A novel pathogenic mechanism of highly pathogenic avian influenza H5N1 viruses involves hemagglutinin mediated resistance to serum innate inhibitors

• Published in: PloS one Vol. 7; no. 5; p. e36318
• Main Authors: Panaampon, Jutatip, Ngaosuwankul, Nathamon, Suptawiwat, Ornpreya, Noisumdaeng, Pirom, Sangsiriwut, Kantima, Siridechadilok, Bunpote, Lerdsamran, Hatairat, Auewarakul, Prasert, Pooruk, Phisanu, Puthavathana, Pilaipan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-05-2012; Public Library of Science (PLoS)
• Subjects: Animals; Antibodies; Antigens, Viral - chemistry; Antigens, Viral - genetics; Antigens, Viral - immunology; Avian flu; Avian influenza; Avian influenza viruses; Biology; Birds; Cell Line; Correlation; Correlation analysis; Deactivation; Disease resistance; Enzymes; Epidemics; Exo- alpha -sialidase; Exo-a-sialidase; Fowl plague; Genetic vectors; Genetics; Glycosylation; Guinea Pigs; Heads; Heat inactivation; Heat treatment; Hemagglutination; Hemagglutinin Glycoproteins, Influenza Virus - chemistry; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Hemagglutinins; Hospitals; Hot Temperature; Humans; Immune system; Inactivation; Infection; Infections; Infectious diseases; Influenza; Influenza A; Influenza A Virus, H1N1 Subtype - chemistry; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H3N2 Subtype - chemistry; Influenza A Virus, H3N2 Subtype - immunology; Influenza A Virus, H5N1 Subtype - genetics; Influenza A Virus, H5N1 Subtype - immunology; Influenza A Virus, H5N1 Subtype - pathogenicity; Influenza in Birds - virology; Influenza virus; Influenza, Human - virology; Inhibition; Inhibitors; Laboratories; Lectins; Medicine; Models, Molecular; Nucleoproteins; Organs; Pandemics; Plasmids; Preventive medicine; Protein Structure, Tertiary; Proteins; Recombinant Proteins - immunology; Serum - immunology; Surfactants; Surveillance; Trends; Viral infections; Virulence - immunology; Viruses; Thailand; Bangkok Thailand
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0036318

In this study, the effect of innate serum inhibitors on influenza virus infection was addressed. Seasonal influenza A(H1N1) and A(H3N2), 2009 pandemic A(H1N1) (H1N1pdm) and highly pathogenic avian influenza (HPAI) A(H5N1) viruses were tested with guinea pig sera negative for antibodies against all of these viruses as evaluated by hemagglutination-inhibition and microneutralization assays. In the presence of serum inhibitors, the infection by each virus was inhibited differently as measured by the amount of viral nucleoprotein produced in Madin-Darby canine kidney cells. The serum inhibitors inhibited seasonal influenza A(H3N2) virus the most, while the effect was less in seasonal influenza A(H1N1) and H1N1pdm viruses. The suppression by serum inhibitors could be reduced by heat inactivation or treatment with receptor destroying enzyme. In contrast, all H5N1 strains tested were resistant to serum inhibitors. To determine which structure (hemagglutinin (HA) and/or neuraminidase (NA)) on the virus particles that provided the resistance, reverse genetics (rg) was applied to construct chimeric recombinant viruses from A/Puerto Rico/8/1934(H1N1) (PR8) plasmid vectors. rgPR8-H5 HA and rgPR8-H5 HANA were resistant to serum inhibitors while rgPR8-H5 NA and PR8 A(H1N1) parental viruses were sensitive, suggesting that HA of HPAI H5N1 viruses bestowed viral resistance to serum inhibition. These results suggested that the ability to resist serum inhibition might enable the viremic H5N1 viruses to disseminate to distal end organs. The present study also analyzed for correlation between susceptibility to serum inhibitors and number of glycosylation sites present on the globular heads of HA and NA. H3N2 viruses, the subtype with highest susceptibility to serum inhibitors, harbored the highest number of glycosylation sites on the HA globular head. However, this positive correlation cannot be drawn for the other influenza subtypes.