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

被引：52

作者：

El-Diwany, Ramy ^{[1
,2
]}

Soliman, Mary ^{[1
]}

Sugawara, Sho ^{[1
]}

Breitwieser, Florian ^{[3
]}

Skaist, Alyza ^{[4
]}

Coggiano, Candelaria ^{[1
]}

Sangal, Neel ^{[1
]}

Chattergoon, Michael ^{[1
]}

Bailey, Justin R. ^{[1
]}

Siliciano, Robert F. ^{[1
,2
,5
]}

Blankson, Joel N. ^{[1
]}

Ray, Stuart C. ^{[1
]}

Wheelan, Sarah J. ^{[4
]}

Thomas, David L. ^{[1
]}

Balagopal, Ashwin ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Ctr Computat Biol, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA

[5] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA

来源：

SCIENCE ADVANCES | 2018年 / 4卷 / 08期

关键词：

CD4(+) T-LYMPHOCYTES; IN-VIVO; INFECTION; DYNAMICS; ALPHA-2A; CELLS; ENTRY; RNA; REPLICATION; SUPPRESSION;

D O I：

10.1126/sciadv.aat0843

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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-alpha 2b (IFN-alpha 2b) injection. IFN-alpha 2b administration reduced plasma HIV RNA and induced mRNA expression in activated CD4(+) T cells: The IFN-alpha 2b-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.

引用

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