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

doi:10.1016/j.celrep.2021.109622

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 journal › Article › peer-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 language	English (US)
Article number	109622
Journal	Cell reports
Volume	36
Issue number	9
DOIs	https://doi.org/10.1016/j.celrep.2021.109622
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2021.109622

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title = "Intra- and extra-cellular environments contribute to the fate of HIV-1 infection",

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.",

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AU - Deruaz, Maud

AU - Achuthan, Vasudevan

AU - Engelman, Alan N.

AU - Sodroski, Joseph

AU - Herschhorn, Alon

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N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

Keywords

UN SDGs

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