NEF GENE EVOLUTION FROM A SINGLE TRANSMITTED STRAIN IN ACUTE SIV INFECTION

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 中心，但不一定是研究者所在的机构。 目的： 使用非人灵长类动物HIV-1/AIDS模型测试我们的HIV-1原发感染模型的有效性。 为了研究SIV感染急性期单个传播毒株的nef基因的进化，我们采用单基因组扩增的方法对全长nef基因进行了纵向测序。免疫缺陷病毒感染的急性期在人类和非人灵长类动物中确定稳态病毒载量和随后的疾病进展中起着至关重要的作用。最近，我们开发了一种蒙特-卡罗模拟与数学分析的病毒演变过程中的主要HIV-1感染，使新的HIV-1感染的分类起源于多个与单一传播的病毒株和估计的时间经过感染后。 结果如下：在用SIVmac 239克隆实验性感染两只恒河猴后的前3周内收集的总共207个SIV nef SIV序列进行了分析，发现显示出可比较的遗传多样性水平，0%至0.053%，与急性HIV-1感染的env序列的遗传多样性水平，0.005%至0.127%。我们证实了急性HIV-1感染模型正确地将恒河猴中的实验性SIV感染鉴定为由单一创始者菌株引发的“同质”感染。结果表明，所采集菌株的共有序列与模型预测的传递序列一致.然而，在感染后第7天、第11天和第18天测量的多样性连续下降违反了模型假设，即没有任何选择的中性进化。虽然nef基因的进化在前3周的SIV感染起源于一个单一的传播菌株显示出可比的序列进化率在急性HIV-1感染期间观察到的，一个纯化的选择的创始人nef基因在早期阶段的实验感染的非人灵长类动物。 这项研究使用了WNPRC Immulogy & Virology and Genetics Services。 出版物： Bimber BN，Chugh P，Giorgi EE，Kim B，Almudevar AL，Dewhurst S，奥康纳DH，Lee HY.急性SIV感染中来自单一传播毒株的Nef基因进化逆转录病毒2009年6月8日;6：57。

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. Objective: To test the validity of our primary HIV-1 infection model using a non-human primate model for HIV-1/AIDS. To examine evolution of the viral nef genes from a single transmitted strain during the acute phase of SIV infection, we sequenced full-length nef genes longitudinally using the method of single genome amplification. The acute phase of immunodeficiency virus infection plays a crucial role in determining steady-state virus load and subsequent progression of disease in both humans and nonhuman primates. Recently we developed a Monte-Carlo simulation with mathematical analysis of viral evolution during primary HIV-1 infection that enables classification of new HIV-1 infections originating from multiple versus single transmitted viral strains and the estimation of time elapsed following infection. Results: A total of 207 SIV nef SIV sequences, collected during the first 3 weeks following experimental infection of two rhesus macaques with the SIVmac239 clone, were analyzed and found to display a comparable level of genetic diversity, 0% to 0.053%, with that of env sequences from acute HIV-1 infection, 0.005% to 0.127%. We confirmed that the acute HIV-1 infection model correctly identified the experimental SIV infections in rhesus macaques as "homogenous" infections, initiated by a single founder strain. The consensus sequence of the sampled strains corresponded to the transmitted sequence as the model predicted. However, measured sequential decrease in diversity at day 7, 11, and 18 post infection violated the model assumption, neutral evolution without any selection. While nef gene evolution over the first 3 weeks of SIV infection originating from a single transmitted strain showed a comparable rate of sequence evolution to that observed during acute HIV-1 infection, a purifying selection for the founder nef gene was observed during the early phase of experimental infection of a nonhuman primate. This research used WNPRC Immulogy & Virology and Genetics Services. PUBLICATION: Bimber BN, Chugh P, Giorgi EE, Kim B, Almudevar AL, Dewhurst S, O'Connor DH, Lee HY. Nef gene evolution from a single transmitted strain in acute SIV infection. Retrovirology. 2009 Jun 8;6:57.