Viral Infections and Interferons in the Development of Obesity

Abstract

Obesity is now a prevalent disease worldwide and has a multi-factorial etiology. Several viruses or virus-like agents including members of adenoviridae, herpesviridae, slow virus (prion), and hepatitides, have been associated with obesity; meanwhile obese patients are shown to be more susceptible to viral infections such as during influenza and dengue epidemics. We examined the co-factorial role of viral infections, particularly of the persistent cases, in synergy with high-fat diet in induction of obesity. Antiviral interferons (IFNs), as key immune regulators against viral infections and in autoimmunity, emerge to be a pivotal player in the regulation of adipogenesis. In this review, we examine the recent evidence indicating that gut microbiota uphold intrinsic IFN signaling, which is extensively involved in the regulation of lipid metabolism. However, the prolonged IFN responses during persistent viral infections and obesogenesis comprise reciprocal causality between virus susceptibility and obesity. Furthermore, some IFN subtypes have shown therapeutic potency in their anti-inflammation and anti-obesity activity.

From Influenza Virus to Novel Corona Virus (SARS-CoV-2)–The Contribution of Obesity

“…Leptin affects fat and glucose metabolism and is linked to elevated free fatty acids and glucose levels in obesity and diabetes ( 38 ). Such high levels of glucose suppress the anti-viral type 1 IFN production in PBMCs ( 41 , 42 ) and increase the reactive oxygen species in T cells ( 43 ). Elevated free fatty acids activate TLRs, induce inflammatory cytokines in circulating monocytes and enhance inflammation in T cells ( 44 – 47 ).…”

“…The genetic models of obesity such as the leptin deficient ob/ob mice and leptin receptor-deficient obese db/db mice have increased susceptibility to H1N1 virus infection ( 60 ). Increased leptin levels in obesity may promote infection by lowering anti-viral type 1 IFN through the activation of suppressor of cytokine signaling-3 (SOCS-3) expression ( 42 , 61 ). Indeed disruption of SOCS-3 expression provides protection against influenza A virus infection ( 62 ).…”

“…The role of antiviral IFNs has also been investigated as it is the key to immunity, and suppressed IFN production could be the link for increased infection in obesity ( 42 ). In mice, the reduced IFN response in obese condition was shown to create an ideal microenvironment permitting diversity and emergence of virulent strains and treatment with recombinant IFN reduced the viral diversity ( 63 ).…”

“…The 2002 SARS-CoV infection lowered anti-viral IFNα/β, upregulated TNF receptor, IL-8 and hypoxia related genes ( 83 ). Obesity also lowers the IFNs activity and increases hypoxia in adipocytes leading to a heightened inflammation ( 42 , 84 ). Hence, the combination of the viral infection and obesity probably creates an ideal platform that favors a pro-viral inflammatory “cytokine storm” by lowering the anti-viral immune response.…”

Xenopus Interferon Complex: Inscribing the Amphibiotic Adaption and Species-Specific Pathogenic Pressure in Vertebrate Evolution?

“…In summary, recent studies conclude that the amphibian IFN family has a differential expression pattern and exerts a regulatory role in antiviral, antibacterial, and potential antifungal immune responses [13,16,[59][60][61][62]. In addition, studies in amniotic IFNs also determined the multifunctional properties of antiviral IFNs in the regulation of immune cell development and metabolism, as well as animal pregnancy [68][69][70][71]. Whether amphibian IFN complex evolves to have similar functional diversification warrants further investigations in vertebrate physiology and development.…”