Cell type-specific biogenesis of novel vesicles containing viral products in human 1cytomegalovirus infection

摘要: Human cytomegalovirus (HCMV), while highly restricted for the human species, infects an unlimited 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 incorporate viral products including dense 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). Cells were fixed labeled antibodies against subcellular compartment markers imaged confocal super-resolution microscopy. In fibroblasts, UL32-GFP-positive marked classical MVBs, CD63 lysobisphosphatidic acid (LBPA), both MVB markers, as well clathrin LAMP1. Unexpectedly, not CD63, LBPA was completely lost from infected cells. We defined UL32-positive cis-Golgi (GM130), lysosome (LAMP1), autophagy (LC3B). These findings suggest virus-containing MVBs fibroblasts derived canonical endocytic pathway takeover exosomal release pathway. Virus containing HMVECs early biosynthetic exploit less characterized Golgi-LAMP1-associated non-canonical secretory results reveal striking cell-type membrane trafficking differences host pathways exploited HCMV. ImportanceHuman (HCMV) herpesvirus that, like all herpesvirus, establishes life long infection. remains significant cause morbidity mortality immunocompromised seropositivity associated increased risk vascular disease. 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 may outcome