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2016 ; 7
(2
): e00251-16
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Murine Cytomegalovirus Exploits Olfaction To Enter New Hosts
#MMPMID27118588
Farrell HE
; Lawler C
; Tan CS
; MacDonald K
; Bruce K
; Mach M
; Davis-Poynter N
; Stevenson PG
mBio
2016[Apr]; 7
(2
): e00251-16
PMID27118588
show ga
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.
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