The gp120 molecule of HIV-1 is a glycoprotein that is part of the outer layer of the virus. It presents itself as viral membrane spikes consisting of 3 molecules of gp120 linked together and anchored to the membrane by gp41 protein. Gp120 is essential for viral infection as it facilitates HIV entry into the host cell and this is its best-known and most researched role in HIV infection. However, it is becoming increasingly evident that gp120 might also be facilitating viral persistence and continuing HIV infection by influencing the T cell immune response to the virus. Several mechanisms might be involved in this process of which gp120 binding to the CD4 receptor of T cells is the best known and most important interaction as it facilitates viral entry into the CD4+ cells and their depletion, a hallmark of the HIV infection. Gp120 is shed from the viral membrane and accumulates in lymphoid tissues in significant amounts. Here, it can induce apoptosis and severely alter the immune response to the virus by dampening the antiviral CTL response thus impeding the clearance of HIV. The effects of gp120 and how it interacts and influences T cell immune response to the virus is an important topic and this review aims to summarize what has been published so far in hopes of providing guidance for future work in this area.

This is the first demonstration of a novel approach that exploits T-cell chemorepulsion to induce site specific immune isolation and thereby overcomes allograft rejection without the use of systemic immunosuppression.

Gp120 is a critical component of the envelope of HIV-1. Its role in viral entry is well described. In view of its position on the viral envelope, gp120 is a part of the retrovirus that immune cells encounter first and has the potential to influence antiretroviral immune responses. We propose that high levels of gp120 are present in tissues and may contribute to the failure of the immune system to fully control and ultimately clear the virus. Herein, we show for the first time that lymphoid tissues from acutely HIV-1/SIV (SHIV)-KB9-infected macaques contain deposits of gp120 at concentrations that are high enough to induce suppressive effects on T cells, thus negatively regulating the antiviral CTL response and contributing to virus survival and persistence. We also demonstrate that SHIV-KB9 gp120 influences functional T cell responses during SHIV infection in a manner that suppresses degranulation and cytokine secretion by CTLs. Finally, we show that regulatory T cells accumulate in lymphoid tissues during acute infection and that they respond to gp120 by producing TGFβ, a known suppressant of cytotoxic T cell activity. These findings have significant implications for our understanding of the contribution of non-entry-related functions of HIV-1 gp120 to the pathogenesis of HIV/AIDS.

The gp160 complex of the envelope of the HIV virus and its component gp120 are essential for viral entry into the host cell. Gp120 binding to its receptor CD4 and co-receptor, CXCR4 or CCR5 is required for fusion of viral and cellular membranes. The presence of gp120 facilitates immune escape of the virus through its profound effect on the immune cells. It is a polyclonal activator of B cells, causing them to differentiate into immunoglobulin producing cells while activating the complement cascade. This results in the formation of immune complexes that are unable to kill the virus but instead shield it from the attack of other immune cells. Such HIV-1 virus that is trapped within immune complexes and is bound to the B cells via CD21 is more infectious than the free virion. In addition, HIV virions are trapped on the membrane of follicular dendritic cells (FDC) processes in immune complexes or through complement receptors. Thus, FDC can serve as a 'Trojan horse' and transmit the trapped virus to CD4+ T lymphocytes as they migrate through the germinal centre to the follicular mantle and paracortical areas. It was demonstrated that CXCR4-binding HIV-1 X4 gp120 causes the movement of T cells, including HIV-specific CTL, away from high concentrations of the viral protein and its expression by target cells reduces CTL efficacy in vitro. Therefore, apart from the essential role in viral attachment and infection of cells, gp120 possesses several properties that affect the behavior of immune cells and skew the immune response to the virus facilitating viral escape.