HIF-1alpha and infectious diseases: a new frontier for the development of new therapies

Abstract

The aim of this review is to show the significant role of HIF-1alpha in inflammatory and infectious diseases. Hypoxia is a physiological characteristic of a wide range of diseases from cancer to infection. Cellular hypoxia is sensed by oxygen-sensitive hydrolase enzymes, which control the protein stability of hypoxia-inducible factor alpha 1 (HIF-1alpha) transcription factors. When stabilized, HIF-1alpha binds with its cofactors to HIF-responsive elements (HREs) in the promoters of target genes to organize a broad ranging transcriptional program in response to the hypoxic environment. HIF-1alpha also plays a regulatory function in response to a diversity of molecular signals of infection and inflammation even under normoxic conditions. HIF-1alpha is stimulated by pro-inflammatory cytokines, growth factors and a wide range of infections. Its induction is a general element of the host response to infection. In this review, we also discuss recent advances in knowledge on HIF-1alpha and inflammatory responses, as well as its direct influence in infectious diseases caused by bacteria, virus, protozoan parasites and fungi.

HIF-1α Modulates Core Metabolism and Virus Replication in Primary Airway Epithelial Cells Infected with Respiratory Syncytial Virus

“…The activity of HIFs as a master regulator of cellular metabolism has been well characterized in a variety of cancer models [ 30 ]. Only over the last decade has the ability of viruses to manipulate this system for the benefit of viral growth been recognized [ 31 ]. For experiments assessing the suppression of HIF-1a and HIF-2a, we used a stable line of telomerase immortalized SAE cells.…”

“…Several viruses, often associated with chronic infections, such as hepatitis C virus, herpesviruses, human papillomavirus and immunodeficiency virus (HIV), have been shown to induce HIF-1α activation, leading to metabolic cellular reprogramming and promotion of virus replication [ 31 , 34 , 35 ]. Influenza virus infection was also able to induce HIF-1α activation in lung carcinoma and monocytic cell lines; however, a lack of lung epithelial cell expression of HIF-1α in a mouse model of influenza infection was associated with enhanced virus replication [ 36 , 37 ].…”

Epigenetic regulator miRNA pattern differences among SARS-CoV, SARS-CoV-2 and SARS-CoV-2 world-wide isolates delineated the mystery behind the epic pathogenicity and distinct clinical characteristics of pandemic COVID-19

“…HIF-1 signaling was also found to be targeted by SARS-CoV-2 miRNAs (Figure 7E, Supplementary figure 1). This pathway is found to be associated with many viral infections as HIF-1 plays an important role in cellular survival during hypoxic conditions (Santos and Andrade, 2017); COVID-19 patients suffer from the lack of oxygens due to breathing complications; so this pathway might play crucial roles to mitigate the condition, but viral miRNA mediated deregulation of this pathway might result in severe consequences.…”

Houttuynia cordata polysaccharide alleviated intestinal injury and modulated intestinal microbiota in H1N1 virus infected mice

“…For protecting major organs, body will redistribute blood from intestine to those organs, causing gut ischemia and hypoxia. Upregulation of hypoxia inducible factor-1α (HIF-1α), a protein induced by hypoxia during inflammation and infections [29] , may cause the loss of tight junction proteins such as ZO-1 [27] . ZO-1, goblet cells and mucus as well as IgA are essential for the intestinal barrier integrity, which can be impaired by the changes of these factors.…”