Epidemiology of HIV-1/HIV-2 Dual Infection

说明（由申请人提供）： HIV-2和HIV-1/HIV-2双重感染者的流行病学和病毒进化 塞内加尔的个人，用于K 08指导临床科学家发展 奖，将有助于使博士杰弗里S。Gottlieb，在Dr. 詹姆士一世马林斯和华盛顿大学医学院的合作者们 医学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直接目标，以及 继续他的道路走向创新和富有成效的独立学术 作为一名物理学家兼科学家的研究生涯。 对人类多样性和进化的全球理解 免疫缺陷病毒（HIV）将是重要的发展预防 疫苗和了解艾滋病的发病机制。虽然结构和 基因相似的HIV-1和HIV-2，表现完全不同，两者都在 作为全球流行病的代理人。的 其原因尚不清楚。有证据表明，患者 同时感染HIV-1和HIV-2的人对他们的病毒负荷有更好的控制。 我们对感染艾滋病病毒的塞内加尔人进行了纵向跟踪 与HIV-1、HIV-2或这两种病毒的结合提供了研究HIV-1、HIV-2或这两种病毒的独特机会 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、免疫和临床结果相关联。本申请 将检验以下假设：1）如果患者体内，HIV-2病毒 与HIV-1相比，多样性和分歧将减弱， 如果艾滋病毒进化的速度，以病毒的分化和多样性来衡量， 在双重感染者中会更慢。CXCR 4的出现 HIV-1变异体在双重感染者中会延迟， 这些事件与免疫状态、病毒载量和临床结果相关; 2)交叉反应性免疫反应和HIV-1之间的病毒干扰 而HIV-2在双重感染者中选择感染独特的HIV-1亚型， 3）如果重组HIV-1/HIV-2病毒可以出现在双重个体中， 感染的个体，如果他们这样做，他们是否改变了自然历史， 这些人的艾滋病毒感染。

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.