title: Small interfering RNA inhibition of Andes virus replication.
abstract: Andes virus (ANDV) is the most common causative agent of hantavirus pulmonary syndrome (HPS) in the Americas, and is the only hantavirus associated with human-to-human transmission. Case fatality rates of ANDV-induced HPS are approximately 40%. There are currently no effective vaccines or antivirals against ANDV. Since HPS severity correlates with viral load, we tested small interfering RNA (siRNA) directed against ANDV genes as a potential antiviral strategy. We designed pools of 4 siRNAs targeting each of the ANDV genome segments (S, M, and L), and tested their efficacy in reducing viral replication in vitro. The siRNA pool targeting the S segment reduced viral transcription and replication in Vero-E6 cells more efficiently than those targeting the M and L segments. In contrast, siRNAs targeting the S, M, or L segment were similar in their ability to reduce viral replication in human lung microvascular endothelial cells. Importantly, these siRNAs inhibit ANDV replication even if given after infection. Taken together, our findings indicate that siRNAs targeting the ANDV genome efficiently inhibit ANDV replication, and show promise as a strategy for developing therapeutics against ANDV infection.
authors.affiliation: Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Cheng-Feng
authors.initials: CF
authors.lastname: Chiang
authors.affiliation: Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Cesar G
authors.initials: CG
authors.lastname: Albariňo
authors.affiliation: Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Lo
authors.affiliation: Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Christina F
authors.initials: CF
authors.lastname: Spiropoulou
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D042783:Endothelial Cells / Q000187:drug effects / Q000821:virology; D006476:Orthohantavirus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D018804:Hantavirus Pulmonary Syndrome / Q000473:pathology / Q000821:virology; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000473:pathology / Q000821:virology; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000494:pharmacology*; D012367:RNA, Viral / Q000037:antagonists & inhibitors / Q000235:genetics; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics
chemical_list: D034741:RNA, Small Interfering; D012367:RNA, Viral