Characterization of Binding and Fusion Efficiencies Mediated by the V1-V5 Env Derived from Transmitted and Non-transmitted Viruses Isolated from a Perinatal Transmission Cohort from Zambia

Abstract

Human Immunodeficiency Virus Type 1 (HIV-1) is the etiological agent of acquired immunodeficiency syndrome (AIDS), which affects over 34 million people worldwide. In sub-Saharan Africa where access to antiretroviral therapies (ART) is limited, mother-to-child transmission (MTCT) rates remain high and represent a major concern in the global HIV/AIDS epidemic. Little is known about the biological properties of viruses that are transmitted perinatally, including how the biological functions of envelope (Env) influence transmissibility. Previously, transmitted viruses were found to have an advantage in replicative fitness mediated by Env V1-V5. In this study viruses derived from transmitting mother infant pairs (MIPs) were used to determine if the binding and fusion activities are influenced by Env V1-V5 and if any differences correlate to replicative fitness and transmission. Fusion and binding assays were used to measure the biological functions of Env from individual clones of five MIP. RESULTS: Neither binding nor fusion is predictive of transmission. However, clonal variation in both functions is observed, demonstrating V1-V5 is capable of influencing fusion and binding. Fusion correlates with infectivity, but does not correlate with binding. The results of this study have provided new insights to better understand the functional properties of Env and its role in MTCT. Advisor: Charles Woo