Glycan shielding of the influenza virus hemagglutinin contributes to immunopathology in mice

Keith Wanzeck, Kelli L. Boyd, Jonathan Mccullers

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Rationale: Pandemic influenza viruses historically have had few potential sites for N-linked glycosylation on the globular head of the hemagglutinin (HA) on emergence from the avian reservoir. Gain of glycans within antigenic sites of the HA during adaptation to the mammalian lung facilitates immune evasion. Objectives: In this study, we sought to determine in mice how exposure to highly glycosylated viruses affects immunity to poorly glycosylated variants to model the emergence of a novel pandemic strain of a circulating subtype. Methods:We engineered the 1968 H3N2 pandemic strain to express an additional two or four potential sites for glycosylation on the globular head of the HA. Mice were infected sequentially with highly glycosylated variants followed by poorly glycosylated variants and monitored for immune responses and disease. Measurements and Main Results: The mutant with four additional glycosylation sites (+4 virus) elicited significantly lower antibody responses than the wild-type or +2 virus and was unable to elicit neutralizing antibodies. Mice infected with the +4 virus and then challenged with wild-type virus were not protected from infection and experienced significant T-cell - mediated immunopathology. Infection with a recent seasonal H1N1 virus followed by infection with the 2009 pandemic H1N1 elicited similar responses. Conclusions: These data suggest that sequential infection with viral strains with different surface glycosylation can prime the host for immunopathology if a neutralizing antibody response matching the T-cell response is not present. This mechanismmayhave contributed to severe disease in young adults infected with the 2009 pandemic virus.

Original languageEnglish (US)
Pages (from-to)767-773
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume183
Issue number6
DOIs
StatePublished - Mar 15 2011

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Hemagglutinins
Orthomyxoviridae
Pandemics
Polysaccharides
Viruses
Glycosylation
Virus Diseases
Neutralizing Antibodies
Antibody Formation
T-Lymphocytes
Immune Evasion
H1N1 Subtype Influenza A Virus
Immune System Diseases
Infection
Young Adult
Immunity
Lung

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Glycan shielding of the influenza virus hemagglutinin contributes to immunopathology in mice. / Wanzeck, Keith; Boyd, Kelli L.; Mccullers, Jonathan.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 183, No. 6, 15.03.2011, p. 767-773.

Research output: Contribution to journalArticle

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