CMPK2 and BCL-G are associated with type 1 interferon-induced HIV restriction in humans

Ramy El-Diwany; Mary Soliman; Sho Sugawara; Florian Breitwieser; Alyza Skaist; Candelaria Coggiano; Neel Sangal; Michael Chattergoon; Justin R Bailey; Robert F Siliciano; Joel N Blankson; Stuart C Ray; Sarah J Wheelan; David L Thomas; Ashwin Balagopal

doi:10.1126/sciadv.aat0843

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CMPK2 and BCL-G are associated with type 1 interferon-induced HIV restriction in humans

Journal article

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CMPK2 and BCL-G are associated with type 1 interferon-induced HIV restriction in humans

Ramy El-Diwany, Mary Soliman, Sho Sugawara, Florian Breitwieser, Alyza Skaist, Candelaria Coggiano, Neel Sangal, Michael Chattergoon, Justin R Bailey, Robert F Siliciano, …

Science advances, Vol.4(8), p.eaat0843

08/01/2018

DOI: 10.1126/sciadv.aat0843

PMCID: PMC6070316

PMID: 30083606

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Abstract

Type 1 interferons (IFN) are critical for host control of HIV and simian immunodeficiency virus. However, it is unknown which of the hundreds of interferon-stimulated genes (ISGs) restrict HIV in vivo. We sequenced RNA from cells that support HIV replication (activated CD4 T cells) in 19 HIV-infected people before and after interferon-α2b (IFN-α2b) injection. IFN-α2b administration reduced plasma HIV RNA and induced mRNA expression in activated CD4 T cells: The IFN-α2b-induced change of each mRNA was compared to the change in plasma HIV RNA. Of 99 ISGs, 13 were associated in magnitude with plasma HIV RNA decline. In addition to well-known restriction factors among the 13 ISGs, two novel genes, CMPK2 and BCL-G, were identified and confirmed for their ability to restrict HIV in vitro: The effect of IFN on HIV restriction in culture was attenuated with RNA interference to CMPK2, and overexpression of BCL-G diminished HIV replication. These studies reveal novel antiviral molecules that are linked with IFN-mediated restriction of HIV in humans.

Antiviral Agents - pharmacology

CD4-Positive T-Lymphocytes - drug effects

CD4-Positive T-Lymphocytes - immunology

Gene Expression Regulation

HIV - drug effects

HIV Infections - drug therapy

HIV Infections - immunology

HIV Infections - metabolism

Humans

Interferon alpha-2

Interferon Regulatory Factors - genetics

Interferon Regulatory Factors - metabolism

Interferon-alpha - pharmacology

Prospective Studies

Proto-Oncogene Proteins c-bcl-2 - genetics

Proto-Oncogene Proteins c-bcl-2 - metabolism

Virus Replication - drug effects

Details

Title: Subtitle: CMPK2 and BCL-G are associated with type 1 interferon-induced HIV restriction in humans
Creators: Ramy El-Diwany - Johns Hopkins University School of Medicine
Mary Soliman - Johns Hopkins Medicine
Sho Sugawara - Johns Hopkins Medicine
Florian Breitwieser - Johns Hopkins Medicine
Alyza Skaist - Johns Hopkins University
Candelaria Coggiano - Johns Hopkins Medicine
Neel Sangal - Johns Hopkins Medicine
Michael Chattergoon - Johns Hopkins Medicine
Justin R Bailey - Johns Hopkins University
Robert F Siliciano - Johns Hopkins Medicine
Joel N Blankson - Johns Hopkins Medicine
Stuart C Ray - Johns Hopkins University
Sarah J Wheelan - Johns Hopkins Medicine
David L Thomas - Johns Hopkins Medicine
Ashwin Balagopal - Johns Hopkins Medicine
Resource Type: Journal article
Publication Details: Science advances, Vol.4(8), p.eaat0843
DOI: 10.1126/sciadv.aat0843
PMID: 30083606
PMCID: PMC6070316
NLM abbreviation: Sci Adv
ISSN: 2375-2548
eISSN: 2375-2548
Grant note: R01 AI116868 / NIAID NIH HHS P30 CA006973 / NCI NIH HHS R01 HG006677 / NHGRI NIH HHS R01 DA016078 / NIDA NIH HHS UL1 TR000424 / NCATS NIH HHS T32 GM008752 / NIGMS NIH HHS K08 AI102696 / NIAID NIH HHS R37 DA013806 / NIDA NIH HHS R01 DA013806 / NIDA NIH HHS P30 AI094189 / NIAID NIH HHS
Language: English
Date published: 08/01/2018
Academic Unit: Surgery
Record Identifier: 9984966747802771

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