scholarly journals Nonmuscle myosin heavy chain IIA facilitates SARS-CoV-2 infection in human pulmonary cells

2021 ◽  
Vol 118 (50) ◽  
pp. e2111011118
Author(s):  
Jian Chen ◽  
Jun Fan ◽  
Zhilu Chen ◽  
Miaomiao Zhang ◽  
Haoran Peng ◽  
...  
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Viral Entry ◽  
Host Factor ◽  
Host Cells ◽  
Dependent Manner ◽  
Nonmuscle Myosin ◽  
Genetic Ablation ◽  
Terminal Domain ◽  
Pulmonary Cells

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), binds to host receptor angiotensin-converting enzyme 2 (ACE2) through its spike (S) glycoprotein, which mediates membrane fusion and viral entry. However, the expression of ACE2 is extremely low in a variety of human tissues, especially in the airways. Thus, other coreceptors and/or cofactors on the surface of host cells may contribute to SARS-CoV-2 infection. Here, we identified nonmuscle myosin heavy chain IIA (MYH9) as an important host factor for SARS-CoV-2 infection of human pulmonary cells by using APEX2 proximity-labeling techniques. Genetic ablation of MYH9 significantly reduced SARS-CoV-2 pseudovirus infection in wild type (WT) A549 and Calu-3 cells, and overexpression of MYH9 enhanced the pseudovirus infection in WT A549 and H1299 cells. MYH9 was colocalized with the SARS-CoV-2 S and directly interacted with SARS-CoV-2 S through the S2 subunit and S1-NTD (N-terminal domain) by its C-terminal domain (designated as PRA). Further experiments suggested that endosomal or myosin inhibitors effectively block the viral entry of SARS-CoV-2 into PRA-A549 cells, while transmembrane protease serine 2 (TMPRSS2) and cathepsin B and L (CatB/L) inhibitors do not, indicating that MYH9 promotes SARS-CoV-2 endocytosis and bypasses TMPRSS2 and CatB/L pathway. Finally, we demonstrated that loss of MYH9 reduces authentic SARS-CoV-2 infection in Calu-3, ACE2-A549, and ACE2-H1299 cells. Together, our results suggest that MYH9 is a candidate host factor for SARS-CoV-2, which mediates the virus entering host cells by endocytosis in an ACE2-dependent manner, and may serve as a potential target for future clinical intervention strategies.

B2 exon splicing of nonmuscle myosin heavy chain IIB is differently regulated in developing and adult rat brain

2000 ◽  
Vol 37 (4) ◽  
pp. 299-306 ◽  
Author(s):  
Taisuke Miyazaki ◽  
Masahiko Watanabe ◽  
Akihiko Yamagishi ◽  
Masayuki Takahashi
Keyword(s):  
Myosin Heavy Chain ◽  
Rat Brain ◽  
Heavy Chain ◽  
Nonmuscle Myosin ◽  
Adult Rat ◽  
Exon Splicing ◽  
Adult Rat Brain

Membrane Nanoparticles Derived from ACE2-rich Cells Block SARS-CoV-2 Infection

2020 ◽  
Author(s):  
Cheng Wang ◽  
Shaobo Wang ◽  
Yin Chen ◽  
Jianqi Zhao ◽  
Songling Han ◽  
...  
Keyword(s):  
Viral Entry ◽  
Inhibitory Concentration ◽  
Cell Metabolism ◽  
Host Cells ◽  
Dependent Manner ◽  
Human Embryonic Kidney ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Dose Dependent

ABSTRACTThe ongoing COVID-19 epidemic worldwide necessitates the development of novel effective agents against SARS-CoV-2. ACE2 is the main receptor of SARS-CoV-2 S1 protein and mediates viral entry into host cells. Herein, the membrane nanoparticles prepared from ACE2-rich cells are discovered with potent capacity to block SARS-CoV-2 infection. The membrane of human embryonic kidney-239T cell highly expressing ACE2 is screened to prepare nanoparticles. The nanomaterial termed HEK-293T-hACE2 NPs contains 265.1 ng mg−1 of ACE2 on the surface and acts as a bait to trap SARS-CoV-2 S1 in a dose-dependent manner, resulting in reduced recruitment of the viral ligand to host cells. Interestingly, SARS-CoV-2 S1 can translocate to the cytoplasm and affect the cell metabolism, which is also inhibited by HEK-293T-hACE2 NPs. Further studies reveal that HEK-293T-hACE2 NPs can efficiently suppress SARS-CoV-2 S pseudovirions entry into human proximal tubular cells and block viral infection with a low half maximal inhibitory concentration. Additionally, this biocompatible membrane nanomaterial is sufficient to block the adherence of SARS-CoV-2 D614G-S1 mutant to sensitive cells. Our study demonstrates a easy-to-acheive memrbane nano-antagonist for curbing SARS-CoV-2, which enriches the existing antiviral arsenal and provides new possibilities to treat COVID-19. Graphical Table of Contents

In Situ Interleukin-6 Transcription in Embryonic Nonmuscle Myosin Heavy Chain Expressing Immature Mesenchyme Cells of Cardiac Myxoma

2000 ◽  
Vol 9 (1) ◽  
pp. 33-37 ◽  
Author(s):  
Jun-ichi Suzuki ◽  
Kei Takayama ◽  
Fujio Mitsui ◽  
Tetsuya Kono ◽  
Yoshikazu Yazaki ◽  
...  
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Interleukin 6 ◽  
Cardiac Myxoma ◽  
Nonmuscle Myosin ◽  
Mesenchyme Cells

scholarly journals Many chronic lymphocytic leukemia antibodies recognize apoptotic cells with exposed nonmuscle myosin heavy chain IIA: implications for patient outcome and cell of origin

Blood ◽  
2010 ◽  
Vol 115 (19) ◽  
pp. 3907-3915 ◽  
Author(s):  
Charles C. Chu ◽  
Rosa Catera ◽  
Lu Zhang ◽  
Sebastien Didier ◽  
Briana M. Agagnina ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Lymphocytic Leukemia ◽  
Apoptotic Cells ◽  
Nonmuscle Myosin ◽  
Cell Of Origin ◽  
Poor Clinical Outcome ◽  
Mutation Status ◽  
Poor Patient Survival

Abstract Many B-cell chronic lymphocytic leukemia (CLL) monoclonal antibodies (mAbs) can be grouped into subsets based on nearly identical stereotyped sequences. Subset 6 CLL mAbs recognize nonmuscle myosin heavy chain IIA (MYHIIA). Herein, we report that during apoptosis, MYHIIA becomes exposed on the cell surface of a subgroup of apoptotic cells, allowing subset 6 CLL mAbs to bind with it. Because other non–subset 6 CLL mAbs interact with apoptotic cells, 26 CLL mAbs, including 24 not belonging to subset 6, were tested for reactivity with MYHIIA-exposed apoptotic cells (MEACs). More than 60% of CLL mAbs bound MEACs well; most of these mAbs expressed unmutated IGHV (15 of 16) and belonged to a stereotyped subset (14 of 16). Binding to MEACs inversely correlated with the degree of IGHV mutation. Interestingly, high binding to MEACs significantly correlated with poor patient survival, suggesting that the basis of IGHV mutation status as a CLL prognostic factor reflects antigen binding. Finally, natural antibodies from human serum also reacted with MEACs. Taken together, our data indicate that a large proportion of CLL clones emerge from natural antibody-producing cells expressing immunoglobulins that recognize MEACs, and that this reactivity is associated with poor clinical outcome.

scholarly journals Function of the Neuron-specific Alternatively Spliced Isoforms of Nonmuscle Myosin II-B during Mouse Brain Development

2006 ◽  
Vol 17 (5) ◽  
pp. 2138-2149 ◽  
Author(s):  
Xuefei Ma ◽  
Sachiyo Kawamoto ◽  
Jorge Uribe ◽  
Robert S. Adelstein
Keyword(s):  
Amino Acids ◽  
Myosin Heavy Chain ◽  
Purkinje Cells ◽  
Heavy Chain ◽  
Myosin Ii ◽  
Nonmuscle Myosin ◽  
Binding Region ◽  
Alternatively Spliced ◽  
Cerebellar Purkinje Cells ◽  
Mouse Brain Development

We report that the alternatively spliced isoforms of nonmuscle myosin heavy chain II-B (NHMC II-B) play distinct roles during mouse brain development. The B1-inserted isoform of NMHC II-B, which contains an insert of 10 amino acids near the ATP-binding region (loop 1) of the myosin heavy chain, is involved in normal migration of facial neurons. In contrast, the B2-inserted isoform, which contains an insert of 21 amino acids near the actin-binding region (loop 2), is important for postnatal development of cerebellar Purkinje cells. Deletion of the B1 alternative exon, together with reduced expression of myosin II-B, results in abnormal migration and consequent protrusion of facial neurons into the fourth ventricle. This protrusion is associated with the development of hydrocephalus. Restoring the amount of myosin II-B expression to wild-type levels prevents these defects, showing the importance of total myosin activity in facial neuron migration. In contrast, deletion of the B2 alternative exon results in abnormal development of cerebellar Purkinje cells. Cells lacking the B2-inserted isoform show reduced numbers of dendritic spines and branches. Some of the B2-ablated Purkinje cells are misplaced in the cerebellar molecular layer. All of the B2-ablated mice demonstrated impaired motor coordination.

scholarly journals Polymorphisms in the Nonmuscle Myosin Heavy Chain 9 Gene (MYH9) Are Associated with Albuminuria in Hypertensive African Americans: The HyperGEN Study

2009 ◽  
Vol 29 (6) ◽  
pp. 626-632 ◽  
Author(s):  
Barry I. Freedman ◽  
Jeffrey B. Kopp ◽  
Cheryl A. Winkler ◽  
George W. Nelson ◽  
D.C. Rao ◽  
...  
Keyword(s):  
African Americans ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Nonmuscle Myosin
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