title: Nonmuscle myosin heavy chain IIA is a critical factor contributing to the efficiency of early infection of severe fever with thrombocytopenia syndrome virus.
abstract: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel phlebovirus in the Bunyaviridae family. Most patients infected by SFTSV present with fever and thrombocytopenia, and up to 30% die due to multiple-organ dysfunction. The mechanisms by which SFTSV enters multiple cell types are unknown. SFTSV contains two species of envelope glycoproteins, Gn (44.2 kDa) and Gc (56 kDa), both of which are encoded by the M segment and are cleaved from a precursor polypeptide (about 116 kDa) in the endoplasmic reticulum (ER). Gn fused with an immunoglobulin Fc tag at its C terminus (Gn-Fc) bound to multiple cells susceptible to the infection of SFTSV and blocked viral infection of human umbilical vein endothelial cells (HUVECs). Immunoprecipitation assays following mass spectrometry analysis showed that Gn binds to nonmuscle myosin heavy chain IIA (NMMHC-IIA), a cellular protein with surface expression in multiple cell types. Small interfering RNA (siRNA) knockdown of NMMHC-IIA, but not the closely related NMMHC-IIB or NMMHC-IIC, reduced SFTSV infection, and NMMHC-IIA specific antibody blocked infection by SFTSV but not other control viruses. Overexpression of NMMHC-IIA in HeLa cells, which show limited susceptivity to SFTSV, markedly enhanced SFTSV infection of the cells. These results show that NMMHC-IIA is critical for the cellular entry of SFTSV. As NMMHC-IIA is essential for the normal functions of platelets and human vascular endothelial cells, it is conceivable that NMMHC-IIA directly contributes to the pathogenesis of SFTSV and may be a useful target for antiviral interventions against the viral infection.
authors.affiliation: National Institute of Biological Sciences, Beijing, ZGC Life Science Park, Changping, Beijing, China.
authors.forename: Yinyan
authors.initials: Y
authors.lastname: Sun
authors.forename: Yonghe
authors.initials: Y
authors.lastname: Qi
authors.forename: Chenxuan
authors.initials: C
authors.lastname: Liu
authors.forename: Wenqing
authors.initials: W
authors.lastname: Gao
authors.forename: Pan
authors.initials: P
authors.lastname: Chen
authors.forename: Liran
authors.initials: L
authors.lastname: Fu
authors.forename: Bo
authors.initials: B
authors.lastname: Peng
authors.forename: Haimin
authors.initials: H
authors.lastname: Wang
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Jing
authors.forename: Guocai
authors.initials: G
authors.lastname: Zhong
authors.forename: Wenhui
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D017931:DNA Primers; D005334:Fever / Q000821:virology*; D006801:Humans; D018613:Microscopy, Confocal; D018995:Myosin Heavy Chains / Q000235:genetics / Q000502:physiology*; D016856:Phlebovirus / Q000472:pathogenicity*; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering / Q000235:genetics; D013921:Thrombocytopenia / Q000821:virology*
chemical_list: D017931:DNA Primers; D034741:RNA, Small Interfering; D018995:Myosin Heavy Chains