Type 1 interferon signalling to dendritic cells limits Murid Herpesvirus-4 spread from the olfactory epithelium

Lawler, Clara and Stevenson, Philip G (2017) Type 1 interferon signalling to dendritic cells limits Murid Herpesvirus-4 spread from the olfactory epithelium. Journal of virology, 91 23: 1-14. doi:10.1128/JVI.00951-17

Author Lawler, Clara
Stevenson, Philip G
Title Type 1 interferon signalling to dendritic cells limits Murid Herpesvirus-4 spread from the olfactory epithelium
Journal name Journal of virology   Check publisher's open access policy
ISSN 1098-5514
Publication date 2017-09-13
Year available 2017
Sub-type Article (original research)
DOI 10.1128/JVI.00951-17
Open Access Status Not yet assessed
Volume 91
Issue 23
Start page 1
End page 14
Total pages 14
Place of publication Washington, DC United States
Publisher American Society for Microbiology
Language eng
Abstract Murid Herpesvirus-4 (MuHV-4) is a B cell-tropic gamma-herpesvirus that can be studied in vivo Despite viral evasion, type 1 interferons (IFN-I) limit its spread. After MuHV-4 inoculation into footpads, IFN-I protect lymph node subcapsular sinus macrophages (SSM) against productive infection; after peritoneal inoculation, they protect splenic marginal zone macrophages; and they limit MuHV-4 replication in the lungs. While invasive infections can test specific aspects of host colonization, it is important also to understand natural infection. MuHV-4 taken up spontaneously by alert mice enters them via olfactory neurons. We determined how IFN-I act in this context. Blocking IFN-I signalling did not increase neuronal infection, but allowed its spread to the adjacent respiratory epithelium. In lymph nodes a complete IFN-I signalling block increased MuHV-4 lytic infection in SSM and increased the number of dendritic cells (DC) expressing viral GFP independently of lytic infection. A CD11c(+) cell-directed signalling block increased only DC infection. However this was sufficient to increase down-stream infection, consistent with DC providing the main viral route to B cells. The capacity of IFN-I to limit DC infection indicated that viral IFN-I evasion was only partly effective. Therefore DC are a possible target for IFN-I-based interventions to reduce host colonization.IMPORTANCE Human gamma-herpesviruses infect B cells and cause B cell cancers. Interventions to block virus binding to B cells have not stopped their infection. Therefore we must identify other control points that are relevant to natural infection. Human infections are difficult to analyse. However gamma-herpesviruses colonize all mammals. A related gamma-herpesvirus of mice reaches B cells not directly but via infected dendritic cells. We show that type 1 interferons, an important general anti-viral defence, limit gamma-herpesvirus B cell infection by acting on dendritic cells. Therefore dendritic cell infection is a potential point of interferon-based therapeutic intervention.
Keyword dendritic cell
respiratory tract
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
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Created: Wed, 15 Nov 2017, 13:48:38 EST