HIV latency endures as a major hurdle in disease eradication.
Combination antiretroviral therapy (cART) is extremely effective at suppressing HIV infection and replication, but has a negligible effect at eliminating long-lived immune cells infected with a dormant provirus. These cells are termed latently infected because dormant viruses can be reactivated in periods of cellular stress or when a patient ceases cART. Latently infected cells thereby constitute one of the most formidable obstacles to finding a cure for HIV. Several cellular mechanisms have been identified that can partially explain how some cells become latently infected, but the complete scheme of latency-inducing factors has not yet been extensively defined. One of the lab's research topics is to investigate how the host’s own immune system may indirectly contribute to the creation of a subset of latently infected cells.
Possible Role of APOBEC3 in HIV latency
APOBEC3 (A3) proteins are expressed in host immune cells targeted by HIV and normally constitute an important barrier to retrovirus infection. They do so by inducing intense and inactivating mutations in HIV DNA. However, low levels of mutations may in some instances help the virus evade immune detection. Our research has revealed that certain members of the APOBEC3 (A3) family of host-encoded HIV restriction factors can in some instances help the virus evolve by sublethally mutating HIV-1 proviral DNA. Importantly, we find that A3 proteins target the HIV-1 long terminal repeat (LTR) promoter, notably on transcription factor binding sites and other regulatory regions.
As such, we hypothesize that A3 proteins partake in generating sublethally mutated HIV-1 virions that display a latency-prone phenotype that contributes to the latent infected cell reservoir.