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-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.
| Language | English (US) |
|---|---|
| Article number | eaat0843 |
| Journal | Science advances |
| Volume | 4 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 1 2018 |
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CMPK2 and BCL-G are associated with type 1 interferon–induced HIV restriction in humans. / El-Diwany, Ramy; Soliman, Mary; Sugawara, Sho; Breitwieser, Florian; Skaist, Alyza; Coggiano, Candelaria; Sangal, Neel; Chattergoon, Michael Anand; Bailey, Justin; Siliciano, Robert F; Blankson, Joel N; Ray, Stuart Campbell; Wheelan, Sarah; Thomas, David L; Balagopal, Ashwin.
In: Science advances, Vol. 4, No. 8, eaat0843, 01.08.2018.Research output: Contribution to journal › Article
}
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 Anand
AU - Bailey, Justin
AU - Siliciano, Robert F
AU - Blankson, Joel N
AU - Ray, Stuart Campbell
AU - Wheelan, Sarah
AU - Thomas, David L
AU - Balagopal, Ashwin
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.
UR - http://www.scopus.com/inward/record.url?scp=85051397314&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85051397314&partnerID=8YFLogxK
U2 - 10.1126/sciadv.aat0843
DO - 10.1126/sciadv.aat0843
M3 - Article
VL - 4
JO - Science advances
T2 - Science advances
JF - Science advances
SN - 2375-2548
IS - 8
M1 - eaat0843
ER -