Single Molecule Imaging of Human Immunodeficiency Virus Type-1 (HIV-1) Envelope Glycoprotein Dynamics Identifies Viral Elements Contributing to Infectious Particle Assembly

The Human Immunodeficiency Virus Type-1 (HIV-1) has remained highly prevalent across the world for over 40 years, taking lives by attacking the immune system. There remains a lack of universal treatment options, which can be attributed to a poorly understood process in the life cycle of the virus: the assembly of new infectious virion, which propagate the infection within a host. Though it is known that the viral spike glycoprotein, Envelope (Env), responsible for viral entry into a host immune cell, is essential in propagation of infection, the mechanism of its incorporation into newly assembling infectious particles remains ill understood. We observe, in real time, Env incorporation events into newly assembling viral buds, formed by the virus’ structural glycoprotein, Gag, and have identified several viral elements in both Env and Gag that demonstrate a contribution towards assembly of an infectious HIV-1 virus particle. Notably, our observations support a mechanism of direct interaction between Env and Gag during viral assembly, with critical residues identified in domains of both proteins where the two proteins are likely to interface – in the Env cytoplasmic tail, and the Gag matrix domain. Identification of these and other critical viral elements during assembly of infectious virion could open the door to methods and therapeutics in abolishing the spread of this deadly viral infection