Mapping determinants in the gp41 CT of HIV‐1 Env that mediate resistance to antibody neutralization during cell‐cell infection.

Abstract

Human Immunodeficiency Virus Type 1 (HIV‐1) uses its surface envelope glycoprotein (Env) to mediate entry into CD4+ T‐cells. During direct T‐cell to T‐cell infection mediated by the virological synapse (VS), Env initiates cell‐cell adhesion in a CD4 dependent manner. Entry of viral capsids into a target cell resulting from this fusion can be blocked by neutralizing antibodies. However VS‐mediated infection is more resistant to neutralization compared to cell‐free infection. The transmembrane region of Env, gp41 has a cytoplasmic tail (CT) made up of 151 amino acids that has been shown to aid in the fusion process and play a role in HIV‐1's resistance to neutralizing antibodies during cell‐cell infection by regulating the exposure of neutralizing epitopes on the cell surface. Complete truncation of the gp41 CT makes VS‐mediated infection more sensitive to antibody neutralization. We hypothesize that specific structural features in the CT regulate HIV‐1 neutralization and certain amino acids correspond to the exposure of neutralizing epitopes. To map these putative conformation altering motifs, we constructed a series of C‐terminal truncations in the gp41 CT. Infectivity and neutralization assays are being performed to evaluate how these truncations affect HIV‐1's infectivity and its resistance to neutralizing antibodies during cell free and cell‐cell infection.