The scale bar represents 0.10 amino acid replacements per site.Lentiviruses cause chronic persistent infections in various mammalian species, including bovines, horses, sheep, felines, and primates.
The great majority of lentiviruses are exogenous, meaning that they are transmitted horizontally between individuals. These “viral fossils” are of particular interest because they provide direct evidence of the timescale of lentivirus evolution.
However, it has recently become clear that, on several occasions in the past, lentiviruses have infiltrated their hosts’ germlines and become endogenous, vertically transmissible, genomic loci (Fig. Examples include the rabbit endogenous lentivirus type K (RELIK), which became germ-line embedded approximately 12 million years ago (Katzourakis et al. 2009), and two prosimian endogenous lentiviruses, which independently invaded the germ-lines of both the grey mouse lemur (p SIVgml) and the fat-tailed dwarf lemur (p SIVfdl) about 4 million years ago (Gifford et al. Molecular clocks derived from extant SIV sequences suggested that ancestral SIVs existed only a few hundreds of years ago (Wertheim and Worobey 2009), but it has long been suspected that such analyses may grossly underestimate deeper evolutionary timescales (Sharp et al. Recent studies of SIV-infected monkeys on Bioko Island, Equatorial Guinea, partly substantiated this conclusion, showing that geographically isolated subspecies have been infected with the same type of SIV for at least 30,000 years and probably much longer (Worobey et al. The endogenous viruses in lemurs reveal that the span of evolutionary history of primate lentiviruses as a whole is at least two orders of magnitude greater still.
Thus, it is possible that at least some SIVs, such as those infecting four closely related species of African green monkeys ( species), have coevolved with their respective hosts for an extended period of time, perhaps even before these hosts diverged from their common ancestor (Jin et al. So far, SIV infections have only been found in African monkeys and apes, and so it seems likely that primate lentiviruses emerged in Africa sometime after the splits between lineages of African and Asian Old World monkeys, which are believed to have occurred around 6–10 million years ago (Fabre et al. However, because neither Asian nor New World primates have been sampled exhaustively, the conclusion that SIVs are restricted to African primates must remain tentative, especially because none of these primate species has been examined for endogenous forms of SIV (Ylinen et al. Thus, our understanding of the evolutionary history of primate lentiviruses is still incomplete.
To date, serological evidence of SIV infection has been reported for over 40 primate species, and molecular data have been obtained for most of these (also see Klatt et al. The latter studies have shown that the great majority of primate species harbor a single “type” or “strain” of SIV.
Acquired Immune Deficiency Syndrome (AIDS) was first recognized as a new disease in 1981 when increasing numbers of young homosexual men succumbed to unusual opportunistic infections and rare malignancies (CDC 1981; Greene 2007). 2011); however, 80% of adults acquire HIV-1 following exposure at mucosal surfaces, and AIDS is thus primarily a sexually transmitted disease (Hladik and Mc Elrath 2008; Cohen et al. Since its first identification almost three decades ago, the pandemic form of HIV-1, also called the main (M) group, has infected at least 60 million people and caused more than 25 million deaths (Merson et al. Developing countries have experienced the greatest HIV/AIDS morbidity and mortality, with the highest prevalence rates recorded in young adults in sub-Saharan Africa (
A retrovirus, now termed human immunodeficiency virus type 1 (HIV-1), was subsequently identified as the causative agent of what has since become one of the most devastating infectious diseases to have emerged in recent history (Barre-Sinoussi et al. Although antiretroviral treatment has reduced the toll of AIDS- related deaths, access to therapy is not universal, and the prospects of curative treatments and an effective vaccine are uncertain (Barouch 2008; Richman et al. Thus, AIDS will continue to pose a significant public health threat for decades to come. These relationships provided the first evidence that AIDS had emerged in both humans and macaques as a consequence of cross-species infections with lentiviruses from different primate species (Sharp et al. Indeed, subsequent studies confirmed that SIVmac was not a natural pathogen of macaques (which are Asian primates), but had been generated inadvertently in US primate centers by inoculating various species of macaques with blood and/or tissues from naturally infected sooty mangabeys (Apetrei et al. Similarly, it became clear that HIV-1 and HIV-2 were the result of zoonotic transfers of viruses infecting primates in Africa (Hahn et al. In this article, we summarize what is known about the simian precursors of HIV-1 and HIV-2, and retrace the steps that led to the AIDS pandemic. Old World monkeys are naturally infected with more than 40 different lentiviruses, termed simian immunodeficiency viruses (SIVs) with a suffix to denote their primate species of origin (e.g., SIVsmm from sooty mangabeys).
Common chimpanzees have traditionally been further subdivided into a number of geographically differentiated subspecies (Groves 2001). First, only two of the four chimpanzee subspecies were found to harbor these viruses. The absence of SIVcpz from two of the four subspecies suggested that chimpanzees had acquired this virus more recently, after their divergence into different subspecies.
Four subspecies were defined on the basis of mitochondrial DNA sequences (Gagneux et al. To determine the distribution of SIVcpz among these populations, fecal (and in some cases urine) samples were collected at different field sites and tested for the presence of virus specific antibodies. SIVcpz was detected at multiple sites throughout the ranges of both central and eastern chimpanzees in an area ranging from Cameroon to Tanzania, but there was no evidence of infection in western and Nigeria-Cameroonian chimpanzees, nor in bonobos, despite testing of multiple communities. Indeed, phylogenetic analyses of full-length proviral sequences revealed that SIVcpz represents a complex mosaic, generated by recombination of two lineages of SIVs that infect monkeys (Bailes et al. In the 5′ half of the genome, as well as the ) monkeys (Bailes et al. Chimpanzees are known to hunt and kill other mammals, including monkeys (Goodall 1986), suggesting that they acquired SIV in the context of predation.
Examples range from incidental “dead-end” infections (e.g., SIVver infections of baboons) (Jin et al. 1998) to the generation of new SIV lineages with substantial secondary spread (e.g., SIVgor infection of gorillas) (Van Heuverswyn et al. In addition, cross-species transmissions have generated mosaic SIV lineages through superinfection and recombination in species that already harbored an SIV (e.g., SIVsab infection of sabaeus monkeys) (Jin et al. In both mandrills (), such recombination events have led to the emergence of a second SIV strain that cocirculates with the original virus (Souquiere et al. What remains unknown is when and how often these cross-species transfers have occurred, what impact they had on virus and host biology, and whether AIDS is a frequent consequence of SIV host switching.
The prevalence of naturally occurring SIV infections varies widely, ranging from 1% in some species to over 50% in others (Aghokeng et al.
The first isolates of SIVcpz were all derived from animals housed in primate centers or sanctuaries, although infection was rare in these populations. 2005), this finding raised doubts about whether chimpanzees represented a true SIV reservoir. These technical innovations, combined with genotyping methods for species and subspecies confirmation as well as individual identification, permitted a comprehensive analysis of wild-living chimpanzee populations throughout central Africa.