HIV-1 Activation of Innate Immunity Depends Strongly on the Intracellular Level of TREX1 and Sensing of Incomplete Reverse Transcription Products.

Journal of Virology
Swati KumarEric Poeschla

Abstract

TREX1 has been reported to degrade cytosolic immune-stimulatory DNA, including viral DNA generated during HIV-1 infection; but the dynamic range of its capacity to suppress innate immune stimulation is unknown, and its full role in the viral life cycle remains unclear. A main purpose of our study was to determine how the intracellular level of TREX1 affects HIV-1 activation and avoidance of innate immunity. Using stable overexpression and CRISPR-mediated gene disruption, we engineered a range of TREX1 levels in human THP-1 monocytes. Increasing the level of TREX1 dramatically suppressed HIV-1 induction of interferon-stimulated genes (ISGs). Productive infection and integrated proviruses were equal or increased. Knocking out TREX1 impaired viral infectivity, increased early viral cDNA, and caused 10-fold or greater increases in HIV-1 ISG induction. Knockout of cyclic GMP-AMP synthase (cGAS) abrogated all ISG induction. Moreover, cGAS knockout produced no increase in single-cycle infection, establishing that HIV-1 DNA-triggered signaling is not rapid enough to impair the initial ISG-triggering infection cycle. Disruption of the HIV-1 capsid by PF74 also induced ISGs, and this was TREX1 level dependent, required reverse transcript...Continue Reading

References

Jul 3, 1999·The Journal of Biological Chemistry·D J Mazur, F W Perrino
Mar 30, 2001·The Journal of Biological Chemistry·D J Mazur, F W Perrino
Sep 9, 2006·Science·Manuel LlanoEric M Poeschla
Aug 30, 2008·Cell·Daniel B StetsonRuslan Medzhitov
Sep 23, 2008·The Journal of Biological Chemistry·Duane A LehtinenFred W Perrino
Jan 6, 2009·Immunological Reviews·Osamu Takeuchi, Shizuo Akira
Apr 23, 2011·Nature·Thomas PertelJeremy Luban
Jun 2, 2011·Proceedings of the National Academy of Sciences of the United States of America·Amy E HulmeThomas J Hope
Aug 3, 2011·The Journal of Biological Chemistry·Jason M FyeFred W Perrino
Oct 3, 2012·Cold Spring Harbor Perspectives in Medicine·Wei-Shau Hu, Stephen H Hughes
Oct 19, 2012·Journal of Virology·Yang YangFelipe Diaz-Griffero
May 15, 2013·Proceedings of the National Academy of Sciences of the United States of America·Spyridon StavrouSusan R Ross
Oct 26, 2013·Nature Protocols·F Ann RanFeng Zhang
May 13, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andrea AblasserVeit Hornung
May 13, 2014·Frontiers in Microbiology·Maroof Hasan, Nan Yan
Jan 27, 2015·Current Opinion in Immunology·Aymeric Silvin, Nicolas Manel
Mar 31, 2015·Cell Host & Microbe·Spyridon StavrouSusan R Ross
Aug 1, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Elizabeth E GrayDaniel B Stetson
Apr 15, 2016·Journal of Virology·Akatsuki SaitoMasahiro Yamashita

❮ Previous
Next ❯

Citations

Jul 13, 2018·AIDS Research and Human Retroviruses·Sho SugawaraAshwin Balagopal
Feb 19, 2019·Clinical and Experimental Immunology·M T Boswell, S L Rowland-Jones
Jun 7, 2019·Journal of Virology·Mohammad Adnan SiddiquiMasahiro Yamashita
Feb 14, 2020·Journal of Virology·Caitlin M MillerEric M Poeschla
Apr 12, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laura BankersEric M Poeschla
Jul 28, 2020·Proceedings of the National Academy of Sciences of the United States of America·Carina ElsnerChristine Goffinet
Aug 6, 2020·Viruses·Eileen A Moran, Susan R Ross
Jan 24, 2020·Cells·Xin YinSumit K Chanda
Dec 22, 2020·Frontiers in Microbiology·Pavitra RamdasAjit Chande
Jul 3, 2020·DNA Repair·Sean R SimpsonFred W Perrino
May 11, 2021·The FEBS Journal·Boris RyabchenkoSandra Huérfano

❮ Previous
Next ❯

Related Concepts

Related Feeds

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.

CRISPR Ribonucleases Deactivation

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on mechanisms that underlie deactivation of CRISPR ribonucleases. Here is the latest research.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Virology & CRISPR

This feed focuses on the virology of CRISPR and its use in developing CRISPR-Cas systems. Discover the latest research here.