title: Mutation of UL24 impedes the dissemination of acute herpes simplex virus 1 infection from the cornea to neurons of trigeminal ganglia.
abstract: Herpes simplex virus 1 (human herpesvirus 1) initially infects epithelial cells of the mucosa and then goes on to infect sensory neurons leading ultimately to a latent infection in trigeminal ganglia (TG). UL24 is a core herpesvirus gene that has been identified as a determinant of pathogenesis in several Alphaherpesvirinae, although the underlying mechanisms are unknown. In a mouse model of ocular infection, a UL24-deficient virus exhibited a reduction in viral titres in tear films of 1 log10, whilst titres in TG are often below the level of detection. Moreover, the efficiency of reactivation from latency was also severely reduced. Herein, we investigated how UL24 contributed to acute infection of TG. Our results comparing the impact of UL24 on viral titres in eye tissue versus in tear films did not reveal a general defect in virus release from the cornea. We also found that the impairment of replication seen in mouse primary embryonic neurons with a UL24-deficient virus was not more severe than that observed in an epithelial cell line. Rather, in situ histological analyses revealed that infection with a UL24-deficient virus led to a significant reduction in the number of acutely infected neurons at 3 days post-infection (p.i.). Moreover, there was a significant reduction in the number of neurons positive for viral DNA at 2 days p.i. for the UL24-deficient virus as compared with that observed for WT or a rescue virus. Our results supported a model whereby UL24 functions in the dissemination of acute infection from the cornea to neurons in TG.
authors.affiliation: Université INRS, INRS-Institut Armand-Frappier, 531 boulevard des Prairies, Laval, Québec H7V 1B7, Canada.
authors.forename: Pierre-Alexandre
authors.initials: PA
authors.lastname: Rochette
authors.affiliation: Université INRS, INRS-Institut Armand-Frappier, 531 boulevard des Prairies, Laval, Québec H7V 1B7, Canada.
authors.forename: Amélie
authors.initials: A
authors.lastname: Bourget
authors.affiliation: Université INRS, INRS-Institut Armand-Frappier, 531 boulevard des Prairies, Laval, Québec H7V 1B7, Canada.
authors.forename: Carolina
authors.initials: C
authors.lastname: Sanabria-Solano
authors.affiliation: Université INRS, INRS-Institut Armand-Frappier, 531 boulevard des Prairies, Laval, Québec H7V 1B7, Canada.
authors.forename: Soumia
authors.initials: S
authors.lastname: Lahmidi
authors.affiliation: Université INRS, INRS-Institut Armand-Frappier, 531 boulevard des Prairies, Laval, Québec H7V 1B7, Canada.
authors.forename: Gabriel Ouellet
authors.initials: GO
authors.lastname: Lavallée
authors.affiliation: Université INRS, INRS-Institut Armand-Frappier, 531 boulevard des Prairies, Laval, Québec H7V 1B7, Canada.
authors.forename: Angela
authors.initials: A
authors.lastname: Pearson
mesh_terms: D000818:Animals; D003315:Cornea / Q000821:virology*; D004195:Disease Models, Animal; D006561:Herpes Simplex / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D009154:Mutation; D009474:Neurons / Q000821:virology*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
chemical_list: C086267:UL24 protein, Human herpesvirus 1; D014764:Viral Proteins