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

Medicine - Infectious Disease and International

Research output: Contribution to journal › Article › peer-review

10 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)

Access

10.1016/j.celrep.2021.109622

OpenUrl availability

Full text

Cite this

@article{6ddaed710409407e90351c9154099eb7,

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.",

keywords = "HIV-1 fate, HIV-1 latency, humanized mouse model, transcriptomic analysis",

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

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: {\textcopyright} 2021 The Author(s)",

year = "2021",

month = aug,

day = "31",

doi = "10.1016/j.celrep.2021.109622",

language = "English (US)",

volume = "36",

journal = "Cell reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "9",

}

TY - JOUR

T1 - Intra- and extra-cellular environments contribute to the fate of HIV-1 infection

AU - Ratnapriya, Sneha

AU - Harris, Miranda

AU - Chov, Angela

AU - Herbert, Zachary T.

AU - Vrbanac, Vladimir

AU - Deruaz, Maud

AU - Achuthan, Vasudevan

AU - Engelman, Alan N.

AU - Sodroski, Joseph

AU - Herschhorn, Alon

N1 - 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)

PY - 2021/8/31

Y1 - 2021/8/31

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.

KW - HIV-1 fate

KW - HIV-1 latency

KW - humanized mouse model

KW - transcriptomic analysis

UR - http://www.scopus.com/inward/record.url?scp=85113927028&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85113927028&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2021.109622

DO - 10.1016/j.celrep.2021.109622

M3 - Article

C2 - 34469717

AN - SCOPUS:85113927028

SN - 2211-1247

VL - 36

JO - Cell reports

JF - Cell reports

IS - 9

M1 - 109622

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this