The evolution of HIV-1 and the origin of AIDS

Abstract

The major cause of acquired immune deficiency syndrome (AIDS) is human immunodeficiency virus type 1 (HIV-1). We have been using evolutionary comparisons to trace (i) the origin(s) of HIV-1 and (ii) the origin(s) of AIDS. The closest relatives of HIV-1 are simian immunodeficiency viruses (SIVs) infecting wild-living chimpanzees (Pan troglodytes troglodytes) and gorillas (Gorilla gorilla gorilla) in west central Africa. Phylogenetic analyses have revealed the origins of HIV-1: chimpanzees were the original hosts of this clade of viruses; four lineages of HIV-1 have arisen by independent cross-species transmissions to humans and one or two of those transmissions may have been via gorillas. However, SIVs are primarily monkey viruses: more than 40 species of African monkeys are infected with their own, species-specific, SIV and in at least some host species, the infection seems non-pathogenic. Chimpanzees acquired from monkeys two distinct forms of SIVs that recombined to produce a virus with a unique genome structure. We have found that SIV infection causes CD4(+) T-cell depletion and increases mortality in wild chimpanzees, and so the origin of AIDS is more ancient than the origin of HIV-1. Tracing the genetic changes that occurred as monkey viruses adapted to infect first chimpanzees and then humans may provide insights into the causes of the pathogenicity of these viruses.

Figure 1.

Map of west and central Africa, showing the ranges of chimpanzee subspecies (colour coded). The ranges of western lowland gorillas (G. gorilla) and eastern Grauer's gorillas (G. beringei) are superimposed. The gold circle denotes the region in southeast Cameroon where SIVcpz strains closely related to HIV-1 group M are found.

Figure 2.

Origins of HIV-1. The phylogenetic relationships among strains of SIVcpz (black from P. t. troglodytes, grey from P. t. schweinfurthii), SIVgor (blue) and HIV-1 (red). The red crosses mark four branches on which cross-species jumps to humans occurred; the two blue crosses indicate alternative possible branches on which a chimpanzee-to-gorilla transmission occurred. The HIV-1 strains fall into three groups (M, N and O; only two representatives of each group are shown), and a recently described fourth lineage (RBF168). Adapted from trees shown in Takehisa et al. (2009) and Plantier et al. (2009).

Figure 3.

Mosaic structure of the SIVcpz genome. Boxes denote the long terminal repeat (LTR) regions and nine genes (tat and rev each have two exons). The SIVcpz genome arose through recombination; regions in light and dark grey were derived from the SIVrcm and SIVgsn/SIVmus/SIVmon lineages, respectively (the origin of the 5′ exons of tat and rev is difficult to determine).