Human immunodeficiency virus type 1 envelope glycoprotein gp120–trans-activator of transcription protein interaction (gp120–Tat interaction)

The HIV-1 gp120–Tat interaction involves the binding of the extracellular trans-activator of transcription (Tat) protein to the gp120 subunit of the viral envelope (Env) complex (Monini et al., 2012, PLoS ONE). Although Tat is primarily an intracellular regulatory protein, it is actively secreted by infected cells and can bind to virions, significantly enhancing their infectivity and ability to enter target cells (Ensoli et al., 2021, Frontiers in Immunology). This interaction facilitates the recruitment of the virus to the cell surface and may help the virus evade neutralizing antibodies directed at the Env protein alone (Lusso et al., 2021, Journal of Virology). Therapeutic strategies targeting this interaction focus on neutralizing extracellular Tat to prevent its binding to gp120, thereby reducing the efficiency of viral transmission and spread (Ensoli et al., 2015, Retrovirology). Clinical trials have explored Tat-based vaccines as a means to elicit antibodies that disrupt this interaction and improve outcomes in HIV-positive individuals (Cafaro et al., 2019, Nature Communications). By inhibiting this specific protein-protein interaction, researchers aim to provide a synergistic effect alongside traditional antiretroviral therapies. The interaction is considered a critical component of the natural infection process that is not fully addressed by current Env-only vaccine candidates.

Other names

Tat-Env interactionTat-gp120 bindingExtracellular Tat-Env complexTat-gp120 interaction

The mechanism involves the use of antibodies to bind to the extracellular Tat protein, specifically its basic domain, thereby preventing it from interacting with the gp120 subunit of the HIV-1 envelope complex. This blockade inhibits Tat-mediated enhancement of viral entry and reduces the efficiency of infection in target cells (Monini et al., 2012; Ensoli et al., 2021).