Human cytomegalovirus chemokine, vCXCL-1, modulates normal dissemination kinetics of murine cytomegalovirus in vivo.. Murid betaherpesvirus 1

Human cytomegalovirus (HCMV) is a β-herpesvirus that is a significant pathogen withinnewborn and immune compromised populations. Morbidity associated with HCMVinfection is the consequence of viral dissemination. HCMV has evolved to manipulatethe host immune system to enhance viral dissemination and ensure long-term survivalwithin the host. The immunomodulatory protein vCXCL-1, a viral chemokine functioningprimarily through the CXCR2 chemokine receptor, is hypothesized to attract CXCR2+neutrophils to infection sites, aiding viral dissemination. Neutrophils harbor HCMV invivo, however the interaction between vCXCL-1 and the neutrophil has not beenevaluated in vivo. Using the mouse model and mouse cytomegalovirus (MCMV)infection, we show murine neutrophils harbor and transfer infectious MCMV and virusreplication initiates within this cell type. Utilizing recombinant MCMVs expressingvCXCL-1 from the HCMV strain (Toledo), we demonstrated vCXCL-1 significantlyenhances MCMV dissemination kinetics. Through cellular depletion experiments, weobserve that neutrophils impact dissemination but overall dissemination is largelyneutrophil independent. This work adds neutrophils to the list of innate cells (i.e.,dendritic and macrophages/monocytes) that contribute to MCMV dissemination, butrefutes the hypothesis that neutrophils are the primary cell responding to vCXCL-1.