TAILIEUCHUNG - Báo cáo y học: " Identification of critical residues of influenza neuraminidase in viral particle release"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Identification of critical residues of influenza neuraminidase in viral particle release | Tisoncik et al. Virology Journal 2011 8 14 http content 8 1 14 J VIROLOGY JOURNAL RESEARCH Open Access Identification of critical residues of influenza neuraminidase in viral particle release 1 Z 2 1 3 4 z- 3 1 Jennifer R Tisoncik Ying Guo Katie S Cordero Jia Yu Jianwei Wang Youjia Cao Lijun Rong Abstract Background Influenza neuraminidase NA is essential for virus release from its host cells and it is one of the targets for structure-based antiviral drug design. Results In this report we established a pseudoviral particle release assay to study NA function which is based on lentiviral particles pseudotyped with influenza glycoproteins HA and NA as a surrogate system. Through an extensive molecular analysis we sought to characterize important residues governing NA function. We identified five residues of NA 234 241 257 286 and 345 four of which except 345 map away from the active site of NA when projected onto the three-dimensional structure of avian influenza H5N1 NA and substitutions of these residues adversely affected the NA-mediated viral particle release suggesting that these residues are critical for NA enzymatic activity. Conclusion Through extensive chimeric and mutational analyses we have identified several residues which map away from the active site and are critical for NA function. These findings provide new insights into NA-mediated pseudoviral particle release and may have important implications in drug design and therapeutics against influenza infection. Background Influenza virus causes acute respiratory infections resulting in an estimated 300 000 deaths worldwide each year of which approximately 36 000 deaths occur in the United States alone. Equally concerning is the emergence of new viral strains in the human population including the ongoing H5N1 epizootic and swine-origin H1N1 pandemic 1-8 . While influenza vaccines are available they must be reformulated annually to control for antigenic drift and shift of the two major .

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