Murine Cytomegalovirus Exploits Olfaction To Enter New Hosts
Murine Cytomegalovirus Exploits Olfaction To Enter New Hosts
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DOI：
10.1128/mbio.00251-16
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发表时间：
2016-03-01
期刊：
影响因子：
6.4
通讯作者：
Stevenson，Philip G.
中科院分区：
文献类型：
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作者：
Farrell，Helen E.;Lawler，Clara;Stevenson，Philip G.
病毒通过宿主的环境和社会互动传播。疱疹病毒从它们最早的起源起就在哺乳动物身上定居，这表明它们利用了古老的、常见的途径。巨细胞病毒(CMV)被认为是口头进入新的宿主，但还没有确定地点。我们通过活体成像显示，无论是在实验病毒感染之后还是在自然传播过程中，小鼠巨细胞病毒(MCMV)都是通过鼻腔感染，而不是经口感染。复制缺陷的病毒粒子揭示了嗅觉神经元的主要目标。野生型MCMV的局部鼻腔复制并不广泛，但有快速的全身传播，与巨噬细胞感染有关。然后，唾液腺中保持了长期的、可传播的感染。病毒m131/m129趋化因子同源物影响趋向性，促进鼻腔进入后唾液腺定植，但对鼻腔本身不是必需的。MCMV通过嗅觉传播的能力，以及先前实验中感染小鼠疱疹病毒4型(MuHV-4)和单纯疱疹病毒1型(HSV-1)的嗅觉感染表明，这是哺乳动物疱疹病毒进入的一条常见的、保守的途径。人巨细胞病毒(HCMV)危害免疫功能较差的人群，可损害未出生的胎儿。它感染了大约1%的活产儿。我们缺乏好的疫苗。一个问题是，CMV如何首先进入新的宿主仍不清楚。通常假定是口腔进入，但证据是间接的，而且感染部位尚不清楚。分析人巨细胞病毒的难度使相关动物病毒成为重要的洞察力来源。小鼠巨细胞病毒(MCMV)不是经口腔而是经鼻腔感染。具体地说，它针对的是嗅觉神经元。病毒传播也是一种鼻部感染。和HCMV一样，MCMV通过与肝素结合感染细胞，嗅觉表面对传入的病毒显示肝素，而大多数其他粘膜表面不显示。这些数据建立了对CMV感染的新认识，并为感染控制奠定了基础。
Viruses transmit via the environmental and social interactions of their hosts. Herpesviruses have colonized mammals since their earliest origins, suggesting that they exploit ancient, common pathways. Cytomegaloviruses (CMVs) are assumed to enter new hosts orally, but no site has been identified. We show by live imaging that murine CMV (MCMV) infects nasally rather than orally, both after experimental virus uptake and during natural transmission. Replication-deficient virions revealed the primary target as olfactory neurons. Local, nasal replication by wild-type MCMV was not extensive, but there was rapid systemic spread, associated with macrophage infection. A long-term, transmissible infection was then maintained in the salivary glands. The viral m131/m129 chemokine homolog, which influences tropism, promoted salivary gland colonization after nasal entry but was not required for entryper se. The capacity of MCMV to transmit via olfaction, together with previous demonstrations of experimental olfactory infection by murid herpesvirus 4 (MuHV-4) and herpes simplex virus 1 (HSV-1), suggest that this is a common, conserved route of mammalian herpesvirus entry.IMPORTANCECytomegaloviruses (CMVs) infect most mammals. Human CMV (HCMV) harms people with poor immune function and can damage the unborn fetus. It infects approximately 1% of live births. We lack a good vaccine. One problem is that how CMVs first enter new hosts remains unclear. Oral entry is often assumed, but the evidence is indirect, and no infection site is known. The difficulty of analyzing HCMV makes related animal viruses an important source of insights. Murine CMV (MCMV) infected not orally but nasally. Specifically, it targeted olfactory neurons. Viral transmission was also a nasal infection. Like HCMV, MCMV infected cells by binding to heparan, and olfactory surfaces display heparan to incoming viruses, whereas most other mucosal surfaces do not. These data establish a new understanding of CMV infections and a basis for infection control.