Cytomegalovirus Hijacks CX3CR1hi Patrolling Monocytes as Immune-Privileged Vehicles for Dissemination in Mice

• Published in: Cell host & microbe 2014-03, Vol.15 (3), p.351-362
• Main Authors: Daley-Bauer, Lisa P., Roback, Linda J., Wynn, Grace M., Mocarski, Edward S.
• Format: Article
• Language: English
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2014.02.002

Peripheral blood myelomonocytic cells are important for cytomegalovirus dissemination to distal organs such as salivary glands where persistent replication and shedding dictates transmission patterns. We find that this process is markedly enhanced by the murine cytomegalovirus (MCMV)-encoded CC chemokine, MCK2, which promotes recruitment of CX3CR1hi patrolling monocytes to initial infection sites in the mouse. There, these cells become infected and traffic via the bloodstream to distal sites. In contrast, inflammatory monocytes, the other major myelomonocytic subset, remain virus negative. CX3CR1 deficiency prevents patrolling monocyte migration on the vascular endothelium and interrupts MCMV dissemination to the salivary glands independent of antiviral NK and T cell immune control. In this manner, CX3CR1hi patrolling monocytes serve as immune-privileged vehicles to transport MCMV via the bloodstream to distal organs. MCMV commandeers patrolling monocytes to mediate systemic infection and seed a persistent reservoir essential for horizontal transmission. [Display omitted] •CX3CR1 deficiency disrupts MCMV dissemination from local infection site to salivary glands•Viral MCK2 chemokine recruits CX3CR1hi patrolling monocytes (PMs) to local infection sites•CX3CR1hi PMs harbor infectious MCMV in blood and mediate virus dissemination•CX3CR1hi PM-mediated dissemination promotes viral latency Dissemination via the bloodstream to distal organs is crucial for cytomegalovirus persistence and transmission. Daley-Bauer et al. report that murine cytomegalovirus employs a viral chemokine to recruit CX3CR1-dependent patrolling monocytes to infection sites. These immune-privileged patrolling monocytes are exploited by the virus for transport to spleen and salivary glands.