Nuclear translocation of HIF-1α induced by influenza A (H1N1) infection is critical to the production of proinflammatory cytokines.

Infection with the influenza A (H1N1) virus is a major challenge for public health because it can cause severe morbidity and even mortality in humans. The over-secretion of inflammatory cytokines (cytokine storm) is considered to be a key contributor to the severe pneumonia caused by H1N1 infection. It has been reported that hypoxia-inducible factor 1-alpha (HIF-1 alpha) is associated with the production of proinflammatory molecules, but whether HIF-1 alpha participates in the acute inflammatory responses against H1N1 infection is still unclear. To investigate the role of HIF-1 alpha in H1N1 infection, the expression and nuclear translocation of HIF-1a in A549 and THP-1 cell lines infected with H1N1 virus were observed. The results showed that without altering the intracellular mRNA or protein expression of HIF-1 alpha, H1N1 infection only induced nuclear translocation of HIF-1 alpha under normal oxygen concentrations. The use of 2-methoxyestradiol (2ME2), a HIF-1 alpha inhibitor that blocks HIF-1a nuclear accumulation, in H1N1-infected cells decreased the mRNA and protein expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 and increased the levels of IL-10. In contrast, H1N1-infected cells under hypoxic conditions had increased HIF-1a nuclear accumulation, increased expression of TNF-a and IL-6 and decreased levels of IL-10. In conclusion, our data implied that in vitro H1N1 infection induced nuclear translocation of HIF-1 alpha without altering the expression of HIF-1 alpha, which may promote the secretion of proinflammatory cytokines during H1N1 infection.