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Structure and genome of HIV

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The genome and proteins of HIV have been the subject of extensive research since the discovery of the virus in 1983.[1][2] The discovery of the virus itself was not until two years after the first major cases of AIDS associated illnesses were reported in 1981.[3][4]

Structure

File:HIV Viron.png
Figure 1. Diagram of HIV

HIV is different in structure from other retroviruses. It is around 120 nm in diameter (120 billionths of a meter; around 60 times smaller than a red blood cell) and roughly spherical.

HIV-1 is composed of two copies of single-stranded RNA enclosed by a conical capsid comprising the viral protein p24, typical of lentiviruses (Figure 1). The RNA component is 9749 nucleotides long[5]. This is in turn surrounded by a plasma membrane of host-cell origin. The single-strand RNA is tightly bound to the nucleocapsid proteins, p7 and enzymes that are indispensable for the development of the virion, such as reverse transcriptase and integrase. The nucleocapsid (p7 and p6) associates with the genomic RNA (one molecule per hexamer) and protects the RNA from digestion by nucleases. A matrix composed of an association of the viral protein p17 surrounds the capsid, ensuring the integrity of the virion particle. Also enclosed within the virion particle are Vif, Vpr, Nef, p7 and viral protease (Figure 1). The envelope is formed when the capsid buds from the host cell, taking some of the host-cell membrane with it. The envelope includes the glycoproteins gp120 and gp41.

As a result of its role in virus-cell attachment, the structure of the virus envelope spike, consisting of gp120 and gp41, is of particular importance. It is hoped that determining the envelope spike's structure would contribute to scientific understanding of the virus and its replication cycle, and help in the creation of a cure[6]. The first model of its structure was compiled in 2006 using cryo-electron microscopy and suggested that three copies of gp120-gp41 heterodimers are thought to form a trimer as the envelope spike[7]. However, published shortly after was evidence for a single-stalk "mushroom" model, with only the head, consisting of a trimer of three gp120s with a single gp41 glycoprotein, anchoring it to the envelope [8]. There are various possibilities as to the source of this difference, as it is unlikely that the viruses imaged by the two groups were structurally different[9]. More recently, further evidence backing up the heterodimer trimer-based model has been found[10].

Genome organization

File:HIV genome.png
Figure 2. Diagram of the HIV genome

HIV has several major genes coding for structural proteins that are found in all retroviruses, and several nonstructural ("accessory") genes that are unique to HIV. The gag gene provides the basic physical infrastructure of the virus, and pol provides the basic mechanism by which retroviruses reproduce, while the others help HIV to enter the host cell and enhance its reproduction. Though they may be altered by mutation, all of these genes except tev exist in all known variants of HIV; see Genetic variability of HIV.

  • env (for "envelope"): Codes for gp160, the precursor to gp120 and gp41, proteins embedded in the viral envelope which enable the virus to attach to and fuse with target cells.
  • tev: This gene is only present in a few HIV-1 isolates. It is a fusion of parts of the tat, env, and rev genes, and codes for a protein with some of the properties of Tat, but little or none of the properties of Rev.

References

  1. ^ Barré-Sinoussi F, Chermann JC, Rey F; et al. (1983). "Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS)". Science (journal). 220 (4599): 868–71. PMID 6189183. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  2. ^ Gallo RC, Sarin PS, Gelmann EP; et al. (1983). "Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS)". Science (journal). 220 (4599): 865–7. PMID 6601823. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  3. ^ Centers for Disease Control and Prevention (1981-06-05). "Pneumocycstis Pneumonia - Los Angeles" (PDF). Morbidity and Mortality Weekly Report. 30: 250–2. Retrieved 2008-05-10. {{cite journal}}: Cite has empty unknown parameter: |coauthors= (help)
  4. ^ Centers for Disease Control and Prevention (1981-07-04). "Kaposi's Sarcoma and Pneumocycstis Pneumonia Among Homosexual Men - New York City and California" (PDF). Morbidity and Mortality Weekly Report. 30: 305–8. Retrieved 2008-05-10. {{cite journal}}: Cite has empty unknown parameter: |coauthors= (help)
  5. ^ Ratner L, Haseltine W, Patarca R; et al. (1985). "Complete nucleotide sequence of the AIDS virus, HTLV-III". Nature. 313 (6000): 277–84. doi:10.1038/313277a0. PMID 2578615. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  6. ^ "3D structure of HIV is 'revealed'". Health. BBC NEWS. 2006-01-24. Retrieved 2008-08-06. {{cite web}}: Cite has empty unknown parameter: |coauthors= (help)
  7. ^ Zhu P, Liu J, Bess J Jr; et al. (2006). "Distribution and three-dimensional structure of AIDS virus envelope spikes". Nature. 15: 817–8. PMID 16728975. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  8. ^ Zanetti G, Briggs JAG, Grunewald K; et al. (2006). "Cryo-electron tomographic structure of an Immunodeficiency Virus Envelope complex in situ test". PLoS Pathology. 2: e83. doi:10.1371/journal.ppat.0020083. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  9. ^ Sriram Subramaniam (2006). "The SIV Surface Spike Imaged by Electron Tomography: One Leg or Three?". PLoS Pathogens. 2: e91. doi:10.1371/journal.ppat.0020091.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  10. ^ Zhu P, Winkler H, Chertova E; et al. (2008). "Cryoelectron Tomography of HIV-1 Envelope Spikes: Further Evidence for Tripod-Like Legs". PLoS Pathogens. 4: e1000203. doi:10.1371/journal.ppat.1000203. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  • Hunt R. "HIV and AIDS". Human Immunodeficiency Virus and AIDS. University of South Carolina School of Medicine. Retrieved 2008-08-06. {{cite web}}: Cite has empty unknown parameter: |coauthors= (help)
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