title: Endocytic Pathways Used by Andes Virus to Enter Primary Human Lung Endothelial Cells.
abstract: Andes virus (ANDV) is the major cause of hantavirus pulmonary syndrome (HPS) in South America. Despite a high fatality rate (up to 40%), no vaccines or antiviral therapies are approved to treat ANDV infection. To understand the role of endocytic pathways in ANDV infection, we used 3 complementary approaches to identify cellular factors required for ANDV entry into human lung microvascular endothelial cells. We screened an siRNA library targeting 140 genes involved in membrane trafficking, and identified 55 genes required for ANDV infection. These genes control the major endocytic pathways, endosomal transport, cell signaling, and cytoskeleton rearrangement. We then used infectious ANDV and retroviral pseudovirions to further characterize the possible involvement of 9 of these genes in the early steps of ANDV entry. In addition, we used markers of cellular endocytosis along with chemical inhibitors of known endocytic pathways to show that ANDV uses multiple routes of entry to infect target cells. These entry mechanisms are mainly clathrin-, dynamin-, and cholesterol-dependent, but can also occur via a clathrin-independent manner.
authors: Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors: Cheng-Feng
authors: http://orcid.org/0000-0002-3617-9124
authors: CF
authors: Chiang
authors: Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors: Mike
authors: M
authors: Flint
authors: Chronic Viral Diseases Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors: Jin-Mann S
authors: JS
authors: Lin
authors: Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors: Christina F
authors: CF
authors: Spiropoulou
mesh_terms: D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D006476:Orthohantavirus / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000166:cytology*; D026901:Membrane Transport Proteins / Q000302:isolation & purification*; D015398:Signal Transduction; D053586:Virus Internalization
chemical_list: D002966:Clathrin; D026901:Membrane Transport Proteins; D002784:Cholesterol; D034281:Dynamins