Proinflammatory cytokine response and viral replication in mouse bone marrow derived macrophages infected with influenza H1N1 and H5N1 viruses

Renee W Y Chan; Connie Y H Leung; John M Nicholls; J S Malik Peiris; Michael C W Chan

doi:10.1371/journal.pone.0051057

Proinflammatory cytokine response and viral replication in mouse bone marrow derived macrophages infected with influenza H1N1 and H5N1 viruses

PLoS One. 2012;7(11):e51057. doi: 10.1371/journal.pone.0051057. Epub 2012 Nov 30.

Authors

Renee W Y Chan¹, Connie Y H Leung, John M Nicholls, J S Malik Peiris, Michael C W Chan

Affiliation

¹ Centre of Influenza Research and School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

Abstract

The pathogenesis of human influenza H5N1 virus infection remains poorly understood and controversial. Cytokine dysregulation in human infection has been hypothesized to contribute to disease severity. We developed in vitro cultures of mouse bone marrow derived macrophages (BMDMΦ) from C57BL/6N mouse to compare influenza A (H5N1 and H1N1) virus replication and pro-inflammatory cytokine and chemokine responses. While both H1N1 and H5N1 viruses infected the mouse bone marrow derived macrophages, only the H1N1 virus had showed evidence of productive viral replication from the infected cells. In comparison with human seasonal influenza H1N1 (A/HK/54/98) and mouse adapted influenza H1N1 (A/WSN/33) viruses, the highly pathogenic influenza H5N1 virus (A/HK/483/97) was a more potent inducer of the chemokine, CXCL 10 (IP-10), while there was not a clear differential TNF-α protein expression pattern. Although human influenza viruses rarely cause infection in mice without prior adaption, the use of in vitro cell cultures of primary mouse cells is of interest, especially given the availability of gene-defective (knock-out) mice for specific genes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chemokines / genetics
Chemokines / metabolism
Cytokines / genetics
Cytokines / metabolism*
Female
Fluorescent Antibody Technique
Gene Expression Regulation
Humans
Inflammation Mediators / metabolism*
Influenza A Virus, H1N1 Subtype / physiology*
Influenza A Virus, H5N1 Subtype / physiology*
Influenza, Human / virology
Lectins / metabolism
Macrophages / immunology*
Macrophages / metabolism
Macrophages / pathology
Macrophages / virology*
Mice
Mice, Inbred C57BL
Orthomyxoviridae Infections / immunology
Orthomyxoviridae Infections / pathology
Orthomyxoviridae Infections / virology
Viral Load
Viral Matrix Proteins / genetics
Viral Matrix Proteins / metabolism
Virus Replication / physiology*

Substances

Chemokines
Cytokines
Inflammation Mediators
Lectins
Viral Matrix Proteins

Grants and funding

This work was supported by the AoE Funding (AoE/M-12/06) from the Area of Excellence Scheme of the University Grants Committee, Hong Kong SAR Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.