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Occludin Regulates HIV-1 Infection by Modulation of the Interferon Stimulated OAS Gene Family.
Torices, Silvia; Teglas, Timea; Naranjo, Oandy; Fattakhov, Nikolai; Frydlova, Kristyna; Cabrera, Rosalba; Osborne, Olivia M; Sun, Enze; Kluttz, Allan; Toborek, Michal.
Afiliación
  • Torices S; 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.
  • Teglas T; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 11336, USA.
  • Naranjo O; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 11336, USA.
  • Fattakhov N; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 11336, USA.
  • Frydlova K; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 11336, USA.
  • Cabrera R; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 11336, USA.
  • Osborne OM; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 11336, USA.
  • Sun E; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 11336, USA.
  • Kluttz A; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 11336, USA.
  • Toborek M; 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.
Mol Neurobiol ; 60(9): 4966-4982, 2023 Sep.
Article en En | MEDLINE | ID: mdl-37209263
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por VIH / VIH-1 Límite: Humans Idioma: En Revista: Mol Neurobiol Asunto de la revista: BIOLOGIA MOLECULAR / NEUROLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por VIH / VIH-1 Límite: Humans Idioma: En Revista: Mol Neurobiol Asunto de la revista: BIOLOGIA MOLECULAR / NEUROLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos