title: Pandemic H1N1 influenza A viruses are resistant to the antiviral activities of innate immune proteins of the collectin and pentraxin superfamilies.
abstract: Acquired immune responses elicited to recent strains of seasonal H1N1 influenza viruses provide limited protection against emerging A(H1N1) pandemic viruses. Accordingly, pre-existing or rapidly induced innate immune defenses are of critical importance in limiting early infection. Respiratory secretions contain proteins of the innate immune system, including members of the collectin and pentraxin superfamilies. These mediate potent antiviral activity and act as an initial barrier to influenza infection. In this study, we have examined the sensitivity of H1N1 viruses, including pandemic virus strains, for their sensitivity to collectins (surfactant protein [SP]-D and mannose-binding lectin [MBL]) and to the pentraxin PTX3. Human SP-D and MBL inhibited virus-induced hemagglutinating activity, blocked the enzymatic activity of the viral neuraminidase, and neutralized the ability of H1N1 viruses to infect human respiratory epithelial cells in a manner that correlated with the degree of glycosylation in the globular head of the hemagglutinin. Recent seasonal H1N1 viruses expressed three to four N-glycosylation sequons on the head of hemagglutinin and were very sensitive to inhibition by SP-D or MBL, whereas A(H1N1) pandemic viruses expressed a single N-glycosylation sequon and were resistant to either collectin. Of interest, both seasonal and pandemic H1N1 viruses were resistant to PTX3. Thus, unlike recent seasonal H1N1 strains of influenza virus, A(H1N1) pandemic viruses are resistant to the antiviral activities of innate immune proteins of the collectin superfamily.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Emma R
authors.initials: ER
authors.lastname: Job
authors.forename: Yi-Mo
authors.initials: YM
authors.lastname: Deng
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Tate
authors.forename: Barbara
authors.initials: B
authors.lastname: Bottazzi
authors.forename: Erika C
authors.initials: EC
authors.lastname: Crouch
authors.forename: Melinda M
authors.initials: MM
authors.lastname: Dean
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Reading
mesh_terms: D002097:C-Reactive Protein / Q000276:immunology* / Q000378:metabolism; D037222:Collectins / Q000276:immunology; D004196:Disease Outbreaks; D004797:Enzyme-Linked Immunosorbent Assay; D006031:Glycosylation; D006386:Hemagglutination Tests; D006387:Hemagglutination, Viral; D006388:Hemagglutinins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D057131:Immune Evasion / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D037601:Mannose-Binding Lectin / Q000276:immunology* / Q000378:metabolism; D009439:Neuraminidase / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D037663:Pulmonary Surfactant-Associated Protein D / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000683:Serum Amyloid P-Component / Q000276:immunology* / Q000378:metabolism; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D037222:Collectins; D006388:Hemagglutinins; D037601:Mannose-Binding Lectin; D009439:Neuraminidase; D037663:Pulmonary Surfactant-Associated Protein D; D000683:Serum Amyloid P-Component; D000099153:Pentraxins