PMID- 37209263 OWN - NLM STAT- MEDLINE DCOM- 20230811 LR - 20230815 IS - 1559-1182 (Electronic) IS - 0893-7648 (Print) IS - 0893-7648 (Linking) VI - 60 IP - 9 DP - 2023 Sep TI - Occludin Regulates HIV-1 Infection by Modulation of the Interferon Stimulated OAS Gene Family. PG - 4966-4982 LID - 10.1007/s12035-023-03381-0 [doi] AB - HIV-1-associated blood brain barrier (BBB) alterations and neurocognitive disorders are frequent clinical manifestations in HIV-1 infected patients. The BBB is formed by cells of the neurovascular unit (NVU) and sealed together by tight junction proteins, such as occludin (ocln). Pericytes are a key cell type of NVU that can harbor HIV-1 infection via a mechanism that is regulated, at least in part, by ocln. After viral infection, the immune system starts the production of interferons, which induce the expression of the 2'-5'-oligoadenylate synthetase (OAS) family of interferon stimulated genes and activate the endoribonuclease RNaseL that provides antiviral protection by viral RNA degradation. The current study evaluated the involvement of the OAS genes in HIV-1 infection of cells of NVU and the role of ocln in controlling OAS antiviral signaling pathway. We identified that ocln modulates the expression levels of the OAS1, OAS2, OAS3, and OASL genes and proteins and, in turn, that the members of the OAS family can influence HIV replication in human brain pericytes. Mechanistically, this effect was regulated via the STAT signaling. HIV-1 infection of pericytes significantly upregulated expression of all OAS genes at the mRNA level but selectively OAS1, OAS2, and OAS3 at the protein level. Interestingly no changes were found in RNaseL after HIV-1 infection. Overall, these results contribute to a better understanding of the molecular mechanisms implicated in the regulation of HIV-1 infection in human brain pericytes and suggest a novel role for ocln in controlling of this process. CI - (c) 2023. The Author(s). FAU - Torices, Silvia AU - Torices S AD - Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 11336, USA. storicesval@gmail.com. FAU - Teglas, Timea AU - Teglas T AD - Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 11336, USA. FAU - Naranjo, Oandy AU - Naranjo O AD - Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 11336, USA. FAU - Fattakhov, Nikolai AU - Fattakhov N AD - Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 11336, USA. FAU - Frydlova, Kristyna AU - Frydlova K AD - Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 11336, USA. FAU - Cabrera, Rosalba AU - Cabrera R AD - Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 11336, USA. FAU - Osborne, Olivia M AU - Osborne OM AD - Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 11336, USA. FAU - Sun, Enze AU - Sun E AD - Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 11336, USA. FAU - Kluttz, Allan AU - Kluttz A AD - Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 11336, USA. FAU - Toborek, Michal AU - Toborek M AUID- ORCID: 0000-0003-4475-2119 AD - Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 11336, USA. mtoborek@med.miami.edu. LA - eng GR - NS125905/NS/NINDS NIH HHS/United States GR - R01 MH128022/MH/NIMH NIH HHS/United States GR - R01 DA044579/DA/NIDA NIH HHS/United States GR - DA050528, DA044579, DA050528-02S1/DA/NIDA NIH HHS/United States GR - R21 MH122235/MH/NIMH NIH HHS/United States GR - R01 HL126559/HL/NHLBI NIH HHS/United States GR - F31 NS125905/NS/NINDS NIH HHS/United States GR - R01 DA050528/DA/NIDA NIH HHS/United States GR - MH128022, MH072567, MH122235/MH/NIMH NIH HHS/United States GR - HL126559/HL/NHLBI NIH HHS/United States GR - R01 MH072567/MH/NIMH NIH HHS/United States PT - Journal Article DEP - 20230520 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 9008-11-1 (Interferons) RN - 0 (Occludin) RN - EC 2.7.7.84 (2',5'-Oligoadenylate Synthetase) RN - 0 (Antiviral Agents) SB - IM UOF - Res Sq. 2023 Jan 30;:. PMID: 36778388 MH - Humans MH - Interferons MH - Occludin/genetics MH - *HIV-1/metabolism MH - 2',5'-Oligoadenylate Synthetase/genetics MH - *HIV Infections/genetics MH - Antiviral Agents PMC - PMC10199280 OTO - NOTNLM OT - Blood brain barrier OT - HIV-1 OT - Interferon OT - OAS OT - Occludin OT - Pericytes OT - RNaseL COIS- The authors declare no competing interests. EDAT- 2023/05/20 19:13 MHDA- 2023/08/11 06:43 PMCR- 2023/05/20 CRDT- 2023/05/20 14:56 PHST- 2023/01/25 00:00 [received] PHST- 2023/05/04 00:00 [accepted] PHST- 2023/08/11 06:43 [medline] PHST- 2023/05/20 19:13 [pubmed] PHST- 2023/05/20 14:56 [entrez] PHST- 2023/05/20 00:00 [pmc-release] AID - 10.1007/s12035-023-03381-0 [pii] AID - 3381 [pii] AID - 10.1007/s12035-023-03381-0 [doi] PST - ppublish SO - Mol Neurobiol. 2023 Sep;60(9):4966-4982. doi: 10.1007/s12035-023-03381-0. Epub 2023 May 20.