Epidemiology of HIV-1/HIV-2 Dual Infection

描述(由申请人提供)：本申请名为分子 HIV-2和HIV-1/HIV-2双重感染的流行病学和病毒演变 塞内加尔的个人，K08指导的临床科学家发展 该奖项将有助于在杰弗里·S·戈特利布博士的赞助下， 詹姆斯·I·穆林斯和华盛顿大学学院的合作者 医学院和塞内加尔达喀尔大学，以获得必要的技能 继续追求这项研究计划的近期目标以及 继续他的道路，成为一名创新和富有成效的独立学者 作为一名内科科学家的研究生涯。 对人类多样性和进化的全球理解 免疫缺陷病毒(HIV)对开发预防性药物将是重要的 疫苗接种和对艾滋病发病机制的了解。尽管在结构上和 在基因上相似的HIV-1和HIV-2的表现截然不同，都是在 作为全球流行病的病原体，患者的个体水平也不高。这个 造成这种情况的原因尚不清楚。有证据表明，患者具有两面性 同时感染艾滋病毒-1和艾滋病毒-2的人可以更好地控制自己的病毒负担。 我们纵向跟踪了一群感染病毒的塞内加尔人 HIV-1和/或HIV-2提供了一个独特的机会来研究 西非艾滋病的分子流行病学和进化动力学 将它们与病毒学、免疫学和临床结果相关联。此应用程序 我将检验以下假设：1)如果在患者内部，艾滋病毒-2病毒 多样性和差异性将比HIV-1和 如果以病毒分化和多样性衡量的艾滋病毒进化速度， 在双重感染的人中将会较慢。CXCR4的出现 HIV-1变异体在双重感染者中是否会延迟 这些事件与免疫状态、病毒载量和临床结果相关； 2)HIV-1之间的交叉反应免疫反应和病毒干扰 而HIV-2选择在双重感染中感染独特的HIV-1亚型 个人；以及3)重组HIV-1/HIV-2病毒是否可以双重出现 感染的个体，如果他们这样做了，他们是否改变了 这些人中的艾滋病毒感染。

DESCRIPTION (provided by applicant): This application, entitled Molecular Epidemiology and Viral Evolution in HIV-2 and HIV-1/HIV-2 Dually Infected Individuals in Senegal, for a K08 Mentored Clinical Scientist Development Award, will help enable Dr. Geoffrey S. Gottlieb, under the sponsorship of Dr. James I. Mullins and collaborators at the University of Washington School of Medicine and the University of Dakar, Senegal, to acquire the skills necessary to continue to pursue the immediate goals of this research plan as well as to continue his path toward an innovative and productive independent academic research career as a physician-scientist. A global understanding of the diversity and evolution of Human Immunodeficiency Viruses (HIVs) will be important to developing prophylactic vaccines and understanding the pathogenesis of AIDS. Although structurally and genetically similar, HIV-1 and HIV-2, behave quite differently, both at the level of the individual patient and as agents of the global epidemic. The reasons for this are not clear. Evidence suggests that patients dually infected with both HIV-1 and HIV-2 have greater control of their viral burden. Our longitudinally followed cohort of Senegalese individuals whom are infected with HIV-1, HIV-2 or both viruses provides a unique opportunity to study the molecular epidemiology and evolutionary dynamics of AIDS in West Africa and to correlate them with virologic, immune and clinical outcomes. This application will examine the following hypotheses: 1) If intra-patient, HIV-2 viral diversity and divergence will be attenuated compared to that seen in HIV-1 and if the rate of HIV evolution, as measured by viral divergence and diversity, will be slower in dually infected individuals. Whether emergence of CXCR4 HIV-1 variants will be delayed in dually infected individuals and whether these events correlate with immune status, viral load and clinical outcomes; 2) That cross-reactive immune responses and viral interference between HIV-1 and HIV-2 selects for infection with unique HIV-1 subtypes in dually infected individuals; and 3) If recombinant HIV-1/HIV-2 viruses can emerge in dually infected individuals and if they do, whether they alter the natural history of HIV infection in these people.