Viral persistence can contribute to chronic disease and promote virus dissemination. Prior work demonstrated that timely clearance of systemic murine norovirus (MNV) infection depends on cellintrinsic type I interferon responses and adaptive immunity. We now find that the capsid of the MNV strain CW3 promotes lytic cell death, release of IL-1α, and increased inflammatory cytokine release. Correspondingly, inflammatory monocytes and neutrophils are recruited to sites of infection in a CW3 capsid-dependent manner. Recruited monocytes and neutrophils are subsequently infected, representing a majority of infected cells in vivo. Furthermore, depletion of continuously recruited inflammatory monocytes or neutrophils from persistently infected Rag1-/- mice reduces viral titers. These data indicate that lytic cell death, inflammation, and recruitment of susceptible cells can serve as the basis of persistent viral infection. Spread to continuously recruited inflammatory cells may be a mechanism of persistence broadly utilized by lytic viruses incapable of establishing latency.
