Herpes simplex virus type 1 interaction with myeloid cells in vivo

Shivkumar, Maitreyi, Lawler, Clara, Milho, Ricardo and Stevenson, Philip G. (2016) Herpes simplex virus type 1 interaction with myeloid cells in vivo. Journal of Virology, 90 19: 8661-8672. doi:10.1128/JVI.00881-16

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Author Shivkumar, Maitreyi
Lawler, Clara
Milho, Ricardo
Stevenson, Philip G.
Title Herpes simplex virus type 1 interaction with myeloid cells in vivo
Journal name Journal of Virology   Check publisher's open access policy
ISSN 1098-5514
Publication date 2016-10-01
Year available 2016
Sub-type Article (original research)
DOI 10.1128/JVI.00881-16
Open Access Status File (Publisher version)
Volume 90
Issue 19
Start page 8661
End page 8672
Total pages 12
Place of publication Washington, DC United States
Publisher American Society for Microbiology
Language eng
Abstract Herpes simplex virus 1 (HSV-1) enters mice via olfactory epithelial cells and then colonizes the trigeminal ganglia (TG). Most TG nerve endings are subepithelial, so this colonization implies subepithelial viral spread, where myeloid cells provide an important line of defense. The outcome of infection of myeloid cells by HSV-1 in vitro depends on their differentiation state; the outcome in vivo is unknown. Epithelial HSV-1 commonly infected myeloid cells, and Cre-Lox virus marking showed nose and lung infections passing through LysM-positive (LysM(+)) and CD11c(+) cells. In contrast, subcapsular sinus macrophages (SSMs) exposed to lymph-borne HSV-1 were permissive only when type I interferon (IFN-I) signaling was blocked; normally, their infection was suppressed. Thus, the outcome of myeloid cell infection helped to determine the HSV-1 distribution: subepithelial myeloid cells provided a route of spread from the olfactory epithelium to TG neurons, while SSMs blocked systemic spread.

Herpes simplex virus 1 (HSV-1) infects most people and can cause severe disease. This reflects its persistence in nerve cells that connect to the mouth, nose, eye, and face. Established infection seems impossible to clear. Therefore, we must understand how it starts. This is difficult in humans, but mice show HSV-1 entry via the nose and then spread to its preferred nerve cells. We show that this spread proceeds in part via myeloid cells, which normally function in host defense. Myeloid infection was productive in some settings but was efficiently suppressed by interferon in others. Therefore, interferon acting on myeloid cells can stop HSV-1 spread, and enhancing this defense offers a way to improve infection control.
Formatted abstract
Herpes simplex virus type 1 (HSV-1) enters mice via olfactory epithelial cells, then colonizes the trigeminal ganglia (TG). Most TG nerve endings are subepithelial, so this colonization implies subepithelial viral spread, where myeloid cells provide an important line of defence. The outcome of myeloid cell infection by HSV-1 in vitro depends on their differentiation state; the outcome in vivo is unknown. Epithelial HSV-1 commonly infected myeloid cells, and cre-lox virus marking showed nose and lung infections passing through lysM+ and CD11c+ cells. By contrast subcapsular sinus macrophages (SSM) exposed to lymph-borne HSV-1 were permissive only when type 1 interferon (IFN-I) signaling was blocked; normally their infection was suppressed. Thus the myeloid infection outcome helped to determine HSV-1 distribution: subepithelial myeloid cells provided a route of spread from the olfactory epithelium to TG neurons, while SSM blocked systemic spread.

Importance Herpes simplex virus type 1 (HSV-1) infects most people and can cause severe disease. This reflects its persistence in nerve cells that connect to the mouth, nose, eye and face. Established infection seems impossible to clear. Therefore we must understand how it starts. This is hard in humans, but mice show HSV-1 entry via the nose then spread to its preferred nerve cells. We show that this spread proceeds in part via myeloid cells, which normally function in host defence. Myeloid infection was productive in some settings, but was efficiently suppressed by interferon in others. Therefore interferon acting on myeloid cells can stop HSV-1 spread and enhancing this defence offers a way to improve infection control.
Keyword Virology
Virology
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1064015
FT130100138
BB/J014419/1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
Child Health Research Centre Publications
 
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Created: Fri, 29 Jul 2016, 20:09:10 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences