Abstract
The ability to detect and respond to varying oxygen tension is an essential prerequisite to life. Several mechanisms regulate the cellular response to oxygen including the prolyl hydroxylase domain (PHD)/factor inhibiting HIF (FIH)-hypoxia inducible factor (HIF) pathway, cysteamine (2-aminoethanethiol) dioxygenase (ADO) system, and the lysine-specific demethylases (KDM) 5A and KDM6A. Using a systems-based approach we discuss the literature on oxygen sensing pathways in the context of virus replication in different tissues that experience variable oxygen tension. Current information supports a model where the PHD-HIF pathway enhances the replication of viruses infecting tissues under low oxygen, however, the reverse is true for viruses with a selective tropism for higher oxygen environments. Differences in oxygen tension and associated HIF signaling may play an important role in viral tropism and pathogenesis. Thus, pharmaceutical agents that modulate HIF activity could provide novel treatment options for viral infections and associated pathological conditions.
Highlights
Oxygen is essential for survival and organisms have developed mechanisms to detect and respond to variable oxygen tensions
These studies reported differences in the hypoxia inducible factor (HIF)-dependency of the low oxygen-increase in Hepatitis C Virus (HCV) RNA that most likely reflects the different oxygen tensions used in the experimental models: Vassilaki et al [51] cultured the infected cells at 3% oxygen and showed a minimal role for HIFs in regulating HCV replication, whereas Wilson et al [52] reported a positive role for HIFs in regulating HCV replication at 1% oxygen
Current information suggests that hypoxia preferentially enhances the replication of viruses with a tropism for low oxygen environments, whereas HIFs can dampen the replication of viruses that replicate in tissues with higher oxygen levels
Summary
Oxygen is essential for survival and organisms have developed mechanisms to detect and respond to variable oxygen tensions. Inflammatory responses and tissue damage induced reactive oxygen species (ROS) can all stabilise HIF expression, highlighting the complex interplay between oxygen sensing pathways and viral replication [12,13]. (Moll.cont, NC_001731.1), Orf virus (Orf, NC_005336.1), parvovirus (NC_000883.2), polyomavirus (NC_031757.1), varicella-zoster virus (VZV, and variola virusoxygen (NC_001611.1) These data prompted us to review the current knowledge on how tension impacts viral replication (Figure 3) and how viruses manipulate the PHD-HIF pathway. These data prompted us to review the current knowledge on how oxygen tension impacts viral approach we discuss the literature in the context of viruses infecting and replicating in different tissue replication (Figure 3) and how viruses manipulate the PHD-HIF pathway. Further clinical studies are required to fully examine the relationship between HPV, HIFs and patient outcomes
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call