Emergence of HA mutants during influenza virus pneumonia

International Journal of Clinical and Experimental Pathology

Teruaki Oka¹  Yasuhiro Takeshima¹  Koichiro Kudo¹  Jin Takasaki¹  Yasuhisa Abe¹  Toshie Manabe¹  Toshio Kitazawa¹  Hiroyuki Yoshida¹  Ichiro Morioka¹  Rosa Maria Rivera Rossales¹  Kyoko Shinya¹  Takaaki Nakaya¹  Tateki Ito¹  Maria Eugenia Vázquez Manríquez¹  Akiko Makino¹  Erika Pena Mirabal¹  Makoto Yamashita¹  Anjarath Lorena Higuera Iglesias¹  Kentaro Iwata¹  Motoko Tanaka¹  Shota Nakamura¹  Soichi Arakawa¹ 

关键词: Influenza;    mutant;    hemagglutinin;    pneumonia;    hyperplastic pneumocytes;    syaloglycan receptor;   

DOI  :  

学科分类：生理学与病理学

来源: e-Century Publishing Corporation

【 摘 要 】

During the influenza pandemic of 2009, the number of viral pneumonia cases showed a marked increase in comparison with seasonal influenza viruses. Mutations at amino acid 222 (D222G mutations) in the virus hemagglutinin (HA) molecule, known to alter the receptor-recognition properties of the virus, were detected in a number of the more severely-affected patients in the early phases of the pandemic. To understand the background for the emergence of the mutant amino acid D222G in human lungs, we conducted histological examinations on lung specimens of patients from Mexico who had succumbed in the pandemic. Prominent regenerative and hyperplastic changes in the alveolar type II pneumocytes, which express avian-type sialoglycan receptors in the respiratory tract of severely affected individuals, were observed in the Mexican patients. An infection model utilizing guinea pigs, which was chosen in order to best simulate the sialic acid distribution of severe pneumonia in human patients, demonstrated an increase of D222G mutants and a delay in the diminution of mutants in the lower respiratory tract in comparison to the upper respiratory tract. Our data suggests that the predominance of avian-type sialoglycan receptors in the pneumonic lungs may contribute to the emergence of viral HA mutants. This data comprehensively illustrates the mechanisms for the emergence of mutants in the clinical samples.

【 授权许可】

Unknown