Stop playing Whac-A-Mole with HIV: A promising new therapeutic strategy.

Due to the HIV’s capacity to hide into different cell reservoirs, an effective therapy would be to reduce the viral load and limit the virus’s resurgence in the event of treatment interruption. Over the past couple of decades, various strategies have been developed to reduce the viral load in HIV+ patients. Presently, ART is the main therapy used to reduce the viral load in HIV+ patients. While very effective, this therapy has numerous side effects. To maintain a low viral burden patients must maintain treatment as the viral load will quickly rebound should a patient cease ART. Thus, any strategy that would decrease the chance of the virus being able to rebound could almost be considered as a form of a cure. 

There are two main therapeutic strategies currently being studied to inhibit the virus’s ability to re-emerge in patients. These strategies are the “block-and-lock” and the “shock-and-kill”. The goal of the block-and-lock strategy is to inhibit (block) the progression of the provirus to an actual viral infection by targeting different transcription pathways. Doing this, the virus is locked in the provirus state. (1) The second strategy, shock-and-kill, aims to force the latent virus to present itself (shock) thereby allowing therapeutics to neutralize virus reservoir infected cells. (2)

One mechanism by which HIV is able to hide from immune recognition is through the down regulation of the T-cell marker CD4 on the host cell. In infected T-cells, host CD4 molecules interact with viral Env proteins. This interaction exposes HIV infected cells such that natural anti-HIV antibodies are able to recognize and neutralize infected cells. To circumvent this recognition, HIV employs the viral protein Nef and VPU to down regulate CD4 expression thereby reducing the exposure of the virus on these cells. Recently, Rajashekar et al. demonstrated a promising strategy to exploit the CD4-Env interaction to expose and eliminate viral infected cells. (3) The team, led by Dr. Andres Finzi, treated virus-infected cells with a small CD4 mimetic compound (CD4mc) that was able to interact with viral Env and immunologically expose these cells. As a result, infected cells treated with CD4mc sensitized infected cells to naturally present antibodies and reduced the viral reservoir in HIV-infected humanized mice.

Important studies aiming at reducing the viral reservoir or locking the virus in provirus form are currently our best chance to stop playing Whac-A-Mole with HIV. We at MédiMabs are continually helping HIV researchers by providing custom services and a variety of HIV-related antibodies.

Written by
MédiMabs’ Team