Differential Biphasic Transcriptional Host Response Associated with Coevolution of Hemagglutinin Quasispecies of Influenza A Virus

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.

Serratia liquefaciens KM4 Improves Salt Stress Tolerance in Maize by Regulating Redox Potential, Ion Homeostasis, Leaf Gas Exchange and Stress-Related Gene Expression

“…In the current study, Serratia liquefaciens KM4 inoculation significantly enhanced the levels of antioxidant enzymes (APX, CAT, SOD, and POD) and non-enzymatic redox antioxidants (AA and GSH) under saline conditions ( Figure 1 ). These results are supported by the findings of Hashem et al [ 58 ] who recorded induced antioxidants levels in PGPR-inoculated crops. This might help maintaining the photosynthetic electron transport chain, thereby eliminate free radicals [ 59 ].…”

Enhancement of disease resistance, growth potential, and photosynthesis in tomato (Solanum lycopersicum) by inoculation with an endophytic actinobacterium, Streptomyces thermocarboxydus strain BPSAC147

“…The beneficial effects on plant growth mediated by rhizospheric bacteria and fungi have been well documented [4, 5]. The effect of endophytic actinobacteria on photosynthetic efficiency and plant growth, however, has not been widely studied [6, 7]. Endophytes are characterized by their ability to colonize the intracellular spaces and xylem conducting elements in plants without causing any disease symptoms [8, 9].…”

Pulmonary transcriptomic responses indicate a dual role of inflammation in pneumonia development and viral clearance during 2009 pandemic influenza infection

“…Our results support thus the potential use of this mice model for the study of immunopathology in influenza infection and for those works evaluating immunomodulators for the treatment of this disease. While other studies uses a mice adapted influenza strain such as PR8 ( Pommerenke et al, 2012 ) or other mouse passaged 2009 strains, ( Josset et al, 2012a ; Manchanda et al, 2016 ), our study employs a strain obtained directly form a human patient. Mouse adaptation results in increased virulence and lung pathology and also induces a strong host transcriptional response after infection compared with non-adapted influenza strains ( Josset et al, 2012a ).…”