Structure of Human Immunodeficiency Virus (HIV)

Human immunodeficiency virus (HIV) is a complex RNA virus of the genus Lentivirus within the Retroviridae family. HIV is an approximately 100 nm icosahedral structure with 72 external spikes that are formed by the two major envelope glycoproteins gp120 and gp41. Two major types of the AIDS virus, HIV- 1 and HIV-2, have been identified. The major serological differences reside in the surface protein gp120. HIV-1 and HIV-2 are further separated into subtypes or ‘clades’ due to the marked variability in the V3 (variable region) of the gp120 protein.

The lipid bilayer is also studded with a number of host-cell proteins during the budding process. HIV has a characteristic dense, cone-shaped nucleocapsid composed of the core protein p24. This nucleocapsid harbours two identical copies of the 9.8 kb single-stranded positive polarity  RNA genome which are associated with the viral enzymes reverse transcriptase (RT), RNase H, integrase, and protease.

HIV encodes 3 structural genes and 6 regulatory genes.
Structural genes:

1. Group-Specific Antigen (Gag): p24, p7, p17)
2. Envelope (Env): gp 120, gp 41
   1. On the basis of gp120 genes, HIV is divided into subtypes (clades): A through I
   2. gp120 binds to CD4 on CD4+ T lymphocytes and cells of the monocyte/macrophage lineage and coreceptors (CCR5 and CXCR4)
   3. gp41 mediate fusion between the cellular and viral membranes.
3. Polymerase (Pol): Reverse transcriptase, integrase, protease

In addition to structural genes HIV has genes whose products contribute to the complex regulation and replication of the virus. Of particular interest is the Nef (negative factor) protein. Deletions and mutations of this protein have been found in some HIV-infected individuals characterized as long-term non-progressors.

Regulatory genes found in HIV

Required for replication

1. Tat: Activation of transcription of viral genes
2. Rev: Transport of late mRNAs from the nucleus to the cytoplasm

Not required for replication

1. Nef: Decreases CD4 and MHC class I protein expression in virus-infected cells (?mutation in the nef gene).
2. Vif: Enhances viral infectivity
3. Vpr: Transports viral core from the cytoplasm into the nucleus
4. Vpu: Enhances virion release from the cell.