PMID- 23903843 OWN - NLM STAT- MEDLINE DCOM- 20131227 LR - 20230620 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 87 IP - 19 DP - 2013 Oct TI - Herpes simplex virus 1 targets the murine olfactory neuroepithelium for host entry. PG - 10477-88 LID - 10.1128/JVI.01748-13 [doi] AB - 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. FAU - Shivkumar, Maitreyi AU - Shivkumar M AD - Division of Virology, Department of Pathology, University of Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom. FAU - Milho, Ricardo AU - Milho R FAU - May, Janet S AU - May JS FAU - Nicoll, Michael P AU - Nicoll MP FAU - Efstathiou, Stacey AU - Efstathiou S FAU - Stevenson, Philip G AU - Stevenson PG LA - eng GR - WT089111MA/WT_/Wellcome Trust/United Kingdom GR - MR/J002232/1/MRC_/Medical Research Council/United Kingdom GR - J014419/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - BB/J014419/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - G0701185/MRC_/Medical Research Council/United Kingdom GR - WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130731 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 SB - IM MH - Animals MH - Blotting, Western MH - Cells, Cultured MH - Enzyme-Linked Immunosorbent Assay MH - Fluorescent Antibody Technique MH - Herpes Simplex/genetics/pathology/*virology MH - Herpesvirus 1, Human/*pathogenicity MH - Humans MH - Immunoenzyme Techniques MH - Kidney/metabolism/pathology/virology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Neuroepithelial Cells/metabolism/pathology/*virology MH - Olfactory Bulb/metabolism/pathology/*virology MH - Trigeminal Ganglion/metabolism/pathology/*virology MH - *Virus Internalization MH - Virus Replication PMC - PMC3807398 EDAT- 2013/08/02 06:00 MHDA- 2013/12/29 06:00 PMCR- 2013/10/01 CRDT- 2013/08/02 06:00 PHST- 2013/08/02 06:00 [entrez] PHST- 2013/08/02 06:00 [pubmed] PHST- 2013/12/29 06:00 [medline] PHST- 2013/10/01 00:00 [pmc-release] AID - JVI.01748-13 [pii] AID - 01748-13 [pii] AID - 10.1128/JVI.01748-13 [doi] PST - ppublish SO - J Virol. 2013 Oct;87(19):10477-88. doi: 10.1128/JVI.01748-13. Epub 2013 Jul 31.