Review links OAS1 regulation to HIV restriction and persistence

A 2026 review identifies 2′-5′-oligoadenylate synthetase 1 (OAS1) as a multifunctional component of host defence against HIV-1, linking its established antiviral role with possible effects on viral persistence, immune regulation, neuroinflammation and retroviral disease progression. The paper surveys the broader 2′-5′-oligoadenylate synthetase protein family but focuses on OAS1, an interferon-stimulated gene that senses viral double-stranded RNA and activates the OAS–RNase L pathway. Its scope is a synthesis of experimental and clinical evidence rather than a new experiment or clinical trial.

OAS1 acts within the innate immune mechanisms that can restrict HIV despite the virus’s ability to establish persistent infection during effective antiretroviral therapy. The review examines the genomic organization, structural diversity, isoform-specific functions, genetic variation and interferon-mediated regulation of OAS proteins. Alternative splicing and polymorphisms create functional diversity within OAS1 and may influence antiviral activity, individual susceptibility and clinical outcomes.

The evidence therefore should not be read as showing that every OAS1 variant has the same effect on viral replication or disease. Experimental and clinical studies summarized by the review report that type I and type III interferons induce OAS1 in macrophages, dendritic cells, epithelial and endothelial cells, microglia and lymphocytes. In this setting, OAS1 contributes to HIV restriction through RNase L activation and enhanced innate antiviral responses.

OAS signalling may also support antiviral defence at mucosal surfaces, influence viral burden and chronic immune activation, and affect interferon responsiveness during combination antiretroviral therapy. These are biological associations and potential roles in host defence, not evidence that activating OAS1 has demonstrated clinical benefit in people living with HIV. The review also examines the more complex relationship between OAS1, the central nervous system and HIV pathogenesis.

OAS signalling has been associated with central nervous system protection, whereas dysregulated OAS1 expression has been associated with HIV-associated neurocognitive disorders. The available evidence does not support a simple model in which increased OAS1 expression is uniformly beneficial: the review presents antiviral activity and abnormal regulation in a context-dependent framework. Its conclusions are constrained by the varied experimental systems, cellular responses, isoforms and genetic backgrounds represented across the studies it considers.

For viral scientists, the review positions OAS1 as both a restriction factor and a potential immunoregulatory node in persistent retroviral infection. It identifies investigation of OAS1 activation, genetic variation, isoform-specific functions and immune modulation as avenues that may facilitate biomarker discovery and the development of host-directed strategies against persistent retroviral infections. Its principal contribution is to organize current evidence on how this double-stranded-RNA sensor fits into interferon-driven immunity and may connect HIV replication, persistence, tissue-specific immune responses and disease-related inflammation.

Subject of Research: OAS1-mediated innate antiviral and immunoregulatory responses in HIV-1 infection

Article Title: The role of 2’-5’-oligoadenylate synthetase (OAS) proteins in HIV infection: innate antiviral immunity, viral persistence, and therapeutic opportunities

Article References: Akbarin, M. M., Farjami, Z., Soltani, M., & Álvarez, H. R. (2026). The role of 2’-5’-oligoadenylate synthetase (OAS) proteins in HIV infection: innate antiviral immunity, viral persistence, and therapeutic opportunities. Molecular Biology Reports, 53(1), Article 1781. https://doi.org/10.1007/s11033-026-13013-0

Image Credits: AI Generated

DOI: 10.1007/s11033-026-13013-0

Keywords: HIV-1, OAS1, innate immunity, RNase L, interferon, viral persistence, neuroinflammation, genetic variation, role, oligoadenylate, synthetase, proteins