SIV Transmission in Male NHP

描述（由申请人提供）：艾滋病毒主要通过异性接触传播，全世界感染该病毒的男性和女性人数大致相同。已经进行了许多定义HIV传播生物学的研究，目的是确定从粘膜病毒传播到传播到远端淋巴组织的过程中的阶段，这些阶段可以通过接种疫苗中断。在很大程度上，这一努力侧重于了解艾滋病毒向妇女的传播，而很少努力确定通过插入阴茎性交在暴露于艾滋病毒的男子中的传播和传播。我们最近开发了一个可靠的阴茎HIV传播模型，使用SIV接种成熟的雄性恒河猴。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，即当接种物置于包皮中而不是简单地置于阴茎头和阴茎干上时，传播对男性最有效;并且在传播后立即在血浆中发现单一病毒变体（Keele，米勒未发表，参见初步研究）。我们的特点是恒河猴阴道传播的SIVmac 251的病毒学和免疫学，并在此应用程序中，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艾滋病毒如何通过阴茎性交传播给男性，以及作为病毒传播部位的阴茎粘膜表面存在的抗病毒效应机制的范围。这一信息是合理设计疫苗所必需的，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and shaft of the penis; and a single viral variant is found in plasma immediately after transmission (Keele, Miller Unpublished and see Preliminary Studies).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