PMID- 31554680
OWN - NLM
STAT- MEDLINE
DCOM- 20200604
LR  - 20200604
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 93
IP  - 24
DP  - 2019 Dec 15
TI  - Herpes Simplex Virus 1 Replication, Ocular Disease, and Reactivations from 
      Latency Are Restricted Unilaterally after Inoculation of Virus into the Lip.
LID - 10.1128/JVI.01586-19 [doi]
LID - e01586-19
AB  - Ocular herpes simplex keratitis (HSK) is a consequence of viral reactivations 
      from trigeminal ganglia (TG) and occurs almost exclusively in the same eye in 
      humans. In our murine oro-ocular (OO) model, herpes simplex virus 1 (HSV-1) 
      inoculation in one side of the lip propagates virus to infect the ipsilateral TG. 
      Replication here allows infection of the brainstem and infection of the 
      contralateral TG. Interestingly, HSK was observed in our OO model only from the 
      eye ipsilateral to the site of lip infection. Thus, unilateral restriction of 
      HSV-1 may be due to differential kinetics of virus arrival in the ipsilateral 
      versus contralateral TG. We inoculated mice with HSV-1 reporter viruses and then 
      superinfected them to monitor changes in acute- and latent-phase gene expression 
      in TG after superinfection compared to the control (single inoculation). Delaying 
      superinfection by 4 days after initial right lip inoculation elicited failed 
      superinfecting-virus gene expression and eliminated clinical signs of disease. 
      Initial inoculation with thymidine kinase-deficient HSV-1 (TK(del)) completely 
      abolished reactivation of wild-type (WT) superinfecting virus from TG during the 
      latent stage. In light of these seemingly failed infections, viral genome was 
      detected in both TG. Our data demonstrate that inoculation of HSV-1 in the lip 
      propagates virus to both TG, but with delay in reaching the TG contralateral to 
      the side of lip infection. This delay is responsible for restricting viral 
      replication to the ipsilateral TG, which abrogates ocular disease and viral 
      reactivations from the contralateral side. These observations may help to 
      understand why HSK is observed unilaterally in humans, and they provide insight 
      into vaccine strategies to protect against HSK.IMPORTANCE 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.
CI  - Copyright (c) 2019 American Society for Microbiology.
FAU - Poccardi, Nolwenn
AU  - Poccardi N
AD  - Institut de Biologie Integrative de la Cellule (I2BC), Departement de Virologie, 
      CNRS, Gif-sur-Yvette, France.
FAU - Rousseau, Antoine
AU  - Rousseau A
AD  - Institut de Biologie Integrative de la Cellule (I2BC), Departement de Virologie, 
      CNRS, Gif-sur-Yvette, France.
AD  - CEA-Universite Paris Sud, INSERM U1184, Immunology of Viral Infections and 
      Autoimmune Diseases, IDMIT departement, IBFJ, Fontenay-aux-Roses, France.
AD  - Universite Paris Sud, Centre Hospitalier Universitaire de Bicetre, Service 
      d'Ophtalmologie, APHP, DHU Vision & Handicaps, Centre de reference maladies rares 
      en ophtalmologie OPHTARA, Le Kremlin-Bicetre, France.
FAU - Haigh, Oscar
AU  - Haigh O
AD  - CEA-Universite Paris Sud, INSERM U1184, Immunology of Viral Infections and 
      Autoimmune Diseases, IDMIT departement, IBFJ, Fontenay-aux-Roses, France.
FAU - Takissian, Julie
AU  - Takissian J
AD  - Institut de Biologie Integrative de la Cellule (I2BC), Departement de Virologie, 
      CNRS, Gif-sur-Yvette, France.
AD  - Universite Paris Sud, Centre Hospitalier Universitaire de Bicetre, Service de 
      Bacteriologie, APHP, Le Kremlin-Bicetre, France.
FAU - Naas, Thierry
AU  - Naas T
AUID- ORCID: 0000-0001-9937-9572
AD  - Universite Paris Sud, Centre Hospitalier Universitaire de Bicetre, Service de 
      Bacteriologie, APHP, Le Kremlin-Bicetre, France.
FAU - Deback, Claire
AU  - Deback C
AUID- ORCID: 0000-0001-9465-2381
AD  - Universite Paris Sud, Hopital Paul Brousse, Service de Virologie, APHP, 
      Villejuif, France.
FAU - Trouillaud, Louise
AU  - Trouillaud L
AD  - CEA-Universite Paris Sud, INSERM U1184, Immunology of Viral Infections and 
      Autoimmune Diseases, IDMIT departement, IBFJ, Fontenay-aux-Roses, France.
FAU - Issa, Mohammad
AU  - Issa M
AD  - CEA-Universite Paris Sud, INSERM U1184, Immunology of Viral Infections and 
      Autoimmune Diseases, IDMIT departement, IBFJ, Fontenay-aux-Roses, France.
FAU - Roubille, Simon
AU  - Roubille S
AD  - Universite Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx DEVweCAN, 
      Institut NeuroMyoGene (INMG), team Chromatin Assembly, Nuclear Domains, Virus, 
      Lyon, France.
FAU - Juillard, Franceline
AU  - Juillard F
AD  - Universite Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx DEVweCAN, 
      Institut NeuroMyoGene (INMG), team Chromatin Assembly, Nuclear Domains, Virus, 
      Lyon, France.
FAU - Efstathiou, Stacey
AU  - Efstathiou S
AD  - Division of Virology, Department of Pathology, Cambridge University, Cambridge, 
      United Kingdom.
FAU - Lomonte, Patrick
AU  - Lomonte P
AD  - Universite Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx DEVweCAN, 
      Institut NeuroMyoGene (INMG), team Chromatin Assembly, Nuclear Domains, Virus, 
      Lyon, France.
FAU - Labetoulle, Marc
AU  - Labetoulle M
AD  - Institut de Biologie Integrative de la Cellule (I2BC), Departement de Virologie, 
      CNRS, Gif-sur-Yvette, France marc.labetoulle@aphp.fr.
AD  - CEA-Universite Paris Sud, INSERM U1184, Immunology of Viral Infections and 
      Autoimmune Diseases, IDMIT departement, IBFJ, Fontenay-aux-Roses, France.
AD  - Universite Paris Sud, Centre Hospitalier Universitaire de Bicetre, Service 
      d'Ophtalmologie, APHP, DHU Vision & Handicaps, Centre de reference maladies rares 
      en ophtalmologie OPHTARA, Le Kremlin-Bicetre, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191126
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (MicroRNAs)
RN  - 0 (latency associated transcript, herpes simplex virus-1)
SB  - IM
MH  - Animals
MH  - Cornea/virology
MH  - Female
MH  - Gene Expression Regulation, Viral
MH  - Genes, Viral/genetics
MH  - Herpesvirus 1, Human/genetics/*physiology
MH  - Keratitis, Herpetic/*virology
MH  - Lip/*virology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - MicroRNAs/genetics/metabolism
MH  - Trigeminal Ganglion/virology
MH  - Virus Latency/genetics/*physiology
MH  - Virus Replication/*physiology
PMC - PMC6880161
OTO - NOTNLM
OT  - HSV-1
OT  - keratitis
OT  - latency
OT  - neurons
OT  - reactivation
OT  - superinfection
OT  - trigeminal ganglion
EDAT- 2019/09/27 06:00
MHDA- 2020/06/05 06:00
PMCR- 2020/05/26
CRDT- 2019/09/27 06:00
PHST- 2019/09/19 00:00 [received]
PHST- 2019/09/19 00:00 [accepted]
PHST- 2019/09/27 06:00 [pubmed]
PHST- 2020/06/05 06:00 [medline]
PHST- 2019/09/27 06:00 [entrez]
PHST- 2020/05/26 00:00 [pmc-release]
AID - JVI.01586-19 [pii]
AID - 01586-19 [pii]
AID - 10.1128/JVI.01586-19 [doi]
PST - epublish
SO  - J Virol. 2019 Nov 26;93(24):e01586-19. doi: 10.1128/JVI.01586-19. Print 2019 Dec 
      15.