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

Sneha Ratnapriya, Miranda Harris, Angela Chov, Zachary T. Herbert, Vladimir Vrbanac, Maud Deruaz, Vasudevan Achuthan, Alan N. Engelman, Joseph Sodroski, Alon Herschhorn

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number109622
JournalCell reports
Volume36
Issue number9
DOIs
StatePublished - Aug 31 2021

Bibliographical note

Funding Information:
We thank Geoffrey Hart and AnyeDitJules Sangala for the help in setting up the flow cytometry experiment for testing compound effects on HIV-1 fate and analyzing the data. We thank the NIH AIDS Reagent Program for providing the pNL4-3.HSA.R-E- plasmid. A.H. is the recipient of a phase II amfAR research grant ( 109285-58-RKVA ) for independent investigators. This work was supported by the Harvard University Center for AIDS Research, National Institutes of Health grants R01AI052014 and R37AI039394 (to A.N.E.); the Humanized Immune System Mouse Program at Ragon Institute of MGH, MIT and Harvard ; and internal funds of the Department of Medicine at the University of Minnesota .

Publisher Copyright:
© 2021 The Author(s)

Keywords

  • HIV-1 fate
  • HIV-1 latency
  • humanized mouse model
  • transcriptomic analysis

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