Human immunodeficiency virus (HIV), the causative agent of AIDS, is a highly mutable lentivirus, a member of the retrovirus family Retroviriadae, whose genome is encoded in RNA. Its shape is spherical, with a 110nm diameter, and it is formed by a lipidic envelope (with p17 protein and gp41 and surface gp120 glycoproteins) and a core (made of p24 proteins), containing two RNA strands (associated to p7 core proteins) and three enzymes: a protease (p11; PR), a reverse transcriptase (p66; RT) and an integrase (p32; IN).
HIV has the gag/pol/env gene organization typical of other retroviruses. Moreover, it has other six expression and maturation genes, and the function of one of these genes is still unknown. The preferred target of the virus is the T4 lymphocyte, whose decrease in number causes heavy damages to the immune system of the infected organism. HIV recognizes a particular surface protein present on the host human cells, the CD4 protein. Once inside the cell, the virus releases its RNA.
Reverse transcriptase (RT), an enzyme unique to retroviruses, transcribes retroviral RNA into DNA, which is then integrated into the host genome by the viral integrase (IN) and expressed by the infected host cell under the control of viral genes.
Much of the genetic information of HIV is carried in the gag, pol, and env genes. In the mid-1980s it was suggested that the pol gene might encode a protease similar to those of other retroviruses. The HIV-encoded structural proteins and enzymes are initially translated as large polyproteins which must be further proteolytically processed in order to produce mature viral particles. The gag gene is translated as a 55 kDa precursor protein which is processed at a late stage in viral replication to give the structural proteins of the viral core. The pol gene is translated only as a 160 kDa gag-pol fusion protein which results from a frame-shift between the overlapping gag and pol open reading frames.
Proteolytic processing of the gag-pol protein produces the viral enzymes as well as structural proteins. The env gene is translated as a 160 kDa protein which is then cleaved to give the viral envelope glycoproteins. Processing of the env protein is carried out by a host cell enzyme, whereas the gag and gag-pol proteins are processed only by the viral aspartic protease (HIV-PR).