SIV Transmission in Male NHP

描述（由申请人提供）：艾滋病毒主要通过异性性接触传播，全世界感染该病毒的男女人数大致相等。已经开展了许多研究，以确定HIV传播的生物学特性，目的是确定从粘膜病毒传播到远端淋巴组织传播过程中的各个阶段，这些阶段可以被疫苗接种中断。在很大程度上，这项工作的重点是了解艾滋病毒向妇女的传播情况，很少努力确定通过插入性阴茎性交接触艾滋病毒的男子的传播和传播情况。我们最近开发了一个可靠的模型，阴茎艾滋病毒传播使用SIV接种成熟雄性恒河猴。该模型概括了HIV在男性中传播的关键病毒学和流行病学特征，即当接种剂被放入包皮而不是简单地放在阴茎头和阴茎轴上时，男性传播效率最高；并且在传播后立即在血浆中发现单一病毒变体（Keele， Miller未发表，见初步研究）。我们已经确定了SIVmac251在恒河猴阴道传播的病毒学和免疫学特征，在本应用中，我们建议进行阴茎SIV传播的平行研究。这些研究将有助于更好地了解HIV是如何通过阴茎性交传播给男性的，以及存在于阴茎粘膜表面的抗病毒效应机制的范围，而阴茎粘膜表面是病毒传播的场所。需要这些信息来合理设计疫苗，以引起男性生殖道的免疫反应，从而限制或预防艾滋病毒的传播

DESCRIPTION (provided by applicant): HIV is primarily transmitted by heterosexual contact and approximately equal numbers of men and women are infected with the virus worldwide. Numerous studies to define the biology of HIV transmission have been undertaken with the goal of identifying stages in the processes from mucosal virus transmission through dissemination to distal lymphoid tissues that can be interrupted by vaccination. To large extent this effort has focused on understanding transmission of HIV to women with little effort define the transmission and dissemination in men exposed to HIV by insertive penile intercourse. We recently developed a reliable model of penile HIV transmission using SIV inoculation of mature male rhesus macaques. This model recapitulates the key virologic and epidemiologic features of HIV transmission in men, i.e. transmission is most efficient in to males when the inoculum is placed into the foreskin rather than simply onto the glans and shaft of the penis; and a single viral variant is found in plasma immediately after transmission (Keele, Miller Unpublished and see Preliminary Studies). We have characterized the virology and immunology of vaginally transmitted SIVmac251 in rhesus monkeys and in this application we propose to conduct parallel studies of penile SIV transmission. The studies will lead to a better understanding of how the HIV is transmitted to males by penile intercourse and the range of antiviral effector mechanisms that are present in the penile mucosal surfaces that are the sites of virus transmission. This information is required to rationally design vaccines to elicit immune responses in the male genital tract that can limit or prevent HIV transmission