Encyclopedia of Virology, Fourth Edition - Human Immunodeficiency Virus (Retroviridae)

Human immunodeficiency virus type 1 (HIV-1) is a human retrovirus in the lentivirus genus. As a retrovirus it copies its RNA genome into DNA using its own DNA polymerase, reverse transcriptase. Approximately 100 years ago HIV-1 entered the human population via an inter-species transmission event from a chimpanzee to start a worldwide epidemic that has resulted in an estimated 75 million people infected, half of whom have died because of their infection. HIV-1 is an enveloped, plus-stranded RNA virus whose genome encodes 10 genes that give rise to 15 final active proteins. The virus primarily infects CD4+ T cells and to a lesser extent other monocyte-derived cell types. Infection requires the presence of the primary surface receptor, CD4, and one of two secondary surface coreceptors, usually CCR5 or sometimes CXCR4. The virus life cycle begins with entry, followed by synthesis of a linear double-stranded DNA product in the cytoplasm that then migrates to the nucleus where it undergoes integration into the host genome. The integrated viral DNA is expressed as mRNA by the host transcription machinery with viral proteins and full length genomic RNA assembling a virion particle while budding out through the cell plasma membrane. Untreated infection leads to a decline in the target CD4+ T cells which ultimately manifests clinically as immunodeficiency (i.e., AIDS). To prevent the onset of AIDS, HIV-1 is treated with multiple antiretroviral agents, with the drugs typically targeting viral proteins that function at different stages in the virus life cycle. While modern therapy is effective in suppressing viral replication, it is not curative due to the omnipresent latent viral reservoir that leads to the rebound of replicating virus if therapy is discontinued. The course of the HIV-1 epidemic is finally changing through increasing access to treatment and many approaches to prevention. However, eradicating the latent reservoir represents a major challenge that will have to be overcome to effect a true cure for HIV-1.