Cell type-specific biogenesis of novel vesicles containing viral products in human cytomegalovirus infection

摘要: Human cytomegalovirus (HCMV), while highly restricted for the human species, infects an diverse array of cell types in host. Patterns infection are dictated by type infected, but type-specific factors and how they impact tropism specific is poorly understood. Previous studies primary endothelial cells showed that HCMV induces large multivesicular-like bodies (MVBs) incorporate viral products, including dense (DBs) virions. Here we define nature these vesicles using a recombinant virus where UL32, encoding pp150 tegument protein, fused frame with green fluorescent protein (GFP, TB40/E-UL32-GFP). In fibroblasts, UL32-GFP-positive were marked classical markers MVBs, CD63 lysobisphosphatidic acid (LBPA), both MVB markers, as well clathrin LAMP1. Unexpectedly, microvascular (HMVECs) not labeled CD63, LBPA was completely lost from infected cells. We defined UL32-positive cis-Golgi (GM130), lysosome (LAMP1), autophagy (LC3B). These findings suggest UL32-GFP containing MVBs fibroblasts derived canonical endocytic pathway takeover exosomal release pathway. However, HMVECs early biosynthetic exploit less characterized Golgi-LAMP1-associated non- secretory results reveal striking cell-type membrane trafficking differences host pathways exploited HCMV, which may reflect distinct egress.ImportanceHuman (HCMV) herpesvirus that, like all herpesvirus, establishes life-long infection. remains significant cause morbidity mortality immunocompromised seropositivity associated age-related pathology. many biology underlying different patterns Endothelial important target contribute to hematogenous spread tissues. biogenesis virions incorporated into pathway, whereas matures through This work defines basic biological between progeny trafficked out