Interleukin 16 Enhances the Host Susceptibility to Influenza A Virus Infection.

Ran Jia,Long Li,Menghua Xu,Congwei Jiang,Xiaozhen Liang,Lijuan Lu,Chenxu Huang,Jin Xu

doi:10.3389/fmicb.2021.736449

Abstract

Influenza A virus (IAV) is a major respiratory pathogen that causes seasonal and pandemic flu, being a threat to global health. Various viral and cellular factors have been characterized to support or limit IAV infection. Interleukin 16 (IL16) has been known as one of the blood signature biomarkers discriminating systemic inflammation due to viral infection vs. other etiologies. Here, we report that the level of IL16 was elevated in the serum samples, lung homogenates, and bronchoalveolar lavage fluid of IAV-infected mice. IL16 overexpression facilitated IAV replication. Conversely, loss of IL16 reduced the host susceptibility to IAV infection in vitro and in vivo. Furthermore, IL16 deficiency blocked IAV-induced body weight loss and attenuated lung injury in the infected mice. Molecular mechanism analyses further revealed that IL16 could directly inhibit IFN-β transcription and suppress the expression of IFN-β and IFN-stimulated gene. In conclusion, these findings demonstrate that IL16 is a supporting factor for IAV infection.

Highlights

Influenza A virus (IAV) is a major etiologic pathogen responsible for seasonal flu outbreaks and flu pandemics
IAV PR8-infected mice showed a significant increase in Interleukin 16 (IL16) production in serum samples (Figure 1B), Bronchoalveolar lavage fluid (BALF) samples (Figure 1C), and lung homogenates (Figures 1D,E), indicating that IL16 is elevated during IAV infection in both humans and mice
Given that IAV infection stimulates the production of IL16, we wonder whether IL16 plays any role in IAV infection

Summary

Introduction

Influenza A virus (IAV) is a major etiologic pathogen responsible for seasonal flu outbreaks and flu pandemics. H1N1 and H3N2 are the two most common circulating influenza A virus subtypes among humans and cause a major public health problem each year (Krammer, 2019). Unforeseeable antigen drift and antigen shift enable the virus to mutate and develop drug-resistant mutations (Zaraket et al, 2010, 2016; Hurt et al, 2011; Li et al, 2015). This raises the importance of understanding the cellular mechanisms underlying IAV replication and identifying the new host-targeted therapies

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Results

Conclusion