Abstract
BackgroundD-type simian retrovirus-2 (SRV-2) causes an AIDS-like immune deficiency syndrome (SAIDS) in various macaque species. SAIDS is often accompanied by retroperitoneal fibromatosis (RF), an aggressive fibroproliferative disorder reminiscent of Kaposi's sarcoma in patients with HIV-induced AIDS. In order to determine the association of SRV-2 subtypes with SAIDS-RF, and study the evolution and transmission of SRV-2 in captive macaque populations, we have molecularly characterized the env gene of a number of SRV-2 isolates from different macaque species with and without RF.ResultsWe sequenced the env gene from eighteen SRV-2 isolates and performed sequence comparisons and phylogenetic analyses. Our studies revealed the presence of six distinct subtypes of SRV-2, three of which were associated with SAIDS-RF cases. We found no association between SRV-2 subtypes and a particular macaque species. Little sequence variation was detected in SRV-2 isolates from the same individual, even after many years of infection, or from macaques housed together or related by descent from a common infected parent. Seventy-two amino acid changes were identified, most occurring in the larger gp70 surface protein subunit. In contrast to the lentiviruses, none of the amino acid variations involved potential N-linked glycosylation sites. Structural analysis of a domain within the gp22/gp20 transmembrane subunit that was 100% conserved between SRV-2 subtypes, revealed strong similarities to a disulfide-bonded loop that is crucial for virus-cell fusion and is found in retroviruses and filoviruses.ConclusionOur study suggests that separate introductions of at least six parental SRV-2 subtypes into the captive macaque populations in the U.S. have occurred with subsequent horizontal transfer between macaque species and primate centers. No specific association of a single SRV-2 subtype with SAIDS-RF was seen. The minimal genetic variability of the env gene within a subtype over time suggests that a strong degree of adaptation to its primate host has occurred during evolution of the virus.
Highlights
D-type simian retrovirus-2 (SRV-2) causes an AIDS-like immune deficiency syndrome (SAIDS) in various macaque species
We have previously identified the macaque homolog of Kaposi's sarcomaassociated herpesvirus (KSHV), called retroperitoneal fibromatosis (RF)-associated herpesvirus (RFHV), in simian retroviruses (SRV)-2 associated RF lesions [23] suggesting that RFHV may play an etiologic role in simian acquired immune deficiency syndrome (SAIDS)-RF
We have analyzed the deduced amino acid sequences from these isolates and have compared them with the complete env gene sequences previously identified for an SRV-1 isolate from a rhesus macaque from the California National Primate Research Centers (NPRC) (D1/RHE/CA; [6]), an SRV-3 isolate from a rhesus macaque from the Wisconsin NPRC (D3/RHE/WI; [2]), an SRV-2 isolate from a Celebes black macaque (D2/CEL/OR; [14]), and two closely related SRV-2 isolates from rhesus macaques (D2/ RHE/OR and D2/RHE/OR/V1; [15,16]) from the Oregon NPRC
Summary
D-type simian retrovirus-2 (SRV-2) causes an AIDS-like immune deficiency syndrome (SAIDS) in various macaque species. In order to determine the association of SRV-2 subtypes with SAIDS-RF, and study the evolution and transmission of SRV-2 in captive macaque populations, we have molecularly characterized the env gene of a number of SRV-2 isolates from different macaque species with and without RF. Type D simian retroviruses (SRV) are Betaretroviruses which have been etiologically linked to a simian acquired immune deficiency syndrome (SAIDS) of varying severity in several Asian macaque species. All of the Type D SRVs are genetically and serologically related to the original prototype, the Mason-Pfizer monkey virus (MPMV), which was isolated from breast tumor tissue of a rhesus macaque (M. mulatta) in 1970 [1]. MPMV belongs to the SRV-3 serogroup and has been completely sequenced [2]. The prototype SRV genomic structure consists of only four genes flanked by LTRs on the 3' and 5' ends: the gag,prt,pol, and env genes encode the viral core proteins, the viral protease, the reverse transcriptase/ endonuclease/integrase, and the envelope glycoproteins, respectively
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