Virus reprogramming of host cellular function is a critical strategy for viral survival and replication. A better understanding of virus-host interaction may provide new potential avenues for the treatment of viral diseases. It has been reported that hypoxia-inducible factor-1 (HIF-1) pathway is activated by a range of pathogens via different mechanisms, but the impact of Influenza A virus on HIF-1 signaling is still unclear. In this study, we observed H1N1 infection stabilized HIF-1 alpha under normoxic conditions. In detail, H1N1 did not increase HIF-1 alpha mRNA transcription, nor impaired posttranslational prolyl hydroxylation or ubiquitination of HIF-1 alpha, but inhibited the function of proteasome, resulting in HIF-1 alpha accumulation. Furthermore, a decreased expression of factor inhibiting HIF-1 (FIH-1), which hydroxylates asparagine 803 within HIF-1 alpha to repress HIF-1 alpha activity, was seen after H1N1 infection. Taken together, these findings reveal a previously unrecognized mechanism of viral activation of the HIF-1 pathway, resembling a hypoxic response in normoxia.
[1]Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Crit Care Med, 650 Xinsongjiang Rd, Shanghai 201620, Peoples R China;
[2]Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol,Minist Educ & Hlth, Dept Pathogen Diag & Biosafety,Shanghai Publ Hlth, Shanghai 201508, Peoples R China;
[3]Fudan Univ, Peoples Hosp Shanghai 5, Dept Resp & Crit Care Med, Shanghai 200240, Peoples R China
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