Murine Cytomegalovirus Exploits Olfaction To Enter New Hosts

作者：Helen E. Farrell, Clara Lawler, Cindy S. E. Tan, Kate Macdonald, Kimberley Bruce, Michael Mach, Nick Davis-Poynter, Philip G. Stevenson · 发表于：mBio · 年份：2016 · DOI：10.1128/mbio.00251-16 · 被引用次数：79 · 研究领域：Cytomegalovirus and herpesvirus research、Herpesvirus Infections and Treatments、Viral-associated cancers and disorders

UNLABELLED: 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 entry per 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. IMPORTANCE: Cytomegaloviruses (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, ...