This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Introduction: Primate lentiviruses co-evolved with their host species and have extensive evidence of cross-species transmission. Two species of mangabeys were described to date to harbor SIVs: sooty mangabeys (SIVsm) and red-capped mangabeys (SIVrcm). These two viruses cluster in two different lineages. SIVagi isolated from agile mangabeys in Cameroon were philogenetically and biologically characterized in order to investigate the evolution of lentiviruses in mangabeys. Methods: Blood from 10 captive household pet agile mangabeys was tested at Centre Pasteur Cameroon for anti-SIV antibody using ELISA and Western Blot. V3 and gp36 reactivity for SIVs from major lineages were tested by peptide EIA. Virus cultures were done on agilis PBMCs, human PBMCs and cell lines. Co-receptor use of the isolated strain was investigated and CCR-5 sequencing was done to investigate delta-24 genotype of the tested monkeys. gag and pol fragments were amplified and phylogeneticly analyzed. Results and discussion: Two out the ten monkeys (20%) had antibody. Peptide assays showed no reaction on the V3 peptides and SIVrcm gp36 reactivity for both samples. Cultures of the PBMCs of one of these monkeys (703) were positive. This virus strain was grown on human PBMCs. No monkeys had the delta-24 bp deletion. However, preliminary data suggests that the SIVagiCam703 used CCR-2 for viral entry, similar to the SIVrcm. Phylogenetic analysis showed that SIVagi clusters within SIVrcm lineage in both analyzed regions at the TNPRC. We have currently sequenced a 4,500 bp encompassing LTR-pol, and further analysis is in progress. Agile monkeys are naturally infected with a distinct SIVagi. This virus was cross-transmitted from SIVrcm, which is supported by phylogenetic analyses. This cross-species transmission seems to be recent, as the cross-transmitted virus still uses the CCR-2 co-receptor for virus entry, in spite of the low frequency of CCR-5 delta-24 in the agile mangabeys. SIVagi represent new piece in the puzzle of lentiviral diversity and pathogenesis. Long-term follow-up is necessary to characterize the pathogenic potential of this cross-transmitted virus in agile monkeys.
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