Human cytomegalovirus (HCMV) is a β-herpesvirus that is a significant pathogen within
newborn and immune compromised populations. Morbidity associated with HCMV
infection is the consequence of viral dissemination. HCMV has evolved to manipulate
the host immune system to enhance viral dissemination and ensure long-term survival
within the host. The immunomodulatory protein vCXCL-1, a viral chemokine functioning
primarily through the CXCR2 chemokine receptor, is hypothesized to attract CXCR2+
neutrophils to infection sites, aiding viral dissemination. Neutrophils harbor HCMV in
vivo, however the interaction between vCXCL-1 and the neutrophil has not been
evaluated in vivo. Using the mouse model and mouse cytomegalovirus (MCMV)
infection, we show murine neutrophils harbor and transfer infectious MCMV and virus
replication initiates within this cell type. Utilizing recombinant MCMVs expressing
vCXCL-1 from the HCMV strain (Toledo), we demonstrated vCXCL-1 significantly
enhances MCMV dissemination kinetics. Through cellular depletion experiments, we
observe that neutrophils impact dissemination but overall dissemination is largely
neutrophil independent. This work adds neutrophils to the list of innate cells (i.e.,
dendritic and macrophages/monocytes) that contribute to MCMV dissemination, but
refutes the hypothesis that neutrophils are the primary cell responding to vCXCL-1. Less...