{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T20:14:13Z","timestamp":1789503253808,"version":"build-2803163510"},"reference-count":88,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004001","name":"Science and Technology Foundation of Guizhou Province","doi-asserted-by":"crossref","award":["QKHJ-ZK [2023]560"],"award-info":[{"award-number":["QKHJ-ZK [2023]560"]}],"id":[{"id":"10.13039\/501100004001","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Young Talent Training Project of the Science and Technology Bureau of Zunyi City","award":["ZSKHHZ-[2023]198"],"award-info":[{"award-number":["ZSKHHZ-[2023]198"]}]},{"name":"Project of the Science and Technology Bureau of Zunyi City","award":["ZSKHHZ-[2024]201"],"award-info":[{"award-number":["ZSKHHZ-[2024]201"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Herpes simplex virus type 2 (HSV-2) is the primary pathogen responsible for genital herpes. Predominantly transmitted via sexual contact, HSV-2 not only poses significant physical and psychological burdens on infected individuals but also substantially elevates the risk of HIV acquisition and represents a potentially fatal threat to newborns. Following primary infection, HSV-2 establishes lifelong latent infection within the sacral ganglia. Currently, there are no vaccines or therapeutics capable of eradicating this latent virus reservoir or effectively preventing initial infection. The core impediment to developing such interventions lies in the incomplete elucidation of the protective immune mechanisms against HSV-2 and its precise molecular pathogenesis. The host immune response against HSV-2 hinges critically on the coordinated interplay between innate and adaptive immunity. The innate immune system, serving as the first line of defense, acts to curtail early viral replication and initiate adaptive responses. This is achieved through mechanisms, including the genital mucosal barrier, activation of Toll-like receptors (TLRs), the cGAS-STING signaling pathway, interferon (IFN)-mediated antiviral effector functions, and activation of innate immune cells such as natural killer (NK) cells and dendritic cells (DCs). Crucially, however, HSV-2 counteracts these host defenses by expressing immune modulatory proteins (e.g., ICP0, ICP27, ICP35) that target key host antiviral signaling pathways, thereby affecting immune evasion. Within the adaptive immune response, neutralizing antibodies generated by the humoral immunity can provide localized protection at mucosal sites, but their protective efficacy is limited due to sophisticated viral immune evasion mechanisms. Cellular immunity, particularly mediated by CD4+ T cells, constitutes the core mechanism for viral clearance and suppression of recurrent outbreaks. Notably, tissue-resident memory T cells (TRMs) play a pivotal role in controlling the reactivation of latent HSV-2 within the ganglia. This review integrates current research advances to delineate the innate and adaptive immune mechanisms engaged during HSV-2 infection from the perspective of the dynamic host\u2013virus interplay, with an ultimate aim to provide a theoretical foundation informing the rational development of preventive vaccines and therapeutic agents against HSV-2.<\/jats:p>","DOI":"10.3390\/pathogens15030319","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T10:10:43Z","timestamp":1773655843000},"page":"319","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Host Immune Response Mechanisms Against Herpes Simplex Virus Type 2 Infection"],"prefix":"10.3390","volume":"15","author":[{"given":"Yongming","family":"Mei","sequence":"first","affiliation":[{"name":"The Public Experimental Center of Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Teng","sequence":"additional","affiliation":[{"name":"The Public Experimental Center of Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbin","family":"Wang","sequence":"additional","affiliation":[{"name":"The Public Experimental Center of Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"ref_1","first-page":"1473","article-title":"Herpes simplex virus type 2 infection. 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