Virus

Aka: Virus, Viral Infection, Viral Infectious Disorder, Viral Disease, RNA Virus, DNA Virus, Icosahedral Viral Capsid, Helical Viral Capsid, Enveloped Virus, Positive Sense ssRNA Virus, Negative Sense ssRNA Virus

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II. Pathophysiology

  1. VIruses are microscopic infectious agents, invisible by light microscopy, with 2 components
    1. Nuclear material (either RNA or DNA, but NOT both)
      1. Nucleic Acids may be single stranded (SS) or double stranded (DS)
      2. Nucleic Acids may be looped or linear
      3. Nucelic acids may be segmented into sections or in a single continuous strand
    2. Glycoprotein envelope (nucleocapsid or capsid) surrounds the nuclear material
      1. Enveloped Viruses have an additional lipid bilayer that surrounds the capsid (see below)
  2. Viruses cannot function or reproduce without infecting other organisms
    1. Viral DNA or RNA is expressed by the infected host machinary
    2. Viruses float freely until contacting infectable cells
    3. Unlike Bacteria, viruses contain no organelles or ribosomes
  3. Capsid
    1. Capsomer
      1. Globular Protein collection of one or more polypeptide chains
    2. Capsid Types
      1. Icosahedral Symmetry Capsids (20 sided capsule)
        1. Capsomers (e.g. 20) are organized into an equilateral triangle (e.g. 5x5x5)
        2. Twenty equilateral triangles are combined to form an Icosahedron
        3. Icosahedral capsule contains either DNA or RNA cargo
      2. Helical Symmetry Capsids
        1. Capsomers bind certain RNA Viruses at some nucelotides along the RNA strand
        2. RNA coils into a helix (or into the case of Rhabdoviruses, a bullet shape)
  4. Envelope
    1. Non-Enveloped Viruses (Naked Viruses)
    2. Enveloped Viruses
      1. Some viruses acquire a lipid bilayer outer membrane (surrounding their capsid)
      2. Envelope forms from the host cell's lipid bilayer
        1. Occurs when the virus buds off the surface, on escaping the cell
        2. Envelope includes Glycoproteins embedded in the original host cell bilayer
  5. Replication
    1. Absorption and Host Cell Penetration
      1. Virus binds host cell receptors via capsid Protein or envelope Glycoprotein
      2. Virus is internalized via endocytosis or envelope bilayer fusion with host bilayer
        1. Includes entire virus (capsid and Nucleic Acids)
    2. Viral Uncoating
      1. Nucleic Acids are released into cytoplasm from the viral capsid
    3. Viral Product Synthesis and Assembly
      1. Transcription, translation and replication are specific to DNA and RNA Viruses (see below)
    4. Virion Release from host cells
      1. Enveloped Virions
        1. Virions bud through the host machinary to acquire a bilayer envelope
        2. Bilayer acquired by budding through the hosts golgi, nuclear or cytoplasmic membrane
      2. Non-Enveloped Virions (naked virions)
        1. Released via exocytosis or cell lysis
  6. Host Cell Outcomes
    1. Cell Death (e.g. cell lysis)
      1. Viral replication replaces the host's other cellular functions, and the cell dies
    2. Transformation
      1. Uninhibited cellular (cancer) growth related to Oncogene transmission
    3. Latent Infection
      1. Virus remains inactive in a hibernating state without clinical findings
      2. Reactivation occurs at a later date with various triggers
    4. Chronic slow infection
      1. Slowly progressive effects

III. Type: DNA Viruses

  1. General
    1. All DNA Viruses replicate in the nucleus EXCEPT Poxviridae which replicates in the cytoplasm
    2. DNA Virus replication is more complex than RNA Virus and is divided into stages
      1. Early Transcription
        1. Generation of mRNA encoded Proteins important for DNA Virus replication
      2. Late Transcription
        1. Generation of mRNA encoded Proteins important for the capsid and virion release
  2. Single Stranded (ssDNA)
    1. Parvoviridae (Human Parvovirus B19)
      1. Only ssDNA virus known to be a human pathogen
      2. Icosahedral, non-enveloped (naked) virus
  3. Double Stranded (dsDNA)
    1. Background
      1. dsDNA viruses must be transcribed into mRNA before they can be translated into Protein
      2. dsDNA viruses have 2 strands (one negative, one positive)
        1. Negative strand is transcribed into mRNA
    2. Enveloped (all are icosahedral EXCEPT Poxvirus)
      1. Hepadnavirus (Hepatitis B)
      2. Herpesvirus (Herpes Simplex Virus)
      3. Poxviridae or Poxvirus (e.g. Smallpox, Monkeypox)
        1. Poxviridae are unlike other dsDNA viruses that are more simple, and primarily icosahedral
        2. Poxviridae have complex dsDNA genomes coding for hundreds of Proteins
        3. Poxviridae is encased within a box-like complex of structural Proteins
    3. Non-Enveloped (naked, of which all are icosahedral)
      1. Papovavirus (JC Virus)
      2. Adenovirus (Human Adenovirus)

IV. Type: RNA Viruses

  1. General
    1. All RNA Viruses replicate in the cytoplasm EXCEPT Retrovirus, Orthomyxovirus which replicate in nucleus
  2. Double Stranded
    1. Reovirus or Reoviridae (Rotavirus)
      1. Only dsRNA virus known to be a human pathogen
      2. Icosahedral, non-enveloped (naked) virus
  3. Single Stranded
    1. Message Sense (Positive Stranded, +ssRNA)
      1. Background
        1. Message sense RNA (+ssRNA) are identical to Messenger RNA (mRNA)
        2. Like mRNA, +ssRNA may be immediately translated by host ribosomes into Protein
          1. Exception: Retroviruses are first transcribed into DNA (see below)
      2. Enveloped, Helical Viruses
        1. Coronavirus (Coronavirus)
        2. Retrovirus (Human Immunodeficiency Virus 1)
          1. Background
            1. Retroviruses transcribe DNA from +ssRNA (via their own reverse transcriptase enzyme)
            2. Generated DNA is then incorporated into host DNA
          2. Oncoretroviruses (cancer-causing Retroviruses)
            1. Human T-lymphotropic virus (HTLV) causes Leukemia
          3. Spumaviruses (foamy viruses)
            1. Humans may be infected with simian foamy virus on contact with primates
          4. Lentiviruses (slow viruses)
            1. Human Immunodeficiency Virus 1 (HIV-1)
            2. Human Immunodeficiency Virus 2 (HIV-2)
      3. Enveloped, Icosahedral Viruses
        1. Togavirus (Rubella Virus)
        2. Flaviviridae
          1. Flavivirus (Yellow Fever virus, West Nile Virus, Dengue virus)
          2. Hepacivirus (Hepatitis C Virus)
      4. Non-Enveloped, Icosahedral VIruses (naked viruses)
        1. Picornavirus (Polio Virus, Enterovirus, Hepatitis A Virus)
        2. Calicivirus (Norwalk Virus)
    2. Anti-Message Sense (Negative Stranded, -ssRNA)
      1. Background
        1. Anti-Message sense RNA (-ssRNA) need to first be transcribed into +ssRNA
        2. RNA dependent RNA Polymerase (RNA replicase, RdRp)
          1. RdRp is an enzyme carried by the -ssRNA virus within its capsid
          2. RdRp transcribes -ssRNA into +ssRNA within the host cell
        3. Translation follows +ssRNA transcription from -ssRNA (by RdRp)
          1. As with mRNA, +ssRNA translated by host ribosomes into Protein
      2. Enveloped Viruses (all are helical symmetry. although Rhabdovirus is bullet-shaped)
        1. Filovirus (Marburg Virus)
        2. Paramyxovirus (Measles Virus)
        3. Orthomyxovirus (Influenza Virus)
        4. Bunyavirus (California Encephalitis Virus)
        5. Arenavirus (Lassa Fever)
        6. Rhabdovirus (Rabies Virus)
          1. Helical symmetry, but Bullet-shaped

V. Resources

  1. Gelderblom (1996) Structure and Classification of Viruses, in Baron, Medical Microbiology, 4th ed
    1. https://www.ncbi.nlm.nih.gov/books/NBK8174/

VI. References

  1. Gladwin, Trattler and Mahan (2014) Clinical Microbiology, Medmaster, Fl, p. 226-39
  2. Pellett (2014) Handb Clin Neurol. 2014;123:45-66 +PMID: 25015480 [PubMed]

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