Phylogeny and History of the Lost SIV from Crab-Eating Macaques: SIVmfa

Abstract

In the 20th century, thirteen distinct human immunodeficiency viruses emerged following independent cross-species transmission events involving simian immunodeficiency viruses (SIV) from African primates. In the late 1900s, pathogenic SIV strains also emerged in the United Sates among captive Asian macaque species following their unintentional infection with SIV from African sooty mangabeys (SIVsmm). Since their discovery in the 1980s, SIVs from rhesus macaques (SIVmac) and pig-tailed macaques (SIVmne) have become invaluable models for studying HIV pathogenesis, vaccine design and the emergence of viruses. SIV isolates from captive crab-eating macaques (SIVmfa) were initially described but lost prior to any detailed molecular and genetic characterization. In order to infer the origins of the lost SIVmfa lineage, we located archived material and colony records, recovered its genomic sequence by PCR, and assessed its phylogenetic relationship to other SIV strains. We conclude that SIVmfa is the product of two cross-species transmission events. The first was the established transmission of SIVsmm to rhesus macaques, which occurred at the California National Primate Research Center in the late 1960s and the virus later emerged as SIVmac. In a second event, SIVmac was transmitted to crab-eating macaques, likely at the Laboratory for Experimental Medicine and Surgery in Primates in the early 1970s, and it was later spread to the New England Primate Research Center colony in 1973 and eventually isolated in 1986. Our analysis suggests that SIVmac had already emerged by the early 1970s and had begun to diverge into distinct lineages. Furthermore, our findings suggest that pathogenic SIV strains may have been more widely distributed than previously appreciated, raising the possibility that additional isolates may await discovery.

Structural diversity of the region encompassing DIS, SD and Psi hairpins in HIV and SIV genomes

“…The last group of SIV genomes with certain similar features consists of lineages smm, mac, mne and stm. SIVsmm infecting sooty mangabeys is the origin of HIV-2 and all these SIV lineages ( McCarthy et al. 2016 and refs therein; Sharp and Hahn 2011 ).…”

Walk on the wild side: SIV infection in African non-human primate hosts—from the field to the laboratory

“…HIV-2, comprising eight groups, originated following eight cross-species transmissions of SIVsmm from sooty mangabeys ( 72 – 76 ). Interestingly, SMs naturally infected with SIVsmm were the origin of the major reference strains in macaques ( 77 , 78 ), following accidental transmissions that occurred during kuru ( 79 ) and leprosy ( 80 ) experiments carried out in the 1970s in the National Primate Research Centers in the US ( 81 ). This accidental experimental transmission of these viruses (which involved serial passages) is probably the reason for their high pathogenicity in macaques ( 82 ).…”

So Pathogenic or So What?—A Brief Overview of SIV Pathogenesis with an Emphasis on Cure Research

“…Furthermore, studies have shown [22] that the same experiments carried out at the CNPRC were likely responsible for the infection of SIVs of different other species of macaques, such as the pigtailed macaques (Macaca nemestrina) [24] and the stumptailed macaque (Macaca arctoides) [25,26] and crab eating macaque (Macaca fascicularis) [27]. The progenitor viruses were from sooty mangabeys at the CNPRC which were used for kuru experiments, allowing for serial passaging and eventual establishment of the SIVmac239 and SIVmac251 isolates.…”

“…Furthermore, studies have shown [22] that the same experiments carried out at the CNPRC were likely responsible for the infection of SIVs of different other species of macaques, such as the pigtailed macaques (Macaca nemestrina) [24] and the stumptailed macaque (Macaca arctoides) [25,26] and crab eating macaque (Macaca fascicularis) [27].…”