20980523
not annotated - annotated - LINNAEUS only
T cell-mediated protection against lethal 2009 pandemic H1N1 influenza virus infection in a mouse model.
Genetic mutation and reassortment of influenza virus gene segments, in particular those of hemagglutinin (HA) and neuraminidase (NA), that lead to antigenic drift and shift are the major strategies for influenza virus to escape preexisting immunity. The most recent example of such phenomena is the first pandemic of H1N1 influenza of the 21st century, which started in 2009. Cross-reactive antibodies raised against H1N1 viruses circulating before 1930 show protective activity against the 2009 pandemic virus. Cross-reactive T-cell responses can also contribute to protection, but in vivo support of this view is lacking. To explore the protection mechanisms in vivo, we primed mice with H1 and H3 influenza virus isolates and rechallenged them with a virus derived from the 2009 H1N1 A/CA/04/09 virus, named CA/E3/09. We found that priming with influenza viruses of both H1 and H3 homo- and heterosubtypes protected against lethal CA/E3/09 virus challenge. Convalescent-phase sera from these primed mice conferred no neutralization activity in vitro and no protection in vivo. However, T-cell depletion studies suggested that both CD4 and CD8 T cells contributed to the protection. Taken together, these results indicate that cross-reactive T cells established after initial priming with distally related viruses can be a vital component for prevention of disease and control of pandemic H1N1 influenza virus infection. Our results highlight the importance of establishing cross-reactive T-cell responses for protecting against existing or newly emerging pandemic influenza viruses.
Ann file
T1 Species 56 76 H1N1 influenza virus
N1 Reference T1 Taxonomy:11320
T2 Species 144 159 influenza virus
N2 Reference T2 Taxonomy:11309
T3 Species 309 324 influenza virus
N3 Reference T3 Taxonomy:11309
T4 Species 424 438 H1N1 influenza
N4 Reference T4 Taxonomy:11320
T5 Species 524 536 H1N1 viruses
N5 Reference T5 Taxonomy:11320
T7 Species 797 799 H1
N7 Reference T7 Taxonomy:11309
T8 Species 804 822 H3 influenza virus
N8 Reference T8 Taxonomy:11320
T9 Species 889 910 H1N1 A/CA/04/09 virus
N9 Reference T9 Taxonomy:11320
T10 Species 981 983 H1
N10 Reference T10 Taxonomy:11309
T11 Species 1498 1518 H1N1 influenza virus
N11 Reference T11 Taxonomy:11320
T12 Species 92 97 mouse
T13 Species 787 791 mice
T14 Species 1109 1113 mice
N12 Reference T13 Taxonomy:10090 Mus musculus
N13 Reference T14 Taxonomy:10090 Mus musculus
T15 Species 988 990 H3
N14 Reference T15 Taxonomy:11320
T16 Species 955 972 influenza viruses
N15 Reference T16 Taxonomy:11320
T17 Species 1674 1691 influenza viruses
N16 Reference T17 Taxonomy:11320
N17 Reference T12 Taxonomy:10090 Mus musculus
#2 AnnotatorNotes T7 TODO check span: virus related
#3 AnnotatorNotes T8 TODO check span: virus related