Generation and evaluation of an EcoHIV mouse model to study HIV-1 integration and expression.

Antiretroviral therapy suppresses HIV replication but does not purge the latent reservoirs, which remains a major barrier to cure. There is an urgent need to establish a reservoir in a mouse model for investigation of viral replication and clearance. We established an EcoHIV infection model in conventional mice by replacing HIV-1 gp120 protein with an ecotropic murine leukemia virus envelope to enable entry via the murine mCAT-1 receptor. EcoHIV can infect immunocompetent mice and multiple mutant mouse strains and replicate in CD4+ T cells, macrophages, and immune cells in the brain. We created and systematically validated a nested qPCR for quantitation of HIV-1/EcoHIV integration events, and we found that viral genomic integration was significantly suppressed by HIV-1 integrase inhibitors such as Raltegravir. The immunofluorescence staining indicated EcoHIV can be efficiently transmitted from infected CD4 + T cells to macrophages in vitro and EcoHIV expression was effectively inhibited by Abacavir and Raltegravir. Importantly, BLI data demonstrate that EcoHIV establishes latent reservoirs -like state in mice which can be reactivated by LRA treatment. Altogether, our model provides a valuable platform for the controlled study of HIV entry, integration, transmission, latency within tissue-resident compartments under ART and for the preclinical evaluation of latency-reversing and curative strategies.