CHARACTERIZATION OF A NEW SIV FROM AGILE MANGABEY (CERCOCEBUS AGILIS)

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。引言：灵长类慢病毒与其宿主物种共同进化，并有广泛的跨物种传播证据。迄今为止，有两种白眉猴被描述为携带SIV：红顶白眉猴（SIVsm）和红顶白眉猴（SIVrcm）。这两种病毒聚集在两个不同的谱系中。从喀麦隆敏捷白眉猴中分离的SIVagi进行了遗传学和生物学特征鉴定，以研究白眉猴慢病毒的进化。方法：在喀麦隆巴斯德中心，采用ELISA和Western Blot检测10只圈养家养宠物敏捷白眉猴的血液中抗SIV抗体。通过肽EIA测试来自主要谱系的SIV的V3和gp 36反应性。在agilis PBMC、人PBMC和细胞系上进行病毒培养。研究分离菌株的共受体使用，并进行CCR-5测序以研究受试猴的delta-24基因型。扩增gag和pol片段并进行遗传学分析。结果和讨论：10只猴子中有2只（20%）有抗体。肽测定显示两种样品的V3肽和SIVrcm gp 36反应性上无反应。其中1只猴（703）的PBMC培养物呈阳性。该病毒株在人PBMC上生长。没有猴子有delta-24 bp缺失。然而，初步数据表明，SIVagiCam 703使用CCR-2进行病毒进入，类似于SIVrcm。系统发育分析表明，SIVagi集群内SIVrcm谱系在两个分析区域在TNPRC。我们目前已经测序了包含LTR-pol的4，500 bp，进一步的分析正在进行中。敏捷的猴子自然感染了一种独特的SIVagi。这种病毒是从SIVrcm交叉传播的，这是支持系统发育分析。这种跨物种传播似乎是最近的，因为交叉传播的病毒仍然使用CCR-2辅助受体进行病毒进入，尽管CCR-5 delta-24在敏捷白眉猴中的频率很低。SIVagi代表了慢病毒多样性和发病机制难题中的新部分。长期随访是必要的，以表征这种交叉传播病毒在敏捷猴中的致病潜力。

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.