Shivkumar, M; Lawler, C; Milho, R; Stevenson, PG; (2016) Herpes simplex virus type 1 interaction with myeloid cells in vivo. Journal of Virology , 90 (19) pp. 8661-8672. 10.1128/JVI.00881-16.

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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.

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