Persistent non-HIV pathogens: important drivers of HIV-1 persistence?

In the last years the HIV-1 cure research evolved enormously, however, an HIV-1 cure still remains a challenge. This is mainly because HIV-1 can silently persist in a small reservoir of HIV-1 infected cells and when antiretroviral treatment is stopped, the virus rebounds and the immune system is depleted again. To reach an HIV-1 cure we need a better characterisation of the HIV-1 reservoir and an understanding of the mechanisms of viral persistence. We hypothesize that common persistent non-HIV viral infections (Epstein-Barr Virus and Cytomegalovirus) are a major contributing force to the persistence of the HIV-1 reservoirs. Persistent pathogens can stimulate the immune system, leading to an expansion of specific memory cells. Latent HIV-1 may reside in these cell subsets and proliferate while remaining under the radar of antiretroviral treatment. To investigate our hypothesis we will study if the HIV-1 reservoir of HIV-1 infected patients on longterm treatment is indeed mainly located in T-cells with immunological parameters against these common non-HIV pathogens. Subsequently, we will assess if the proviral DNA in these cells is clonally proliferated and if the viral sequence is non-defective. These investigations will reveal a new mechanism of viral persistence and will help future treatments to target and destroy the HIV- 1 reservoir more specifically.