tetano
Editor, Senior Moderator
Am J Respir Crit Care Med. 2010 Oct 8. [Epub ahead of print]
Glycan Shielding of the Influenza Virus Hemagglutinin Contributes to Immunopathology in Mice.
Wanzeck K, Boyd KL, McCullers JA.
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, United States.
Abstract
RATIONALE: Pandemic influenza viruses historically have had few potential sites for N-linked glycosylation on the globular head of the hemagglutinin (HA) upon 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 2 or 4 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 4 additional glycosylation sites (+4 virus) elicited significantly lower antibody responses than the wildtype (WT) or +2 virus and was unable to elicit neutralizing antibodies. Mice infected with the +4 virus and then challenged with WT 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.
CONCLUSION: 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 mechanism may have contributed to severe disease in young adults infected with the 2009 pandemic virus.
PMID: 20935106 [PubMed - as supplied by publisher]
Glycan Shielding of the Influenza Virus Hemagglutinin Contributes to Immunopathology in Mice.
Wanzeck K, Boyd KL, McCullers JA.
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, United States.
Abstract
RATIONALE: Pandemic influenza viruses historically have had few potential sites for N-linked glycosylation on the globular head of the hemagglutinin (HA) upon 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 2 or 4 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 4 additional glycosylation sites (+4 virus) elicited significantly lower antibody responses than the wildtype (WT) or +2 virus and was unable to elicit neutralizing antibodies. Mice infected with the +4 virus and then challenged with WT 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.
CONCLUSION: 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 mechanism may have contributed to severe disease in young adults infected with the 2009 pandemic virus.
PMID: 20935106 [PubMed - as supplied by publisher]