Primate innate immune defense and adaptation to SIV/HIV infection.

详细信息   

• 作者：Sterner ; Kirstin N.
• 学历：Doctor
• 年：2009
• 导师：Disotell, Todd R.,eadvisorDi Fiore, Anthony F.ecommittee memberJolly, Clifford J.ecommittee memberWildman, Derek E.ecommittee memberRaaum, Ryan L.ecommittee member
• 毕业院校：New York University
• Department：Anthropology
• ISBN：9781109259148
• CBH：3365753
• Country：USA
• 语种：English
• FileSize：78904366
• Pages：328

文摘

In order to understand why SIV/HIV infection is non-pathogenic in some primate species it is important to consider both the molecular mechanisms behind chronic immune activation and the evolutionary history of these systems. Toll-like receptor (TLR) signaling pathways are one of the initial regulators of immune response to HIV infection and therefore represent an appropriate target for study. Byproducts of TLR signaling have the potential to continually activate immune cells and may play a role in initiating and maintaining chronic immune activation in SIV/HIV hosts (like humans) that progress to AIDS. This dissertation examines the evolutionary history of genes involved in the TLR7(9)/IRF7-dependant signaling pathway in primates in an effort to determine whether co-evolution between SIV strains and African non-human primates has shaped the evolution of these genes. This research introduces an evolutionary perspective to a problem that has been largely addressed from the molecular and cellular biology perspective by examining why SIV infection progresses to AIDS in some primate species. This dissertation provides the first evidence suggesting positive selection on Toll-like receptor 7 (TLR7), interferon-regulatory factor 7 (IRF7) and osteopontin (SPP1). This dissertation also provides the first evidence suggestive of adaptive evolution in humans on interleukin-1 receptor-associated kinase 1 ( IRAK1), a protein kinase necessary for IRF7 activation.