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viruses

viruses

features of viruses in general:

  • Viruses differ from rickettsiae in that they all must convert to a non-infective 'eclipse phase' form during replication & that the synthetic processes during replication take place in the host cell cytoplasm & not within the organism itself as in all other classes of organisms.
  • A single virus particle, called a virion, is made up of a core consisting of a single molecule of nucleic acid, & a surrounding protein shell called a capsid.
  • Some viruses are also ensheathed in one or more outer membranes, or envelopes, composed predominantly of lipid, derived in part from the host cell or nuclear membrane prior to the release of the virus. Enveloped viruses are vulnerable to fat solvents such as ether or bile salts.
  • Larger viruses (esp. pox viruses), also contain CHOs, co-enzymes & even some enzymes (eg. lipase, catalase, phosphatase & polymerases) but none contain all enzymes necessary for its own metabolism → all viruses are obligate intracellular parasites.
  • Plant viruses all contain RNA, whereas nearly all bacteriophages contain DNA.
  • Most RNA viruses contain a single strand (except reoviruses) whilst most DNA viruses contain a double strand (except parvoviruses).

Transmissibility:

  • reproduction number = avg. number of secondary cases of disease generated by a typical primary case in a susceptible population
  • reproduction numbers for selected infectious diseases:

Taxonomy:

Viruses may be classified into 20 mammalian families by mode of replication:

DNA viruses:

Class I:
  • Double-stranded DNA → RNA polymerase → mRNA
  • Replicate via DNA polymerase;
  • Use host RNA polymerase (most):
    • a) use host DNA polymerase:
      • adenoviridae
    • b) have own DNA polymerase:
      • herpetoviridae - enveloped, 3 groups of human viruses:
        • neurotropic alpha group:
        • lymphotropic, roseola beta group:
          • CMV, exanthem subitum: human herpesvirus-6 and human herpesvirus-7
          • HHV-5 aka CMV
          • HHV-6B spreads via saliva and infects nearly all children and causes roseola and febrile seizures
          • HHV-6A may account for 40% of unexplained infertility and 10% of all female infertility 1)
        • gamma group:
      • hepadnaviridae
        • hepatitis B virus (partially ds DNA)
          • has reverse transcriptase activity
          • genomic replication via RNA intermed.!
      • papovaviridae (PApilloma, POlyoma, Simian Vacuolating Agent):
        • polyomavirus (non-enveloped) (see web article):
          • BK & JC viruses:
            • transmission via oral/resp. route
            • primary infection usually in childhood & causes mild respiratory illness then remain latent in urogenital tract
            • asymptomatic reactivation & intermittent shedding of virus & uroepithelial cells in urine occurs spontaneously in immunocompetent persons but are more frequent in those with altered cellular immunity (eg. pregnancy, chemotherapy, HIV-1, allograft recipients)
            • BK (disc. 1971 from immunosuppressed kidney transplant pt)
              • worldwide seroprevalence in adults is 60-80%
              • may cause haemorrhagic cystitis or BK viral nephropathy, but overt disease is rare & usually associated with immunocompromise
              • reactivation appears to be cause of severe renal allograft dysfunction
              • found in some human tumours but ? causal
            • JC (disc. 1971 from pt with Progressive Multifocal Leukencephalopathy)
              • causes Progressive Multifocal Leukencephalopathy esp. in immunocompromised pts
          • simian virus 40 (disc. 1961)
  • Have own RNA & DNA polymerase:
    • poxviridae - smallpox, vaccinia - enveloped
Class II: Single-stranded DNA
  • parvoviridae - Norwalk agent

RNA viruses:

  • unique as the only organisms that use RNA instead of DNA.
  • replication is complex & depends on whether contains single- or double- stranded RNA.
  • RNA that acts as mRNA is termed a positive strand.
Double-stranded RNA viruses:
  • Class III:
    • Double-stranded RNA → viral RNA polymerase → mRNA
    • reoviridae - reovirus, rotavirus, orbivirus (Colorado tick fever)
Single-stranded RNA viruses:
  • Class IV:
    • Replication of plus-stranded viruses in which the input strand functions as mRNA:
      • picornaviridae:
        • enterovirus: poliovirus, Coxsackie, ECHO
        • rhinovirus
        • cardiovirus
        • aphthovirus - foot and mouth virus
        • parechovirus - mostly mild rash/diarrhoeal illness but may cause severe neonatal illness involving CNS or causing a sepsis-like illness
        • infectious bronchitis virus; OC43; mouse hepatitis virus;
        • SARS virus;
        • torovirus
      • togaviridae: - enveloped
        • rubivirus: rubella
        • alphavirus: Western equine encephalitis virus; Sindbis virus; Semliki forest virus;
      • flavaviridae:
        • flavivirus (flavus is latin for yellow): 
          • relatively new viruses, derived from a common ancestor 10-20,000yrs ago & are rapidly evolving to fill new ecological niches
          • cause arboviral encephalitis
          • yellow fever virus; dengue virus; Japanese encephalitis; West Nile virus, Kunjin virus & Murray Valley encephalitis virus;
        • hepacivirus:
      • caliciviridae:
      • astroviridae - non-enveloped causes infantile gastro.
        • arteriviruses
        • sequiviridae
        • nodaviridae - mainly non-human
  • Class V:
    • Replication of minus-stranded RNA viruses in which mRNA is complementary to input RNA: (All enveloped)
    • orthomyxoviridae: influenza
    • order Mononegavirales:
  • Class VI:
    • RNA retroviruses → reverse transcriptase → DNA
    • HTLV-1, HIV / AIDS

Typical Viral Genome Parts & Their Protein Products:

  • POL - reverse transcriptase (polymerase)
  • GAG - group antigen protein
  • protease
  • integrase
  • ribonuclease
  • ENV - viral coat protein
  • trans… activation
  • regulatory parts:
    • eg. HIV: act on TAR part LTR
    • NB. NF-KB from cytokines & HTLV-1 tax may also act on TAR → replication HIV;
  • virokines:
    • esp. DNA viruses;
    • act on non-infected cells to modulate progress of infection on body as whole:
    • negate interferons/TNF;
    • decrease inflammatory response;
    • block complement pathway;
    • stimulate metab. activity &/or prolif. nearby cells;
    • decr. MHC I on cell surface (eg. adenovirus, poxvirus);
  • NB. DNA viruses tend to have 10-100's of genes whereas most RNA viruses have < 12, thus for vaccinia (DNA virus) 56 out of 198 Open Reading Frames are not required for replication in cultured cells & presumably they confer survival advantage by sabotaging host immune system;
  • Thus, typical RNA retrovirus genome:
    • 5' - LTR — GAG — POL — ENV — xxx — LTR - 3'
      • where xxx = oncogene, etc;

Laboratory Diagnosis:

  • cell culture (gold standard but ? replaced by PCR?)
  • serology
  • rapid diagnostic techniques:
  • immunoflourescence
  • immunoelectron microscopy
  • radioimmunoassays
  • enzyme immunoassays (ELISA)
  • monoclonal Ab's for detector phase;
  • PCR
    • takes 8hrs to amplify a gene a million times through 25-30 cycles amplification but not quantitative & contamination a major problem;
viruses.txt · Last modified: 2019/06/15 10:24 by wh