Abstract
Naturally circulating lentiviruses are abundant in African primate species today, yet their origins and history of transmitting between hosts remain obscure. As a means to better understand the age of primate lentiviruses, we analyzed primate genomes for signatures of lentivirus-driven evolution. Specifically, we studied the adaptive evolution of host restriction factor APOBEC3G (A3G) in Old World Monkey (OWM) species. We find recurrent mutation of A3G in multiple primate lineages at sites that determine susceptibility to antagonism by the lentiviral accessory protein Vif. Using a broad panel of SIV Vif isolates, we demonstrate that natural variation in OWM A3G confers resistance to Vif-mediated degradation, suggesting that adaptive variants of the host factor were selected upon exposure to pathogenic lentiviruses at least 5–6 million years ago (MYA). Furthermore, in members of the divergent Colobinae subfamily of OWM, a multi-residue insertion event in A3G that arose at least 12 MYA blocks the activity of Vif, suggesting an even more ancient origin of SIV. Moreover, analysis of the lentiviruses associated with Colobinae monkeys reveal that the interface of the A3G-Vif interaction has shifted and given rise to a second genetic conflict. Our analysis of virus-driven evolution describes an ancient yet ongoing genetic conflict between simian primates and lentiviruses on a million-year time scale.
Highlights
human immunodeficiency virus-type 1 (HIV-1) was introduced into human populations in the early 20th century following multiple transmissions of a chimpanzee virus, known as SIVcpz [1,2]
A growing list of apparently nonpathogenic, species-specific strains has been characterized in dozens of African primates, suggesting that primate lentiviruses are older and more widespread than originally thought
We report that the immunity factor APOBEC3G is evolving in tandem with the lentiviral accessory gene vif, allowing us to associate instances of host evolution with instances of lentivirus infection in deep and shallow timescales
Summary
HIV-1 was introduced into human populations in the early 20th century following multiple transmissions of a chimpanzee virus, known as SIVcpz [1,2]. The other, less virulent human lentivirus, HIV-2, resulted from transmissions of SIVsm, a virus found in sooty mangabeys [3]. More than 40 non-human primate species in sub-Saharan Africa are infected with species-specific strains of SIV [4]. Known as ‘‘natural hosts,’’ these species either co-evolved with their respective lentivirus or were infected more recently via cross-species transmission from other primates [5]. The association between natural hosts and SIV is thought to be considerably older than that of humans and HIV [6,7]. Natural SIV infections do not generally cause an AIDS-like immunodeficiency in their autologous host species, leading to the hypothesis that the virus-host relationship has evolved towards an apathogenic state [8,9,10,11]. The age and pathogenic potential of wild SIV infections in diverse primate taxa remain largely uncharacterized
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