PMID- 25986633 OWN - NLM STAT- MEDLINE DCOM- 20151215 LR - 20200227 IS - 1465-2099 (Electronic) IS - 0022-1317 (Linking) VI - 96 IP - 9 DP - 2015 Sep TI - Mutation of UL24 impedes the dissemination of acute herpes simplex virus 1 infection from the cornea to neurons of trigeminal ganglia. PG - 2794-2805 LID - 10.1099/vir.0.000189 [doi] AB - 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. FAU - Rochette, Pierre-Alexandre AU - Rochette PA AD - Universite INRS, INRS-Institut Armand-Frappier, 531 boulevard des Prairies, Laval, Quebec H7V 1B7, Canada. FAU - Bourget, Amelie AU - Bourget A AD - Universite INRS, INRS-Institut Armand-Frappier, 531 boulevard des Prairies, Laval, Quebec H7V 1B7, Canada. FAU - Sanabria-Solano, Carolina AU - Sanabria-Solano C AD - Universite INRS, INRS-Institut Armand-Frappier, 531 boulevard des Prairies, Laval, Quebec H7V 1B7, Canada. FAU - Lahmidi, Soumia AU - Lahmidi S AD - Universite INRS, INRS-Institut Armand-Frappier, 531 boulevard des Prairies, Laval, Quebec H7V 1B7, Canada. FAU - Lavallee, Gabriel Ouellet AU - Lavallee GO AD - Universite INRS, INRS-Institut Armand-Frappier, 531 boulevard des Prairies, Laval, Quebec H7V 1B7, Canada. FAU - Pearson, Angela AU - Pearson A AD - Universite INRS, INRS-Institut Armand-Frappier, 531 boulevard des Prairies, Laval, Quebec H7V 1B7, Canada. LA - eng GR - MOP 82924/Canadian Institutes of Health Research/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150518 PL - England TA - J Gen Virol JT - The Journal of general virology JID - 0077340 RN - 0 (UL24 protein, Human herpesvirus 1) RN - 0 (Viral Proteins) SB - IM MH - Animals MH - Cornea/*virology MH - Disease Models, Animal MH - Herpes Simplex/*virology MH - Herpesvirus 1, Human/genetics/*physiology MH - Humans MH - Mice MH - Mutation MH - Neurons/*virology MH - Trigeminal Ganglion/cytology/*virology MH - Viral Proteins/*genetics/metabolism MH - *Virus Replication EDAT- 2015/05/20 06:00 MHDA- 2015/12/17 06:00 CRDT- 2015/05/20 06:00 PHST- 2015/05/20 06:00 [entrez] PHST- 2015/05/20 06:00 [pubmed] PHST- 2015/12/17 06:00 [medline] AID - 10.1099/vir.0.000189 [doi] PST - ppublish SO - J Gen Virol. 2015 Sep;96(9):2794-2805. doi: 10.1099/vir.0.000189. Epub 2015 May 18.