Genetic variability of the envelope gene of Type D simian retrovirus-2 (SRV-2) subtypes associated with SAIDS-related retroperitoneal fibromatosis in different macaque species

• Published in: Virology journal Vol. 3; no. 1; p. 11
• Main Authors: Philipp-Staheli, Jeannette, Marquardt, Taya, Thouless, Margaret E, Bruce, A Gregory, Grant, Richard F, Tsai, Che-Chung, Rose, Timothy M
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 06.03.2006; BioMed Central; BMC
• Subjects: Amino Acid Sequence; Animals; Filovirus; Gene Expression Regulation, Viral; Genetic Variation; Human immunodeficiency virus; Lentivirus; Macaca; Macaca - virology; Mason-Pfizer monkey virus - genetics; Mason-Pfizer monkey virus - physiology; Molecular Sequence Data; Phylogeny; Primates; Retroperitoneal Fibrosis - complications; Retroperitoneal Fibrosis - virology; Retrovirus; Simian Acquired Immunodeficiency Syndrome - complications; Species Specificity; Viral Envelope Proteins - chemistry; Viral Envelope Proteins - genetics
• ISSN: 1743-422X; 1743-422X
• DOI: 10.1186/1743-422X-3-11

D-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. We 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. Our 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.