Shivkumar Maitreyi, Lawler Clara, Milho Ricardo, Stevenson Philip G
Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
School of Chemistry and Molecular Biosciences, University of Queensland and Royal Children's Hospital, Brisbane, Australia.
J Virol. 2016 Sep 12;90(19):8661-72. doi: 10.1128/JVI.00881-16. Print 2016 Oct 1.
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.
单纯疱疹病毒1型（HSV-1）通过嗅觉上皮细胞进入小鼠体内，然后定殖于三叉神经节（TG）。大多数TG神经末梢位于上皮下，因此这种定殖意味着病毒在上皮下扩散，而髓样细胞提供了重要的防御防线。HSV-1在体外感染髓样细胞的结果取决于它们的分化状态；其在体内的结果尚不清楚。上皮性HSV-1通常感染髓样细胞，Cre-Lox病毒标记显示鼻和肺部感染通过LysM阳性（LysM(+)）和CD11c(+)细胞传播。相比之下，暴露于淋巴传播的HSV-1的被膜下窦巨噬细胞（SSM）只有在I型干扰素（IFN-I）信号传导被阻断时才具有感染性；正常情况下，它们的感染会受到抑制。因此，髓样细胞感染的结果有助于确定HSV-1的分布：上皮下髓样细胞提供了从嗅觉上皮到TG神经元的传播途径，而SSM则阻止了病毒的全身传播。
单纯疱疹病毒1型（HSV-1）感染大多数人，并可导致严重疾病。这反映了它在连接口腔、鼻子、眼睛和面部的神经细胞中的持续存在。已建立的感染似乎无法清除。因此，我们必须了解它是如何开始的。这在人类中很难做到，但小鼠显示HSV-1通过鼻子进入，然后传播到其偏好的神经细胞。我们表明，这种传播部分通过髓样细胞进行，髓样细胞通常在宿主防御中发挥作用。髓样细胞感染在某些情况下具有感染性，但在其他情况下则被干扰素有效抑制。因此，作用于髓样细胞的干扰素可以阻止HSV-1的传播，增强这种防御提供了一种改善感染控制的方法。
