The Antiviral Role of Galectins toward Influenza A Virus Infection-An Alternative Strategy for Influenza Therapy.

Sheng-Fan Wang,Yu-Ting Lin,Jason C. Huang,Zih-Syuan Yang,Wen-Hung Wang,Chih-Yen Lin,Fu-Tong Liu,Aspiro Nayim Urbina

doi:10.3390/ph14050490

Abstract

Animal lectins are proteins with carbohydrate recognition activity. Galectins, the β-galactoside binding lectins, are expressed in various cells and have been reported to regulate several immunological and physiological responses. Recently, some galectins have been reported to regulate some viral infections, including influenza A virus (IAV); however, the mechanism is still not fully understood. Thus, we aim to review systemically the roles of galectins in their antiviral functions against IAVs. The PRISMA guidelines were used to select the eligible articles. Results indicated that only Galectin-1, Galectin-3, and Galectin-9 were reported to play a regulatory role in IAV infection. These regulatory effects occur extracellularly, through their carbohydrate recognition domain (CRD) interacting with glycans expressed on the virus surface, as well as endogenously, in a cell–cell interaction manner. The inhibition effects induced by galectins on IAV infection were through blocking virus–host receptors interaction, activation of NLRP-3 inflammasome, augment expression of antiviral genes and related cytokines, as well as stimulation of Tim-3 related signaling to enhance virus-specific T cells and humoral immune response. Combined, this study concludes that currently, only three galectins have reported antiviral capabilities against IAV infection, thereby having the potential to be applied as an alternative anti-influenza therapeutic strategy.

Highlights

This study indicated that Gal-1 participated in the regulation of cytopathic processes caused by the H1N1pdm09 virus via interaction with cyclin-dependent kinases (CDKs) and cyclins to induce an arrest of the cell cycle at the G0/G1 phase
This study demonstrated that Gal-3 knockout (KO) mice exhibited less inflammation in the lungs and reduced IL-1β levels in bronchoalveolar lavage fluid, compared to the Gal-3 wild-type (WT) mice after receiving H5N1 influenza inoculation
Our study indicates that only a few galectins were reported to participate in the regulation of influenza A virus (IAV) infection, replication, and propagation

Summary

Introduction

Contagious infectious disease caused by the influenza virus. Influenza viruses belong to the Orthomyxoviridae family, with six to eight segments of linear negative-sense, single-stranded RNA and comprise a family of four distinct viruses (influenza A, B, C, and D viruses) [1]. Influenza A and B viruses are the pathogens causing seasonal influenza disease. The seasonal influenza virus epidemics are estimated to cause 3–5 million cases of severe infection and result in 290,000–650,000 deaths annually worldwide [2,3]. Higher mortality rates are seen in the elderly over 65 years old and children under 5 years old, as well as people in developing countries [4]. The burden for seasonal influenza epidemics is substantial and is significantly increased during

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