Diverse world of viruses

• Studies using models to predict future temperature suitability for mosquito vectors have highlighted that certain months of the year will be conducive for Aedes mosquitoes (vectors for Zika and dengue fevers) to breed in temperature regions such as the UK that are currently free from such vectors.
• Up to 90% of UK population is seropositive for HSV.
• Herpes simplex keratitis (HSK) is responsible for 1 in 10 corneal transplants.
• In immunocompromised individuals, such as those with advanced HIV infection, HSV-1 can have more severe symptoms and more frequent recurrences. Rarely, HSV-1 infection can also lead to more severe complications such as encephalitis or keratitis.
• The human papilloma virus (HPV) is a ubiquitous DNA virus that is capable of infecting the human keratinocytes on the skin and mucus membranes.
• Plantar warts are caused by other types of HSV different from that infects the genitalia.
• Genital warts are benign growths occurring in the skin and mucus membranes of the genital areas and anus due to infection with the human papillomavirus.
• Verrucous carcinoma of genitalia (giant condyloma of Bushchke-Lowenstein) is a low-grade, locally invasive, squamous cell carcinoma that is associated with HPV types 6 and 11
• Viral structure

  A) nucleic acid

  B) capsid

  C) lipid envelope

  D) enzymes

  E) viral proteins

  F) nucleocapsid

  
• There are two major structures of viruses called the naked nucleocapsid virus and the enveloped virus.
• • HIV fuses with surface of host cell
  • capsid containing virus genome and proteins enters cell
  • shell disintegrates and reverse transcriptase transcribes viral RNA
  • viral DNA transported across nucleus, HIV integrase integrates HIV DNA into host's DNA
  • host's normal transcription machinery transcribes HIV DNA into multiple copies HIV RNA
  • some becomes genome of new virus, cell uses other copies to make new HIV proteins
  • move to surface of cell, where new immature HIV forms
  • virus released from cell and HIV protease cleaves newly synthesised polyproteins to create mature infectious virus
• The first step of viral replication involves attachment of the virus particle to the cell surface. Depending on the virus, the viral proteins responsible for binding form either projections (glycoprotein spikes, fibres) or depressions in the virus surface
• • fusion of HIV to host cell surface
  • HIV RNA, reverse transcriptase, integrase and other viral proteins enter host cell
  • viral DNA formed by reverse transcription
  • viral DNA is transported across nucleus and integrates into host DNA
  • new viral DNA is used as genomic RNA and to make viral proteins
  • new viral RNA and proteins move to cell surface and a new immature HIV forms
  • virus released. Viral protease cleaves new polyproteins to create mature infectious virus
• Viruses can penetrate the host cell by either fusing with the host cell membrane or by priming the host signalling pathway leading to endocytosis
• HIV and HSV enter host cells by fusion with host cell membrane
• Viruses that enter host cells by macropinocytosis

  • dengue fever
  • ebolavirus
  • herpes simplex virus
  • humman immunodeficiency virus
  • vaccinia virus
• Viruses that enter host cells by clathrin mediated signalling pathway

  • borna disease virus
  • dengue virus
  • human adenovirus
  • hepatitis C virus
  • influenza virus
• Simian virus 40 enters host cells by caveolae and lipid raft pathways.
• The shell of the capsid disintegrates and HIV reverse transcriptase transcribes viral DNA into RNA. Viral DNA is transported across nucleus, where HIV integrase integrates HIV DNA into host's DNA. The host's normal transcription machinery transcribes HIV DNA into multiple copies of new HIV RNA.
• Some of the replicated RNA becomes the genome of new viruses, while cell uses other copies of RNA to make new HIV proteins. The new viral RNA and HIV proteins move to the surface of the cell, where a new immature HIV forms. Finally, the virus is released from the cell, and HIV protease cleaves newly synthesised polyproteins to create a mature infectious virus.
• The current classification of viruses is the International Committee on the Taxonomy of Viruses nomenclature. It is still based on classical Linnaean hierarchical system but primarily depends on the genome and nucleic acid material of the viruses.
• Baltimore classification system - the most commonly used system of virus classification was developed by Nobel Prize winning biologist David Baltimore in the early 1970s. The Baltimore classification scheme groups viruses according to how the mRNA is produced during the replicative cycle of the virus.
• RNA is more stable than DNA due to its chemical structure.
• Baltimore Class I viruses

  • dsDNA
  • HPV, poxvirus, herpes
  • transcription by RNA polymerase
• Baltimore Class II viruses

  • ssDNA
  • adeno-associated virus
  • DNA replication by DNA polymerase then transcription by RNA polymerase
• Baltimore Class III viruses

  • dsRNA
  • reoviruses
• Baltimore Class IV viruses

  • ssRNA (+)
  • SARS, Hep A, Hep C
  • RNA replication by RNA dependent RNA polymerase
• Baltimore Class V viruses

  • ssRNA (-)
  • influenza, ebola
  • RNA replication by RNA dependent polymerase
• Baltimore Class VI viruses

  • ssRNA (+) diploid
  • HIV
  • reverse transcription by reverse transcriptase, DNA replication by DNA polymerase and transcription by RNA polymerase
• Baltimore Class VII viruses

  • gapped dsDNA
  • Hep B
  • DNA repair by DNA polymerase, and reverse transcription by reverse transcriptase
• Flu viruses have the capacity to change both slowly, through small genetic changes that are passed down to daughter generations, and quickly, through a process called reassortment that mixes larger genetic segments from several viral strains to create a new virus. Both processes are important to influenza's success as a disease-causing organism during flu seasons and in pandemics.
• Antigenic drift

  • accumulation of small genomic mutations leading to small change in encoded protein structure
  • two possible outcomes
  • infection cleared. no disease
  • absence of proper immunity leading to disease
• Antiviral drugs can target

  • viral release
  • nucleic acid synthesis
  • viral uncoating
• Saquinavir targets viral release and is indicated for HIV infection, in combination with other retroviral drugs.
• Aciclovir targets nucleic acid synthesis and is indicated for

  • systemic and topical treatment of herpes simplex e.g. herpes encephalitis
  • systemic treatment of varicella zoster
  • prevention of recurrence and prophylaxis in the immunocompromised
  • effective only if started at onset of episode
  • does not eradicate the virus
• Amantadine targets viral uncoating and is licensed for prophylaxis and treatment of influenza A but no longer recommended for postexposure prophylaxis. seasonal prophylaxis or treatment