Importance of STING signaling in the modulation of regulatory T lymphocytes by HSV-1 in vivo

• Grant number: 25/21300-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: February 01, 2026
• End date: January 31, 2027
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: José Carlos Farias Alves Filho
• Grantee: Fernando Yutaka de Ferreira
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

Herpes Simplex Virus type 1 (HSV-1) is a double-stranded DNA pathogen that initiates infection in keratinocytes of the skin, mucosa, or genitals, where it replicates extensively, leading to cell lysis and vesicular lesion formation. Subsequently, the virus migrates to sensory ganglia, establishing latent infection. The immune response to HSV-1 relies on a delicate balance between antiviral mechanisms and the control of immunopathology, in which regulatory T cells (Tregs) play a central role. The absence of Tregs, although favoring viral clearance, exacerbates tissue damage due to an uncontrolled inflammatory response. Conversely, excessive suppression mediated by Tregs may impair viral elimination and contribute to latency and persistence of the pathogen. Within the innate immune response, recognition of cytoplasmic viral DNA occurs through the cGAS/STING pathway, which is essential for interferon production and the initial inflammatory response. Although evidence indicates that HSV-1 activates this pathway, its impact on Treg functionality remains poorly understood. Therefore, this project aims to investigate the immunomodulatory effects of HSV-1 on Tregs mediated by STING activation in vivo. To this end, we will employ a murine model with conditional deletion of STING in Tregs, subjected to cutaneous HSV-1 infection. Elucidating these mechanisms may reveal potential therapeutic targets to prevent viral persistence and reactivation. (AU)