Zebrafish usp3 loss promotes hypoxic tolerance by disrupting deubiquitination of K63-polyubiquitinated hif-1αa

The hypoxia-inducible factor(HIF)-mediated hypoxia signaling pathway influences oxygen homeostasis in aerobic organisms.This pathway is regulated by several other pathways.Elucidation of its regulation and the underlying mechanisms may provide insights into the strategies of adaptation and tolerance of organisms to hypoxia.In this study,we found that loss of ubiquitin-specific protease 3(usp3)in zebrafish promotes hypoxia tolerance.Zebrafish usp3 specifically binds to hif-1αa and induces its proteasomal degradation,which is dependent on its deubiquitinase activity.This process leads to the suppression of hypoxia signaling under hypoxia.In addition,usp3 catalyzes the deubiquitination of K63-polyubiquitinated hif-1αa.Endogenous evidence indicated that mammalian USP3 behaves like zebrafish usp3 in regulating the activity of HIF-1α.These findings revealed a novel role for usp3 in influencing hypoxia signaling and showed that usp3-mediated HIF-1αdegradation impairs hypoxia signaling,leading to a decrease in hypoxia tolerance.

Oxygen potentiates antiviral ability of zebrafish in response to SVCV infection

Oxygen(O_(2))profoundly influences the physiological processes of aerobic organisms through a range of mechanisms.Recently,increasing evidence has revealed the relationship between viral infection and oxygen levels.However,due to a lack of feasible methods and in vivo models,how oxygen directly affects antiviral capability remains largely unknown.In contrast to terrestrial animals,fish live in water for life,where oxygen levels change more frequently than on land in areas with similar altitude.Therefore,fish appear to be ideal organisms for elucidating the effect of oxygen levels on antiviral responses.In this study,we report that zebrafish under low oxygen conditions are more susceptible to SVCV infection.Further assays indicate that low oxygen tension not only suppresses SVCV-induced IFN activation but also promotes SVCV replication in both zebrafish cell lines and zebrafish.This study provides novel insights into the effect of oxygen on antiviral responses and virus replication.