SnapShot: HIV-1 proteins

Human immunodeficiency virus type-1 (HIV-1) is the etiologic agent of acquired immunodeficiency syndrome ( AIDS) and the prototypic member of the lentivirus genus of retroviruses. Lentivirus infections are considered as chronic or slow and, when pathogenic ( most notably, HIV-1 infection of humans), are associated with severe immunological and neurological dysfunction. HIV-1 has nine genes, with only the gag, pol, and env genes common to all replication-competent retroviruses. The pol gene encodes two enzymes that define the replicative strategy of the retrovirus: reverse transcriptase (RT) copies the viral RNA genome into DNA, and integrase ( IN) mediates the insertion of that DNA into the genomic DNA of an infected cell to establish the provirus ( and persistent infection). A third enzyme protease ( PR), also derived from pol, is necessary for maturation of virions into an infectious form. Of the remaining six regulatory/accessory genes of HIV-1, tat and rev are essential for virus replication, whereas vif, vpr, vpu, and nef are thought to modulate immune functions in vivo ( often in a species-specific fashion). Current frontline highly active antiretroviral therapy ( HAART) for treating AIDS includes combinations of small-molecule inhibitors of PR and RT ( nucleoside RT inhibitors, NRTIs; non-nucleoside RT inhibitors, NNRTIs). A peptide inhibitor of TM that inhibits viral entry is used in salvage therapy, and a small-molecule IN inhibitor, Raltegravir, was recently approved by the FDA. Three crucial viral enzymes are inhibited pharmacologically, but blocking remaining viral proteins and virus-host interactions is an important objective ( a CCR5 coreceptor antagonist, Maraviroc, received FDA approval in 2007).