Virus Expression Database
Submitted by Daekwan Seo (Yonsei University College of Medicine, South Korea) on Jun 12 2014
Platform: ngs – Illumina HiSeq 2500 (Homo sapiens)
Pubmed: 25038827
Summary SAMHD1 restricts HIV-1 replication in dendritic and other myeloid cells. SAMHD1 has been shown to possess a dGTP-dependent dNTP triphosphatase (dNTPase) activity and is proposed to inhibit HIV-1 replication by depleting the intracellular dNTP pool. Arguing against a role for SAMHD1 dNTPase in HIV-1 restriction, the phosphorylation of SAMHD1 regulates the restriction activity toward HIV-1 without affecting its ability to decrease cellular dNTP levels. Here, we show that SAMHD1 is a phospho-regulated RNase and that the RNase function is required for HIV-1 restriction. Mutation of the SAMHD1 D137 residue in the allosteric site (SAMHD1D137N) abolishes dNTPase activity but has no effect on RNase activity. This dNTPase-defective SAMHD1D137N mutant is able to restrict HIV-1 infection to nearly the same extent as wild-type SAMHD1. SAMHD1 associates with and degrades the HIV-1 genomic RNA during the early phases of infection. SAMHD1 silencing in macrophages and CD4+ T cells from healthy donors increases HIV-1 RNA stability, thus rendering the cells permissive for HIV-1 infection. Furthermore, the phosphorylation of SAMHD1 at position T592 abolishes the RNase activity toward HIV-1 RNA, and consequently the ability of SAMHD1 to restrict HIV-1 infection, uncovering the phosphorylation of SAMHD1 T592 as a negative regulatory mechanism of RNase activity. Together, our results demonstrate that SAMHD1 is an essential RNase that prevents HIV-1 infection by directly degrading HIV-1 genomic RNA in a phosphorylation-regulated manner. The unique property of SAMHD1 that cleaves HIV-1 genomic RNA with no sequence preferences could be exploited to develop a new class of intervention for error-prone retroviruses.
| ID | Title | Cell Type | Timepoint | Reported Virus | Virus Species | Exclusion Reason |
|---|---|---|---|---|---|---|
| GSM1410581 | U937, Mock 0h | promonocytic leukemia cell line  [U-937  ] |
mock | Uninfected | ||
| GSM1410582 | U937, Mock 1h | promonocytic leukemia cell line [U-937 ] |
1 hr | mock | Uninfected | |
| GSM1410583 | U937, Mock 3h | promonocytic leukemia cell line [U-937 ] |
3 hrs | mock | Uninfected | |
| GSM1410584 | U937, WT 0h | promonocytic leukemia cell line [U-937 ] |
HIV-1 | Uninfected | Data failed QCpct_pseudoaligned is 17.9% (low fraction of usable reads) |
|
| GSM1410585 | U937, WT 1h | promonocytic leukemia cell line [U-937 ] |
1 hr | HIV-1 | Human immunodeficiency virus 1 | |
| GSM1410586 | U937, WT 3h | promonocytic leukemia cell line [U-937 ] |
3 hrs | HIV-1 | Human immunodeficiency virus 1 | Data failed QCpct_pseudoaligned is 13.2% (low fraction of usable reads) |
| GSM1410587 | U937, D207N 0h | promonocytic leukemia cell line [U-937 ] |
HIV-1 | Human immunodeficiency virus 1 | Extra interventions mutant SAMHD1 (D207N) |
|
| GSM1410588 | U937, D207N 1h | promonocytic leukemia cell line [U-937 ] |
1 hr | HIV-1 | Human immunodeficiency virus 1 | Extra interventions mutant SAMHD1 (D207N) |
| GSM1410589 | U937, D207N 3h | promonocytic leukemia cell line [U-937 ] |
3 hrs | HIV-1 | Human immunodeficiency virus 1 | Extra interventions mutant SAMHD1 (D207N) |
| GSM1410590 | U937, D137N 0h | promonocytic leukemia cell line [U-937 ] |
HIV-1 | Human immunodeficiency virus 1 | Extra interventions mutant SAMHD1 (D137N) |
|
| GSM1410591 | U937, D137N 1h | promonocytic leukemia cell line [U-937 ] |
1 hr | HIV-1 | Human immunodeficiency virus 1 | Extra interventions mutant SAMHD1 (D137N) |
| GSM1410592 | U937, D137N 3h | promonocytic leukemia cell line [U-937 ] |
3 hrs | HIV-1 | Human immunodeficiency virus 1 | Extra interventions mutant SAMHD1 (D137N) |