LONGITUDINAL ANALYSIS OF HIV-1 CLADE C FITNESS

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Subtype C HIV-1 is now the most abundant and the most rapidly expanding subtype in the world. The envelope (Env) glycoprotein of HIV-1 is the primary determinant of viral tropism (receptor recognition) and fusion of viral and cellular membrane in viral entry. HIV-1 transmission is dependent on receptor binding and fusion functions of the envelope glycoprotein. Yet very little is known about the relationships between Env evolution, viral fitness, transmission, and disease progression, in the context of subtype C in children. The hypothesis is that HIV-1 fitness correlates with Env properties and evolves longitudinally with changes in the Env, and that high fitness viruses are preferentially transmitted from mothers to infants where they mediate more rapid disease progression. The overall objective is to determine the role of viral envelope in mother to child transmission and disease progression in the infected children, and how it relates to changes in the Env sequences. We have recently longitudinally characterized the evolution of the HIV-1 envelope gene from seven subtype C HIV-1 perinatally infected children with different clinical outcomes from Lusaka, Zambia. We found that viral diversity correlates with time of infection and are now in the process of constructing different proviral and Env expression constructs from these seven infected mother/ infant pairs. These chimeras are being characterized virologically to determine whether there are specific biological determinants/ functions of Env (fusion, virus entry, replication kinetics, neutralization sensitivity and replication capacity/fitness) that correlate with subtype C HIV-1 perinatal transmission or disease progression in infected children.