Murine Cytomegalovirus Exploits Olfaction To Enter New Hosts

Area of Science:

• Virology
• Mammalian Host-Pathogen Interactions
• Neurovirology

Background:

• Cytomegaloviruses (CMVs) infect most mammals, with human CMV (HCMV) posing risks to immunocompromised individuals and fetuses.
• The initial entry route of CMVs into new hosts remains unclear, with oral entry often presumed but lacking direct evidence.
• Studying related animal viruses like murine CMV (MCMV) provides crucial insights into CMV infection dynamics.

Purpose of the Study:

• To determine the primary entry site and initial cellular targets of murine cytomegalovirus (MCMV).
• To investigate the transmission route of MCMV during natural and experimental infection.
• To elucidate the role of viral factors in MCMV tropism and systemic spread.

Main Methods:

• Live imaging of MCMV infection dynamics in vivo.
• Use of replication-deficient virions to identify primary target cells.
• Analysis of viral transmission during experimental and natural infection.
• Investigation of the m131/m129 chemokine homolog's role in MCMV tropism.

Main Results:

• MCMV infects nasally, targeting olfactory neurons, rather than orally.
• Nasal infection leads to rapid systemic spread, involving macrophage infection.
• A long-term, transmissible infection is established in the salivary glands.
• The MCMV m131/m129 chemokine homolog aids salivary gland colonization but not initial entry.

Conclusions:

• Olfactory neurons are the primary entry point for MCMV, challenging the assumed oral route.
• Nasal entry facilitates efficient systemic spread and persistent salivary gland infection.
• Olfactory entry represents a conserved and common route for mammalian herpesvirus transmission.