Abstract
AbstractHIV-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.
Funder
National Heart, Lung, and Blood Institute
National Institute of Mental Health
National Institute on Drug Abuse
National Institute of Neurological Disorders and Stroke
National Institute of Allergy and Infectious Diseases
Publisher
Springer Science and Business Media LLC
Subject
Neuroscience (miscellaneous),Cellular and Molecular Neuroscience,Neurology
Cited by
2 articles.
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1. Targeting HIV persistence in the tissue;Current Opinion in HIV and AIDS;2023-12-14
2. Occludin: a gatekeeper of brain Infection by HIV-1;Fluids and Barriers of the CNS;2023-10-16