PMID- 25769457 OWN - NLM STAT- MEDLINE DCOM- 20160426 LR - 20201209 IS - 1931-8405 (Electronic) IS - 0889-2229 (Print) IS - 0889-2229 (Linking) VI - 31 IP - 8 DP - 2015 Aug TI - Non-POU Domain-Containing Octamer-Binding Protein Negatively Regulates HIV-1 Infection in CD4(+) T Cells. PG - 806-16 LID - 10.1089/AID.2014.0313 [doi] AB - HIV-1 interacts with numerous cellular proteins during viral replication. Identifying such host proteins and characterizing their roles in HIV-1 infection can deepen our understanding of the dynamic interplay between host and pathogen. We previously identified non-POU domain-containing octamer-binding protein (NonO or p54nrb) as one of host factors associated with catalytically active preintegration complexes (PIC) of HIV-1 in infected CD4(+) T cells. NonO is involved in nuclear processes including transcriptional regulation and RNA splicing. Although NonO has been identified as an HIV-1 interactant in several recent studies, its role in HIV-1 replication has not been characterized. We investigated the effect of NonO on the HIV-1 life cycle in CD4(+) T cell lines and primary CD4(+) T cells using single-cycle and replication-competent HIV-1 infection assays. We observed that short hairpin RNA (shRNA)-mediated stable NonO knockdown in a CD4(+) Jurkat T cell line and primary CD4(+) T cells did not affect cell viability or proliferation, but enhanced HIV-1 infection. The enhancement of HIV-1 infection in Jurkat T cells correlated with increased viral reverse transcription and gene expression. Knockdown of NonO expression in Jurkat T cells modestly enhanced HIV-1 gag mRNA expression and Gag protein synthesis, suggesting that viral gene expression and RNA regulation are the predominantly affected events causing enhanced HIV-1 replication in NonO knockdown (KD) cells. Furthermore, overexpression of NonO in Jurkat T cells reduced HIV-1 single-cycle infection by 41% compared to control cells. Our data suggest that NonO negatively regulates HIV-1 infection in CD4(+) T cells, albeit it has modest effects on early and late stages of the viral life cycle, highlighting the importance of host proteins associated with HIV-1 PIC in regulating viral replication. FAU - St Gelais, Corine AU - St Gelais C AD - 1 Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University , Columbus, Ohio. FAU - Roger, Jonathan AU - Roger J AD - 1 Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University , Columbus, Ohio. FAU - Wu, Li AU - Wu L AD - 1 Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University , Columbus, Ohio. AD - 2 Department of Microbial Infection and Immunity, The Ohio State University , Columbus, Ohio. AD - 3 Comprehensive Cancer Center, The Ohio State University , Columbus, Ohio. LA - eng GR - R01 AI104483/AI/NIAID NIH HHS/United States GR - R21 AI102822/AI/NIAID NIH HHS/United States GR - AI102822/AI/NIAID NIH HHS/United States GR - AI104483/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150406 PL - United States TA - AIDS Res Hum Retroviruses JT - AIDS research and human retroviruses JID - 8709376 RN - 0 (DNA-Binding Proteins) RN - 0 (NONO protein, human) RN - 0 (Nuclear Matrix-Associated Proteins) RN - 0 (Octamer Transcription Factors) RN - 0 (RNA-Binding Proteins) SB - IM MH - CD4-Positive T-Lymphocytes/*immunology/*virology MH - Cells, Cultured MH - DNA-Binding Proteins MH - Gene Knockdown Techniques MH - HIV-1/*immunology/*physiology MH - *Host-Pathogen Interactions MH - Humans MH - Nuclear Matrix-Associated Proteins/antagonists & inhibitors/*metabolism MH - Octamer Transcription Factors/antagonists & inhibitors/*metabolism MH - RNA-Binding Proteins/antagonists & inhibitors/*metabolism MH - *Virus Replication PMC - PMC4533096 EDAT- 2015/03/15 06:00 MHDA- 2016/04/27 06:00 PMCR- 2016/08/01 CRDT- 2015/03/15 06:00 PHST- 2015/03/15 06:00 [entrez] PHST- 2015/03/15 06:00 [pubmed] PHST- 2016/04/27 06:00 [medline] PHST- 2016/08/01 00:00 [pmc-release] AID - 10.1089/aid.2014.0313 [pii] AID - 10.1089/AID.2014.0313 [doi] PST - ppublish SO - AIDS Res Hum Retroviruses. 2015 Aug;31(8):806-16. doi: 10.1089/AID.2014.0313. Epub 2015 Apr 6.