TY - JOUR
T1 - CMPK2 and BCL-G are associated with type 1 interferon–induced HIV restriction in humans
AU - El-Diwany, Ramy
AU - Soliman, Mary
AU - Sugawara, Sho
AU - Breitwieser, Florian
AU - Skaist, Alyza
AU - Coggiano, Candelaria
AU - Sangal, Neel
AU - Chattergoon, Michael
AU - Bailey, Justin R.
AU - Siliciano, Robert F.
AU - Blankson, Joel N.
AU - Ray, Stuart C.
AU - Wheelan, Sarah J.
AU - Thomas, David L.
AU - Balagopal, Ashwin
N1 - Funding Information:
: We would like to thank the participants of the study for contributing these invaluable samples; D. Mohr for expertise in library preparation and optimal sequencing; H. Zhang, Z. Freeman, and R. Veenhuis for helpful discussion and assistance with designing FACS protocols; and the organizers and instructors of the Quantitative Systems Immunology Summer School at Boston University and the Computational Immunology seminar series at Johns Hopkins University for introduction to the computational methods implemented in this investigation : This work was supported by the NIH (grant nos. R37 DA013806, R01 DA016078, K08 AI102696, and R01 HG006677), U.S. Army Research Office (grant no. W911NF-14-1-0490), and the Johns Hopkins University Center for AIDS Research (P30 AI094189). This publication was made possible by the Next Generation Sequencing Center at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (P30 CA006973) and the Johns Hopkins Institute for Clinical and Translational Research (ICTR), which is funded, in part, by grant no. UL1 TR 000424-06 through a Clinical and Translational Science Award from the National Center for Advancing Translational Sciences (NCATS) (a component of the NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR, NCATS, or NIH
PY - 2018/8/1
Y1 - 2018/8/1
N2 - 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-2b (IFN-2b) injection. IFN-2b administration reduced plasma HIV RNA and induced mRNA expression in activated CD4+ T cells: The IFN-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.
AB - 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-2b (IFN-2b) injection. IFN-2b administration reduced plasma HIV RNA and induced mRNA expression in activated CD4+ T cells: The IFN-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.
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U2 - 10.1126/sciadv.aat0843
DO - 10.1126/sciadv.aat0843
M3 - Article
C2 - 30083606
AN - SCOPUS:85051397314
VL - 4
JO - Science advances
JF - Science advances
SN - 2375-2548
IS - 8
M1 - eaat0843
ER -