Examples of enveloped viruses are flu, HIV and Hep C

  
• Transmission


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• How do viruses infect hosts, and what can happen when human and animal or bird strains co-infect the same organism?


  .Some viruses may only infect humans (e.g., smallpox, measles), while others can infect both humans and other animals or birds. When a novel virus is transmitted to humans, co-infection of human and animal or bird strains in one organism may lead to recombination, potentially generating a new viral strain.

  
• Syndromes


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• Consequences of viral infection


  . Clearance of virus (with no, short or long term immunity)

  •Measles (long term immunity)

   Chronic infection

  •HIV, hepatitis B, hepatitis C

   Latent infection: Herpes Virus

   Transformation (long term infection with altered cellular gene expression)

  •Epstein-Barr Virus, Human Papillomavirus
• Penetration involves the entry of the virus into the cell through various mechanisms such as endocytosis, direct fusion with the plasma membrane, or injection of the viral genome directly into the cytoplasm
• The basic steps involved in the life cycle of a virus include attachment, penetration, uncoating, synthesis of new genomes and proteins, assembly, maturation, release, and infection of other cells
• Viral Latency


  . Following primary infection, some viruses lie dormant in the cell.

  The full viral genome is retained in the host cell, but its expression is restricted, such that few viral antigen and no viral particles are produced.

  Reactivation of viral replication can occur

  Reactivations may or may not cause apparent disease

  Reactivation more likely to occur and more severe in immunocompromised

  Examples: 

  Herpes Simplex Virus

  Varicella Zoster Virus
• Viruses & Cancer


  .A number of viral infections can lead to cancer (often requires some other event to also occur)

  Mechanisms

  Modulation of cell cycle control (driving cell proliferation/growth)

  Modulation of apoptosis (prevention of programmed cell death)

  Reactive oxygen species mediated damage (some persistent viral infections can cause persistent inflammatory processes which lead to cancer via reactive oxygen species)
• Viruses & Cancer


  .Examples

  EBV: Burkitt’s lymphoma, Hodgkin’s lymphoma, nasopharyngeal carcinoma, post-transplant lymphoproliferative disease (PTLD)

  Human herpes virus 8: Kaposi’s sarcoma, primary effusion lymphoma, Castleman’s disease

  Human T-cell Lymphotropic Virus (HTLV): Adult T-cell leukaemia/lymphoma

  Human Papillomavirus (HPV): cervical, anal, oropharyngeal cancers

  Hepatitis B and Hepatitis C: hepatocellular carcinoma
• Detection Methods


  .•Whole organism

  •Part of organism – e.g. antigen, nucleic acid

  •Immune response to a pathogen – i.e. antibodies
• Detection Methods: Whole organism


  -Microscopy

  -Culture

  
• Detection Methods: Part of organism

  -Antigen detection

  -DNA/RNA detection

  Extraction of genetic material from sample

  Amplification of region of target organism genome (if organism present in sample)
• Detection Methods: Immune Response


  .•Similar methods as those used for antigen detection

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  •May be used to determine:

  •Acute / recent infection

  •Prior infection / response to vaccination
• Antiviral Therapy


  . All antiviral agents are virustatic, none are virucidal (

  • Virustatic: Inhibits viral replication without killing the virus.
  • Virucidal: Kills the virus.)

  As viruses utilise host cell enzymes in order to replicate, there are limited viral proteins that are potential targets for antiviral drugs

   Toxicity to the host cell is not uncommon: side effects

   Only used in a minority of viral infections 
• Antivirals may be used for:

  .Prophylaxis (to prevent infection)

  Pre-emptive therapy (when evidence of infection/replication detected, but before symptoms are apparent) 

  Overt disease (a disease that is open to view or readily perceived)

  Suppressive therapy (to keep viral replication below the rate that causes tissue damage in an asymptomatic infected patient)
• Prevention of Viral Infection


  . Immunisation

  •Vaccination

  •Passive immunisation with immunoglobulin

   Prophylactic treatment post exposure

   Infection prevention and control measures

  •Isolation of symptomatic patients

  •Personal protective equipment

  •Safe use and disposal of sharps

   Blood / tissue / organ screening 

  Antenatal screening
• Viruses with the following properties can potentially be eradicated:


  .•No animal reservoir or ability to amplify in the environment

  •Clearly identifiable, with accurate diagnostic tool

  •No chronic carrier state

  •Efficient and practical intervention, e.g. vaccination

  •Political / social support

  Examples:

  Smallpox (eradicated in 1979)

  •Measles    

  •Polio
• Virus replication


  .Virion required for transmission form one host cell to another – (basically wrapping it in a protein coating: a capsid) The capsid is the infective form. You can also sometimes get a lipid coating derived from the host cell.