PMID- 35590057 OWN - NLM STAT- MEDLINE DCOM- 20220523 LR - 20220716 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 12 IP - 1 DP - 2022 May 19 TI - Initial TK-deficient HSV-1 infection in the lip alters contralateral lip challenge immune dynamics. PG - 8489 LID - 10.1038/s41598-022-12597-4 [doi] LID - 8489 AB - Primary infection with herpes simplex type 1 (HSV-1) occurring around the mouth and nose switches rapidly to lifelong latent infection in sensitive trigeminal ganglia (TG) neurons. Sporadic reactivation of these latent reservoirs later in life is the cause of acute infections of the corneal epithelium, which can cause potentially blinding herpes simplex keratitis (HSK). There is no effective vaccine to protect against HSK, and antiviral drugs provide only partial protection against recurrences. We previously engendered an acute disease-free, non-reactivating latent state in mice when challenged with virulent HSV-1 in orofacial mucosa, by priming with non-neurovirulent HSV-1 (TK(del)) before the challenge. Herein, we define the local immune infiltration and inflammatory chemokine production changes after virulent HSV-1 challenge, which were elicited by TK(del) prime. Heightened immunosurveillance before virulent challenge, and early enhanced lymphocyte-enriched infiltration of the challenged lip were induced, which corresponded to attenuation of inflammation in the TG and enhanced viral control. Furthermore, classical latent-phase T cell persistence around latent HSV-1 reservoirs were severely reduced. These findings identify the immune processes that are likely to be responsible for establishing non-reactivating latent HSV-1 reservoirs. Stopping reactivation is essential for development of efficient vaccine strategies against HSV-1. CI - (c) 2022. The Author(s). FAU - Rousseau, Antoine AU - Rousseau A AD - Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB), Commissariat a l'energie Atomique et Aux Energies Renouvelables, Universite Paris-Saclay, INSERM U1184, Fontenay-aux-Roses, France. AD - Service d'Ophtalmologie, Hopital Bicetre, APHP, Universite Paris-Saclay, Le Kremlin-Bicetre, France. FAU - Haigh, Oscar AU - Haigh O AD - Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB), Commissariat a l'energie Atomique et Aux Energies Renouvelables, Universite Paris-Saclay, INSERM U1184, Fontenay-aux-Roses, France. Oscar.Haigh@cea.fr. FAU - Legrand, Roger AU - Legrand R AD - Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB), Commissariat a l'energie Atomique et Aux Energies Renouvelables, Universite Paris-Saclay, INSERM U1184, Fontenay-aux-Roses, France. FAU - Palgen, Jean-Louis AU - Palgen JL AD - Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB), Commissariat a l'energie Atomique et Aux Energies Renouvelables, Universite Paris-Saclay, INSERM U1184, Fontenay-aux-Roses, France. FAU - Lemaitre, Julien AU - Lemaitre J AD - Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB), Commissariat a l'energie Atomique et Aux Energies Renouvelables, Universite Paris-Saclay, INSERM U1184, Fontenay-aux-Roses, France. FAU - Deback, Claire AU - Deback C AD - Service de Virologie, Hopital Paul Brousse, Universite Paris-Saclay, APHP, Villejuif, France. FAU - Oziol, Noemie AU - Oziol N AD - Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB), Commissariat a l'energie Atomique et Aux Energies Renouvelables, Universite Paris-Saclay, INSERM U1184, Fontenay-aux-Roses, France. FAU - Lomonte, Patrick AU - Lomonte P AD - Institut NeuroMyoGene-Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM), CNRS UMR 5261, INSERM U 1513, Universite Claude Bernard Lyon 1, Team Chromatin Dynamics, Nuclear Domains, Virus, Lyon, France. FAU - Labetoulle, Marc AU - Labetoulle M AD - Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB), Commissariat a l'energie Atomique et Aux Energies Renouvelables, Universite Paris-Saclay, INSERM U1184, Fontenay-aux-Roses, France. Marc.Labetoulle@aphp.fr. AD - Service d'Ophtalmologie, Hopital Bicetre, APHP, Universite Paris-Saclay, Le Kremlin-Bicetre, France. Marc.Labetoulle@aphp.fr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220519 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 SB - IM MH - Animals MH - *Herpes Simplex MH - *Herpesvirus 1, Human/physiology MH - *Keratitis, Herpetic MH - Lip MH - Mice MH - Trigeminal Ganglion PMC - PMC9119387 COIS- The authors declare no competing interests. EDAT- 2022/05/20 06:00 MHDA- 2022/05/24 06:00 PMCR- 2022/05/19 CRDT- 2022/05/19 23:37 PHST- 2022/02/03 00:00 [received] PHST- 2022/05/12 00:00 [accepted] PHST- 2022/05/19 23:37 [entrez] PHST- 2022/05/20 06:00 [pubmed] PHST- 2022/05/24 06:00 [medline] PHST- 2022/05/19 00:00 [pmc-release] AID - 10.1038/s41598-022-12597-4 [pii] AID - 12597 [pii] AID - 10.1038/s41598-022-12597-4 [doi] PST - epublish SO - Sci Rep. 2022 May 19;12(1):8489. doi: 10.1038/s41598-022-12597-4.