Abstract
As the recent outbreak of SARS-CoV-2 has highlighted, the threat of a pandemic event from zoonotic viruses, such as the deadly influenza A/H7N9 virus subtype, continues to be a major global health concern. H7N9 virus strains appear to exhibit greater disease severity in mammalian hosts compared to natural avian hosts, though the exact mechanisms underlying this are somewhat unclear. Knowledge of the H7N9 host-pathogen interactions have mainly been constrained to natural sporadic human infections. To elucidate the cellular immune mechanisms associated with disease severity and progression, we used a ferret model to closely resemble disease outcomes in humans following influenza virus infection. Intriguingly, we observed variable disease outcomes when ferrets were inoculated with the A/Anhui/1/2013 (H7N9) strain. We observed relatively reduced antigen-presenting cell activation in lymphoid tissues which may be correlative with increased disease severity. Additionally, depletions in CD8+ T cells were not apparent in sick animals. This study provides further insight into the ways that lymphocytes maturate and traffic in response to H7N9 infection in the ferret model.
Highlights
In recent years cases of zoonotic strains of avian influenza (AI) causing severe disease in humans have caused significant global concern, with fears that these viruses may lead to devastating pandemic events in future [1, 2]
We aimed to examine the ferret immune response to H7N9 influenza virus infection by analyzing leukocyte population variation associated with disease pathogenesis
H7N9 infection in ferrets resulted in variable clinical symptoms, but overall body weight losses and heightened body temperatures at 48 h postinfection, which are within the typical timeframe for onset of influenza illness in humans
Summary
In recent years cases of zoonotic strains of avian influenza (AI) causing severe disease in humans have caused significant global concern, with fears that these viruses may lead to devastating pandemic events in future [1, 2]. One such group of viruses are strains of H7N9 influenza virus, which have caused over 1,500 cases of infection (with a ∼40% mortality rate) in humans since their first detection in 2013 [3, 4]. Decreases in T lymphocytes are often accompanied by upregulation of several pro-inflammatory cytokines such as interferons
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