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Significance Human cytomegalovirus (HCMV)-infected monocytes play a critical role in the hematogenous dissemination of the virus, establishment of persistence, and progression of HCMV-mediated diseases. Here we identify a unique HCMV nuclear translocation pathway in monocytes. HCMV moves from early endosomes to the trans-Golgi network, then to recycling endosomes before its nuclear translocation. Signaling (via c-Src) induced by viral binding of the gH/gL/UL128-131 complex to integrins triggers this unique pathway. Because HCMV is degraded without this signal, we suggest that this distinct signal-induced nuclear translocation functions as a viral evasion pathway in infected monocytes.

Viral binding-induced signaling drives a unique and extended intracellular trafficking pattern during infection of primary monocytes