Himanshu Manchanda, Nora Seidel, Markus F. Blaess, Ralf A. Claus, Joerg Linde, Hortense Slevogt, Andreas Sauerbrei, Reinhard Guthke, Michaela Schmidtke
Abstract
Severe influenza associated with strong symptoms and lung inflammation can be caused by intra-host evolution of quasispecies with aspartic acid or glycine in hemagglutinin position 222 (HA-222D/G; H1 numbering). To gain insights into the dynamics of host response to this coevolution and to identify key mechanisms contributing to copathogenesis, the lung transcriptional response of BALB/c mice infected with an A(H1N1)pdm09 isolate consisting HA-222D/G quasispecies was analyzed from days 1 to 12 post infection (p.i). At day 2 p.i. 968 differentially expressed genes (DEGs) were detected. The DEG number declined to 359 at day 4 and reached 1001 at day 7 p.i. prior to recovery. Interestingly, a biphasic expression profile was shown for the majority of these genes. Cytokine assays confirmed these results on protein level exemplarily for two key inflammatory cytokines, interferon gamma and interleukin 6. Using a reverse engineering strategy, a regulatory network was inferred to hypothetically explain the biphasic pattern for selected DEGs. Known regulatory interactions were extracted by Pathway Studio 9.0 and integrated during network inference. The hypothetic gene regulatory network revealed a positive feedback loop of Ifng, Stat1, and Tlr3 gene signaling that was triggered by the HA-G222 variant and correlated with a clinical symptom score indicating disease severity.
Pharmacology, Toxicology and Pharmaceutical Science
2
6%
Other
5
16%
Unknown
7
22%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 August 2016.
All research outputs
#17,812,737
of 22,883,326 outputs
Outputs from Frontiers in Microbiology
#17,261
of 24,918 outputs
Outputs of similar age
#269,378
of 367,231 outputs
Outputs of similar age from Frontiers in Microbiology
#314
of 435 outputs
Altmetric has tracked 22,883,326 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 24,918 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.3. This one is in the 22nd percentile – i.e., 22% of its peers scored the same or lower than it.
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We're also able to compare this research output to 435 others from the same source and published within six weeks on either side of this one. This one is in the 22nd percentile – i.e., 22% of its contemporaries scored the same or lower than it.
