NIH Research Festival
FARE Award Winner
HIV remains one of the most variable viruses due to its high mutation rate, in particular in the envelope encoded by env. As a result, these quick changes allow the virus to evade the host immune responses that target predominantly viral surface proteins. HIV envelope plays a critical role in HIV infection as only in the right conformation of Env HIV is able to bind to cell receptors/coreceptors and to fuse with the plasma membrane. On each virion there are 13 or 14 spikes. To determine whether on a given virion all the spikes are either functional, defective, or mosaic with respect to carrying both functional and non-functional Envs, it is necessary to analyze individual virions. Here, we applied a new technique “flow virometry” to address this problem. Individual virions were captured with 15-nm magnetic nanoparticles and stained with antibodies against Envs in different conformations. We found that on the majority of virions there are either only functional Envs or predominantly defective Envs. There was little or no contribution of mosaic virions to infection of human tissue ex vivo. The lack of mosacism for the majority of infectious virions may aid HIV immune evasion by subverting of humoral responses to generate non-neutralizing antibodies at no cost to infectious virions. Induction of antibodies targeting functional Envs is critical for the development of effective prophylactic strategies.
Scientific Focus Area: Virology
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