scholarly journals Structural Basis of the Influenza A Virus RNA Polymerase PB2 RNA-binding Domain Containing the Pathogenicity-determinant Lysine 627 Residue

2009 ◽  
Vol 284 (11) ◽  
pp. 6855-6860 ◽  
Author(s):  
Takashi Kuzuhara ◽  
Daisuke Kise ◽  
Hiroko Yoshida ◽  
Takahiro Horita ◽  
Yoshimi Murazaki ◽  
...  
2007 ◽  
Vol 81 (17) ◽  
pp. 9469-9480 ◽  
Author(s):  
Celeste M. Newby ◽  
Leah Sabin ◽  
Andrew Pekosz

ABSTRACT Primary differentiated respiratory epithelial cell cultures closely model the in vivo environment and allow for studies of innate immune responses generated specifically by epithelial cells, the primary cell type infected by human influenza A virus strains. We used primary murine tracheal epithelial cell (mTEC) cultures to investigate antiviral and cytokine responses to influenza A virus infection, focusing on the contribution of the RNA binding domain of the NS1 protein. rWSN NS1 R38A replication is attenuated in mTEC cultures; however, viral antigen is detected predominantly in ciliated cells, similar to wild-type virus. NS1 and NS1 R38A proteins display a primarily cytoplasmic localization in infected mTEC cultures. Increased production of tumor necrosis factor alpha, interleukin-6, and beta interferon is observed during rWSN NS1 R38A infection, and cytokines are secreted in a directional manner. Cytokine pretreatment of mTEC cultures and Vero cells suggest that rWSN NS1 R38A is more sensitive to the presence of antiviral/inflammatory cytokines than wild-type virus. Our results demonstrate that the RNA binding domain is a critical regulator of both cytokine production and cytokine sensitivity during influenza A virus infection of primary tracheal epithelial cells.


2021 ◽  
Vol 12 ◽  
Author(s):  
Qiaozhen Ye ◽  
Shan Lu ◽  
Kevin D. Corbett

The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, is the most severe public health event of the twenty-first century. While effective vaccines against SARS-CoV-2 have been developed, there remains an urgent need for diagnostics to quickly and accurately detect infections. Antigen tests, particularly those that detect the abundant SARS-CoV-2 Nucleocapsid protein, are a proven method for detecting active SARS-CoV-2 infections. Here we report high-resolution crystal structures of three llama-derived single-domain antibodies that bind the SARS-CoV-2 Nucleocapsid protein with high affinity. Each antibody recognizes a specific folded domain of the protein, with two antibodies recognizing the N-terminal RNA binding domain and one recognizing the C-terminal dimerization domain. The two antibodies that recognize the RNA binding domain affect both RNA binding affinity and RNA-mediated phase separation of the Nucleocapsid protein. All three antibodies recognize highly conserved surfaces on the Nucleocapsid protein, suggesting that they could be used to develop affordable diagnostic tests to detect all circulating SARS-CoV-2 variants.


PLoS ONE ◽  
2010 ◽  
Vol 5 (12) ◽  
pp. e15140 ◽  
Author(s):  
Takahito Kashiwagi ◽  
Koyu Hara ◽  
Yoko Nakazono ◽  
Nobuyuki Hamada ◽  
Hiroshi Watanabe

2013 ◽  
Vol 9 (6) ◽  
pp. e1003460 ◽  
Author(s):  
Pei-Ling Tsai ◽  
Ni-Ting Chiou ◽  
Sharon Kuss ◽  
Adolfo García-Sastre ◽  
Kristen W. Lynch ◽  
...  

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