Emergence of HA mutants during influenza virus pneumonia

• Published in: International journal of clinical and experimental pathology Vol. 5; no. 8; pp. 787 - 795
• Main Authors: Manríquez, Maria Eugenia Vázquez, Makino, Akiko, Tanaka, Motoko, Abe, Yasuhisa, Yoshida, Hiroyuki, Morioka, Ichiro, Arakawa, Soichi, Takeshima, Yasuhiro, Iwata, Kentaro, Takasaki, Jin, Manabe, Toshie, Nakaya, Takaaki, Nakamura, Shota, Iglesias, Anjarath Lorena Higuera, Rossales, Rosa Maria Rivera, Mirabal, Erika Pena, Ito, Tateki, Kitazawa, Toshio, Oka, Teruaki, Yamashita, Makoto, Kudo, Koichiro, Shinya, Kyoko
• Format: Journal Article
• Language: English
• Published: United States e-Century Publishing Corporation 01-01-2012
• Subjects: Alveolar Epithelial Cells - virology; Animals; Disease Models, Animal; Disease Outbreaks; Female; Genes, Viral; Guinea Pigs; Hemagglutinins, Viral - genetics; Host-Pathogen Interactions; Humans; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H1N1 Subtype - pathogenicity; Influenza, Human - pathology; Influenza, Human - virology; Madin Darby Canine Kidney Cells; Mutation; Original; Orthomyxoviridae Infections - virology; Pneumonia, Viral - pathology; Pneumonia, Viral - virology; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, Virus - genetics; Receptors, Virus - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral - genetics; hyperplastic pneumocytes; syaloglycan receptor; pneumonia; mutant; Influenza; hemagglutinin
• ISSN: 1936-2625

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.