Herpes Simplex Virus 1 Replication, Ocular Disease, and Reactivations from Latency Are Restricted Unilaterally after Inoculation of Virus into the Lip

Author:

Poccardi Nolwenn1,Rousseau Antoine123,Haigh Oscar2,Takissian Julie14,Naas Thierry4ORCID,Deback Claire5ORCID,Trouillaud Louise2,Issa Mohammad2,Roubille Simon6,Juillard Franceline6,Efstathiou Stacey7,Lomonte Patrick6,Labetoulle Marc123

Affiliation:

1. Institut de Biologie Intégrative de la Cellule (I2BC), Département de Virologie, CNRS, Gif-sur-Yvette, France

2. CEA-Université Paris Sud, INSERM U1184, Immunology of Viral Infections and Autoimmune Diseases, IDMIT departement, IBFJ, Fontenay-aux-Roses, France

3. Université Paris Sud, Centre Hospitalier Universitaire de Bicêtre, Service d’Ophtalmologie, APHP, DHU Vision & Handicaps, Centre de référence maladies rares en ophtalmologie OPHTARA, Le Kremlin-Bicêtre, France

4. Université Paris Sud, Centre Hospitalier Universitaire de Bicêtre, Service de Bactériologie, APHP, Le Kremlin-Bicêtre, France

5. Université Paris Sud, Hôpital Paul Brousse, Service de Virologie, APHP, Villejuif, France

6. Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx DEVweCAN, Institut NeuroMyoGène (INMG), team Chromatin Assembly, Nuclear Domains, Virus, Lyon, France

7. Division of Virology, Department of Pathology, Cambridge University, Cambridge, United Kingdom

Abstract

Herpetic keratitis (HK) is the leading cause of blindness by an infectious agent in the developed world. This disease can occur after reactivation of herpes simplex virus 1 in the trigeminal ganglia, leading to dissemination of virus to, and infection of, the cornea. A clinical paradox is evidenced by the bilateral presence of latent viral genomes in both trigeminal ganglia, while for any given patient the disease is unilateral with recurrences in a single eye. Our study links the kinetics of early infection to unilateral disease phenomenon and demonstrates protection against viral reactivation when kinetics are exploited. Our results have direct implications in the understanding of human disease pathogenesis and immunotherapeutic strategies for the treatment of HK and viral reactivations.

Funder

Ministere de l'Education Nationale de la Recherche et de Technologie

Societe Francaise d'Ophtalmologie

Fondation pour les Aveugles de Guerre

Fondation de France

Agence Nationale de la Recherche

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Reference47 articles.

1. Roizman B, Knipe DM. 2001. Herpes simplex viruses and their replication, p 2399–2459. In Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman B, Straus SE (ed), Fields virology, 4th ed. Lippincott Williams & Wilkins, Philadelphia, PA.

2. Epidemiology of Ocular Herpes Simplex

3. Herpes Simplex Epithelial and Stromal Keratitis: An Epidemiologic Update

4. Herpesviruses use bidirectional fast-axonal transport to spread in sensory neurons

5. Distribution of Herpes Simplex Virus Type 1 and Varicella Zoster Virus in Ganglia of the Human Head and Neck

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