The Human Cytomegalovirus Chemokine vCXCL-1 Modulates Normal Dissemination Kinetics of Murine Cytomegalovirus In Vivo

Author:

Jackson Joseph W.1,Hancock Trevor J.1,LaPrade Ellen1,Dogra Pranay12ORCID,Gann Eric R.1,Masi Thomas J.13,Panchanathan Ravichandran4,Miller William E.4ORCID,Wilhelm Steven W.1ORCID,Sparer Tim E.1ORCID

Affiliation:

1. Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA

2. Columbia Center for Translational Immunology, Columbia University, New York, New York, USA

3. University of Tennessee Graduate School of Medicine, Department of Surgery, University of Tennessee Medical Center, Knoxville, Tennessee, USA

4. Department of Molecular Genetics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

Abstract

An adequate in vivo analysis of HCMV’s viral chemokine vCXCL-1 has been lacking. Here we generate recombinant MCMVs expressing vCXCL-1 to study vCXCL-1 function in vivo using MCMV as a surrogate. We demonstrate that vCXCL-1 increases MCMV dissemination kinetics for both primary and secondary dissemination. Additionally, we provide evidence, that the murine neutrophil is largely a bystander in the mouse’s response to vCXCL-1. We confirm the hypothesis that vCXCL-1 is a HCMV virulence factor. Infection of severely immunocompromised mice with MCMVs expressing vCXCL-1 was lethal in more than 50% of infected animals, while all animals infected with parental virus survived during a 12-day period. This work provides needed insights into vCXCL-1 function in vivo .

Funder

HHS | National Institutes of Health

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

Reference65 articles.

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