Impact of Hypoxia over Human Viral Infections and Key Cellular Processes

Abstract

Oxygen is essential for aerobic cells, and thus its sensing is critical for the optimal maintenance of vital cellular and tissue processes such as metabolism, pH homeostasis, and angiogenesis, among others. Hypoxia-inducible factors (HIFs) play central roles in oxygen sensing. Under hypoxic conditions, the α subunit of HIFs is stabilized and forms active heterodimers that translocate to the nucleus and regulate the expression of important sets of genes. This process, in turn, will induce several physiological changes intended to adapt to these new and adverse conditions. Over the last decades, numerous studies have reported a close relationship between viral infections and hypoxia. Interestingly, this relation is somewhat bidirectional, with some viruses inducing a hypoxic response to promote their replication, while others inhibit hypoxic cellular responses. Here, we review and discuss the cellular responses to hypoxia and discuss how HIFs can promote a wide range of physiological and transcriptional changes in the cell that modulate numerous human viral infections.

The Hybrid of Cu─TCPP@Mn3O4 for Inflammation Relief by ROS Scavenging and O2 Production: An Efficient Strategy for Antiviral Therapy

“…[ 5 ] “Cytokine storm” is often accompanied by severe tissue hypoxia and massive reactive oxygen species (ROS) production. It is noteworthy that hypoxia may have a considerable side effect during influence A virus (IAV) infections, especially for lung injury, [ 6 ] while excessive accumulation of ROS, such as H 2 O 2 [ 7 ] could also enhance IAV‐induced injury. [ 8 ] Thus, the amelioration of special host environment is important to inhibit IAV infection.…”

Live microscopy of multicellular spheroids with the multi-modal near-infrared nanoparticles reveals differences in oxygenation gradients

“…Hypoxia is associated with several diseases such as ischemia, 5,6 cancer, 7 cardiovascular disorders, 8 inflammatory, 9,10 and infectious diseases. [11][12][13] In solid tumours, uncontrolled cell proliferation, and abnormal vascularisation lead to hypoxia, 14 resulting in poor prognosis, increased cancer cell survival, metabolic switch from oxidative phosphorylation towards aerobic glycolysis, 15 increased cell migration, 16 and resistance to therapy. 17 3D tumour spheroids have been widely used to study oxygenation gradients and hypoxia in vitro, as promising models to bridge the gap between monolayer cultures and intravital experiments, mimicking organ-specific tissue architecture and microenvironment.…”

Interplay between Lipid Metabolism, Lipid Droplets, and DNA Virus Infections

“…Additionally, cellular signaling pathways are also modulated by viruses, such as those related to phosphatidylinositol phosphate kinases (PIKs), mitogen-activated protein kinases, (MAPK) toll-like receptors (TLRs), and interferon (IFN)-related pathways, to name a few [ 28 , 29 , 30 ]. The function of cellular organelles and key cellular processes may also be altered by viral infections, such as the unfolded protein response (UPR), autophagy, apoptosis, mitochondrial function, heat stress, and hypoxia [ 31 , 32 , 33 , 34 , 35 ]. Finally, viral infections modulate important cellular metabolic pathways, such as glucose and lipid metabolism as well [ 36 , 37 ].…”