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.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Philipp-Staheli
Jeannette
J
Department of Pathobiology, School of Public Health and Community Medicine, University of Washington, Seattle, Washington, USA. jstaheli@u.washington.edu
Marquardt
Taya
T
Thouless
Margaret E
ME
Bruce
A Gregory
AG
Grant
Richard F
RF
Tsai
Che-Chung
CC
Rose
Timothy M
TM
D000595:Amino Acid Sequence; D000818:Animals; D015967:Gene Expression Regulation, Viral; D014644:Genetic Variation; D008251:Macaca / Q000821:virology*; D016093:Mason-Pfizer monkey virus / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D010802:Phylogeny; D012185:Retroperitoneal Fibrosis / Q000150:complications* / Q000821:virology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications*; D013045:Species Specificity; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics*
D014759:Viral Envelope Proteins