title: Herpes simplex virus 1 targets the murine olfactory neuroepithelium for host entry.
abstract: Herpes simplex virus 1 (HSV-1) is a ubiquitous and important human pathogen. It is known to persist in trigeminal ganglia (TG), but how it reaches this site has been difficult to determine, as viral transmission is sporadic, pathogenesis is complicated, and early infection is largely asymptomatic. We used mice to compare the most likely natural HSV-1 host entry routes: oral and nasal. Intranasal infection was 100-fold more efficient than oral and targeted predominantly the olfactory neuroepithelium. Live imaging of HSV-1-expressed luciferase showed infection progressing from the nose to the TG and then reemerging in the facial skin. The brain remained largely luciferase negative throughout. Infected cell tagging by viral Cre recombinase expression in floxed reporter gene mice showed nasal virus routinely reaching the TG and only rarely reaching the olfactory bulbs. Thus, HSV-1 spread from the olfactory neuroepithelium to the TG and reemerged peripherally without causing significant neurological disease. This recapitulation of typical clinical infection suggests that HSV-1 might sometimes also enter humans via the respiratory tract.
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom.
authors.forename: Maitreyi
authors.initials: M
authors.lastname: Shivkumar
authors.forename: Ricardo
authors.initials: R
authors.lastname: Milho
authors.forename: Janet S
authors.initials: JS
authors.lastname: May
authors.forename: Michael P
authors.initials: MP
authors.lastname: Nicoll
authors.forename: Stacey
authors.initials: S
authors.lastname: Efstathiou
authors.forename: Philip G
authors.initials: PG
authors.lastname: Stevenson
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006561:Herpes Simplex / Q000235:genetics / Q000473:pathology / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000472:pathogenicity*; D006801:Humans; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D046569:Neuroepithelial Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D009830:Olfactory Bulb / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D012668:Trigeminal Ganglion / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D053586:Virus Internalization; D014779:Virus Replication
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