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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 PLoS+One
2013 ; 8
(2
): e56602
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English Wikipedia
Phenotypic differences in virulence and immune response in closely related
clinical isolates of influenza A 2009 H1N1 pandemic viruses in mice
#MMPMID23441208
PLoS One
2013[]; 8
(2
): e56602
PMID23441208
show ga
To capture the possible genotypic and phenotypic differences of the 2009
influenza A virus H1N1 pandemic (H1N1pdm) strains circulating in adult
hospitalized patients, we isolated and sequenced nine H1N1pdm viruses from
patients hospitalized during 2009-2010 with severe influenza pneumonia in
Kentucky. Each viral isolate was characterized in mice along with two additional
H1N1 pandemic strains and one seasonal strain to assess replication and
virulence. All isolates showed similar levels of replication in nasal turbinates
and lung, but varied in their ability to cause morbidity. Further differences
were identified in cytokine and chemokine responses. IL-6 and KC were expressed
early in mice infected with strains associated with higher virulence. Strains
that showed lower pathogenicity in mice had greater IFN?, MIG, and IL-10
responses. A principal component analysis (PCA) of the cytokine and chemokine
profiles revealed 4 immune response phenotypes that correlated with the severity
of disease. A/KY/180/10, which showed the greatest virulence with a rapid onset
of disease progression, was compared in additional studies with A/KY/136/09,
which showed low virulence in mice. Analyses comparing a low (KY/136) versus a
high (KY/180) virulent isolate showed a significant difference in the kinetics of
infection within the lower respiratory tract and immune responses. Notably by 4
DPI, virus titers within the lung, bronchoalveolar lavage fluid (BALf), and cells
within the BAL (BALc) revealed that the KY/136 replicated in BALc, while KY/180
replication persisted in lungs and BALc. In summary, our studies suggest four
phenotypic groups based on immune responses that result in different virulence
outcomes in H1N1pdm isolates with a high degree of genetic similarity. In vitro
studies with two of these isolates suggested that the more virulent isolate,
KY/180, replicates productively in macrophages and this may be a key determinant
in tipping the response toward a more severe disease progression.