The number and position of N-linked glycosylation sites in the hemagglutinin determine differential recognition of seasonal and 2009 pandemic H1N1 influenza virus by porcine surfactant protein D

Hillaire, Marine L. B.; Eijk, Martin van; Nieuwkoop, Nella J.; Trierum, Stella E. Vogelzang-van; Fouchier, Ron A. M.; Osterhaus, Albert D. M. E.; Haagsman, Henk P.; Rimmelzwaan, Guus F.

doi:10.1016/j.virusres.2012.08.003

Cited by 16 publications

(15 citation statements)

References 29 publications

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“…This observation could be related to previous works, demonstrating that an increase of the number of glycosites on the HA of H3N2 or H1N1 viruses increases their susceptibility to Supernatant Proteins D (SP-D) neutralization (Hartshorn et al, 2008;Hillaire et al, 2012;Reading et al, 2009;Sun et al, 2013;Tate et al, 2011;Vigerust et al, 2007). To clarify this point, it could be interesting to test the neutralization of our glyV viruses using recombinant SP-D proteins described in previous studies (Crouch et al, 1994;Hartshorn et al, 2008), or bronchoalveolar lavage fluids collected from naive mice.…”

Section: Discussionsupporting

confidence: 78%

Addition of N-glycosylation sites on the globular head of the H5 hemagglutinin induces the escape of highly pathogenic avian influenza A H5N1 viruses from vaccine-induced immunity

et al. 2015

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Highly pathogenic avian influenza A H5N1 viruses remain endemic in poultry in several countries and still constitute a pandemic threat. Since the early 20th century, we experienced four influenza A pandemics. H3N2 and H1N1pdm09 viruses that respectively emerged during 1968 and 2009 pandemics are still responsible for seasonal epidemics. These viruses evolve regularly by substitutions in antigenic sites of the hemagglutinin (HA), which prevent neutralization by antibodies directed against previous strains (antigenic drift). For seasonal H3N2 viruses, an addition of N-glycosylation sites (glycosites) on H3 contributed to this drift. Here, we questioned whether additional glycosites on H5 could induce an escape of H5N1 virus from neutralization, as it was observed for seasonal H3N2 viruses. Seven H5N1 mutants were produced by adding glycosites on H5. The most glycosylated virus escaped from neutralizing antibodies, in vitro and in vivo. Furthermore, a single additional glycosite was responsible for this escape.

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Section: Discussionsupporting

confidence: 78%

Addition of N-glycosylation sites on the globular head of the H5 hemagglutinin induces the escape of highly pathogenic avian influenza A H5N1 viruses from vaccine-induced immunity

et al. 2015

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“…These results are consistent with studies demonstrating that glycosylated viruses are more sensitive to the innate immune activity of collectins present in lung fluid, but replicate equally well in mouse airway macrophages or MDCK cells in vitro (13, 14, 21–23). However, this sensitivity to collectins appears to be dependent on the number and position of the glycosylations added onto the HA (22). Indeed, our results in mice infected with single glycosylations showed attenuation for some of the mutants (e.g.…”

Section: Discussionmentioning

confidence: 99%

Glycosylations in the Globular Head of the Hemagglutinin Protein Modulate the Virulence and Antigenic Properties of the H1N1 Influenza Viruses

et al. 2013

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The global spread of the 2009 pandemic H1N1 (pH1N1) virus in humans increases the likelihood that this influenza virus strain could undergo antigenic drift in the coming years. Previous seasonal H1N1 and H3N2 influenza strains acquired additional glycosylations in the globular head of their hemagglutinin (HA) proteins as they evolved over time; these are believed to shield antigenically relevant regions. We used influenza A/Netherlands/602/2009 recombinant (rpH1N1) viruses to which we added additional HA glycosylation sites reflecting their temporal appearance in previous seasonal H1N1 viruses. Additional glycosylations resulted in substantial attenuation in mice and ferrets, while deleting HA glycosylation sites from a pre-pandemic 1991 seasonal H1N1 influenza virus resulted in increased pathogenicity in mice. Sera from mice infected with wild type (WT) rpH1N1 virus showed a considerable loss of HA inhibitory (HI) activity against rpH1N1 viruses glycosylated at sites 144 or 144-172, indicating that the polyclonal antibody response elicited by WT rpH1N1 HA seems to be directed against an immunodominant region, likely site Sa, shielded by glycosylation at 144. Sera from humans vaccinated with the pH1N1 inactivated vaccine also showed reduced activity against the 144 and 144-172 mutant viruses. Remarkably, the HI activity of sera from virus-infected mice demonstrated that glycosylation at position 144 resulted in the induction of a broader polyclonal response able to cross-neutralize all WT and glycosylation mutant pH1N1 viruses. Mice infected with a recent seasonal virus in which glycosylation sites 71, 142 and 177 were removed, elicited antibodies that protected against challenge with the antigenically distant pH1N1 virus. Thus, acquisition of glycosylation sites in the HA of H1N1 human influenza viruses not only affects their pathogenicity and ability to escape from polyclonal antibodies elicited by previous influenza virus strains, but also their ability to induce cross-reactive antibodies against drifted antigenic variants. These findings provide the basis for designing improved vaccines and immunization strategies capable of protecting against a broader range of influenza virus strains.

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“…They are responsible for the production of surfactant proteins (Crouch et al, 2000) which functions to lower the surface tension between air and alveolar fluid and thus to prevent alveolar collapse at end of the expiration. In addition, surfactant proteins contribute to antiviral defense (Hillaire et al, 2012). Pulmonary surfactant consists of lipids (90–95%) and four surfactant proteins (SP-A, SP-B, SP-C, and SP-D, 5–10%).…”

Section: Infection and Replication Of Influenzamentioning

confidence: 99%

Use of ex vivo and in vitro cultures of the human respiratory tract to study the tropism and host responses of highly pathogenic avian influenza A (H5N1) and other influenza viruses

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et al. 2013

Virus Research

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The number and position of N-linked glycosylation sites in the hemagglutinin determine differential recognition of seasonal and 2009 pandemic H1N1 influenza virus by porcine surfactant protein D

Cited by 16 publications

References 29 publications

Addition of N-glycosylation sites on the globular head of the H5 hemagglutinin induces the escape of highly pathogenic avian influenza A H5N1 viruses from vaccine-induced immunity

Addition of N-glycosylation sites on the globular head of the H5 hemagglutinin induces the escape of highly pathogenic avian influenza A H5N1 viruses from vaccine-induced immunity

Glycosylations in the Globular Head of the Hemagglutinin Protein Modulate the Virulence and Antigenic Properties of the H1N1 Influenza Viruses

Use of ex vivo and in vitro cultures of the human respiratory tract to study the tropism and host responses of highly pathogenic avian influenza A (H5N1) and other influenza viruses

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