Cytomegalovirus Hijacks CX3CR1(hi) Patrolling Monocytes as Immune-Privileged Vehicles for Dissemination in Mice

• Type of Material: Article
• Authors: Lisa P. Daley-Bauer, Emory University; Linda J. Roback, Emory University; Grace M. Wynn, Emory University; Edward S Mocarski, Emory University
• Language: English
• Date: 2014-03-12
• Publisher: Elsevier (Cell Press): 12 month embargo
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: ©2014 Elsevier Inc.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.chom.2014.02.002
• Title of Journal or Parent Work: Cell Host and Microbe
• ISSN: 1931-3128
• Volume: 15
• Issue: 3
• Start Page: 351
• End Page: 362
• Grant/Funding Information: This work was supported by Public Health Service Grant R01 AI020211 and in part by the Flow Cytometry Core Facility of the Emory Vaccine Center.
• Keywords: PERIPHERAL-BLOOD; MURINE MODEL; Microbiology; DETERMINANT; Science & Technology; CHEMOKINE HOMOLOG; LATENCY; BETA CHEMOKINE; INFECTION; REACTIVATION; TRANSFUSION; DENDRITIC CELLS; Virology; Life Sciences & Biomedicine; Parasitology
• Research Categories: Biology, Virology; Biology, Microbiology; Biology, Parasitology

Abstract

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.