Intra- and extra-cellular environments contribute to the fate of HIV-1 infection

• DOI: 10.1016/j.celrep.2021.109622
• Publication Date: 2021-08-31T15:23:49Z
• Authors: Sneha Ratnapriya; Miranda Harris; Angela Chov; Zachary T. Herbert; Vladimir Vrbanac; Maud Deruaz; Vasudevan Achuthan; Alan N. Engelman; Joseph Sodroski; Alon Herschhorn
• Keywords: CD4-Positive T-Lymphocytes; 0303 health sciences; Anti-HIV Agents; THP-1 Cells; HIV Infections; Mice, SCID; Virus Internalization; Virus Replication; Article; Virus Latency; 3. Good health; Disease Models, Animal; 03 medical and health sciences; HEK293 Cells; Cellular Microenvironment; Gene Expression Regulation; Mice, Inbred NOD; Host-Pathogen Interactions; HIV-1; Animals; Humans; Female; Transcriptome

HIV-1 entry into host cells leads to one of the following three alternative fates: (1) HIV-1 elimination by restriction factors, (2) establishment of HIV-1 latency, or (3) active viral replication in target cells. Here, we report the development of an improved system for monitoring HIV-1 fate at single-cell and population levels and show the diverse applications of this system to study specific aspects of HIV-1 fate in different cell types and under different environments. An analysis of the transcriptome of infected, primary CD4+ T cells that support alternative fates of HIV-1 identifies differential gene expression signatures in these cells. Small molecules are able to selectively target cells that support viral replication with no significant effect on viral latency. In addition, HIV-1 fate varies in different tissues following infection of humanized mice in vivo. Altogether, these studies indicate that intra- and extra-cellular environments contribute to the fate of HIV-1 infection.