Murine Cytomegalovirus Exploits Olfaction To Enter New Hosts

ABSTRACT 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 ide...

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Autores principales:	Helen E. Farrell, Clara Lawler, Cindy S. E. Tan, Kate MacDonald, Kimberley Bruce, Michael Mach, Nick Davis-Poynter, Philip G. Stevenson
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/016a55497c7043a9b8cb9be9fd9c940a
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spelling	oai:doaj.org-article:016a55497c7043a9b8cb9be9fd9c940a2021-11-15T15:41:42ZMurine Cytomegalovirus Exploits Olfaction To Enter New Hosts10.1128/mBio.00251-162150-7511https://doaj.org/article/016a55497c7043a9b8cb9be9fd9c940a2016-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00251-16https://doaj.org/toc/2150-7511ABSTRACT 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, 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.Helen E. FarrellClara LawlerCindy S. E. TanKate MacDonaldKimberley BruceMichael MachNick Davis-PoynterPhilip G. StevensonAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 2 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Helen E. Farrell Clara Lawler Cindy S. E. Tan Kate MacDonald Kimberley Bruce Michael Mach Nick Davis-Poynter Philip G. Stevenson Murine Cytomegalovirus Exploits Olfaction To Enter New Hosts
description	ABSTRACT 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, 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.
format	article
author	Helen E. Farrell Clara Lawler Cindy S. E. Tan Kate MacDonald Kimberley Bruce Michael Mach Nick Davis-Poynter Philip G. Stevenson
author_facet	Helen E. Farrell Clara Lawler Cindy S. E. Tan Kate MacDonald Kimberley Bruce Michael Mach Nick Davis-Poynter Philip G. Stevenson
author_sort	Helen E. Farrell
title	Murine Cytomegalovirus Exploits Olfaction To Enter New Hosts
title_short	Murine Cytomegalovirus Exploits Olfaction To Enter New Hosts
title_full	Murine Cytomegalovirus Exploits Olfaction To Enter New Hosts
title_fullStr	Murine Cytomegalovirus Exploits Olfaction To Enter New Hosts
title_full_unstemmed	Murine Cytomegalovirus Exploits Olfaction To Enter New Hosts
title_sort	murine cytomegalovirus exploits olfaction to enter new hosts
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/016a55497c7043a9b8cb9be9fd9c940a
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Murine Cytomegalovirus Exploits Olfaction To Enter New Hosts

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