Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Fatal human respiratory disease associated with influenza A subtype H5N1 has been documented in Hong Kong, and more recently in Vietnam, Thailand and Cambodia. We previously demonstrated that patients with H5N1 disease had unusually high serum levels of IP-10 (interferon-gamma-inducible protein-10). Furthermore, when compared with human influenza virus subtype H1N1, the H5N1 viruses in 1997 (A/Hong Kong/483/97) (H5N1/97) were more potent inducers of pro-inflammatory cytokines (e.g. tumor necrosis factor-a) and chemokines (e.g. IP-10) from primary human macrophages in vitro, which suggests that cytokines dysregulation may play a role in pathogenesis of H5N1 disease. Since respiratory epithelial cells are the primary target cell for replication of influenza viruses, it is pertinent to investigate the cytokine induction profile of H5N1 viruses in these cells.

Methods

We used quantitative RT-PCR and ELISA to compare the profile of cytokine and chemokine gene expression induced by H5N1 viruses A/HK/483/97 (H5N1/97), A/Vietnam/1194/04 and A/Vietnam/3046/04 (both H5N1/04) with that of human H1N1 virus in human primary alveolar and bronchial epithelial cells in vitro.

Results

We demonstrated that in comparison to human H1N1 viruses, H5N1/97 and H5N1/04 viruses were more potent inducers of IP-10, interferon beta, RANTES (regulated on activation, normal T cell expressed and secreted) and interleukin 6 (IL-6) in primary human alveolar and bronchial epithelial cells in vitro. Recent H5N1 viruses from Vietnam (H5N1/04) appeared to be even more potent at inducing IP-10 than H5N1/97 virus.

Conclusion

The H5N1/97 and H5N1/04 subtype influenza A viruses are more potent inducers of proinflammatory cytokines and chemokines in primary human respiratory epithelial cells than subtype H1N1 virus. We suggest that this hyper-induction of cytokines may be relevant to the pathogenesis of human H5N1 disease.

Related collections

Most cited references 31

Record: found
Abstract: found
Article: not found

Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus.

Eric CJ Claas, Albert Osterhaus, Ruud van Beek … (1998)

In May, 1997, a 3-year-old boy in Hong Kong was admitted to the hospital and subsequently died from influenza pneumonia, acute respiratory distress syndrome, Reye's syndrome, multiorgan failure, and disseminated intravascular coagulation. An influenza A H5N1 virus was isolated from a tracheal aspirate of the boy. Preceding this incident, avian influenza outbreaks of high mortality were reported from three chicken farms in Hong Kong, and the virus involved was also found to be of the H5 subtype. We carried out an antigenic and molecular comparison of the influenza A H5N1 virus isolated from the boy with one of the viruses isolated from outbreaks of avian influenza by haemagglutination-inhibition and neuraminidase-inhibition assays and nucleotide sequence analysis. Differences were observed in the antigenic reactivities of the viruses by the haemagglutination-inhibition assay. However, nucleotide sequence analysis of all gene segments revealed that the human virus A/Hong Kong/156/97 was genetically closely related to the avian A/chicken/Hong Kong/258/97. Although direct contact between the sick child and affected chickens has not been established, our results suggest transmission of the virus from infected chickens to the child without another intermediate mammalian host acting as a "mixing vessel". This event illustrates the importance of intensive global influenza surveillance.

0 comments Cited 343 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness.

K. Subbarao, A. Klimov, J. Katz … (1998)

An avian H5N1 influenza A virus (A/Hong Kong/156/97) was isolated from a tracheal aspirate obtained from a 3-year-old child in Hong Kong with a fatal illness consistent with influenza. Serologic analysis indicated the presence of an H5 hemagglutinin. All eight RNA segments were derived from an avian influenza A virus. The hemagglutinin contained multiple basic amino acids adjacent to the cleavage site, a feature characteristic of highly pathogenic avian influenza A viruses. The virus caused 87.5 to 100 percent mortality in experimentally inoculated White Plymouth Rock and White Leghorn chickens. These results may have implications for global influenza surveillance and planning for pandemic influenza.

0 comments Cited 317 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Human and avian influenza viruses target different cell types in cultures of human airway epithelium.

Mikhail N Matrosovich, Tatyana Y Matrosovich, Thomas Scott Gray … (2004)

The recent human infections caused by H5N1, H9N2, and H7N7 avian influenza viruses highlighted the continuous threat of new pathogenic influenza viruses emerging from a natural reservoir in birds. It is generally believed that replication of avian influenza viruses in humans is restricted by a poor fit of these viruses to cellular receptors and extracellular inhibitors in the human respiratory tract. However, detailed mechanisms of this restriction remain obscure. Here, using cultures of differentiated human airway epithelial cells, we demonstrated that influenza viruses enter the airway epithelium through specific target cells and that there were striking differences in this respect between human and avian viruses. During the course of a single-cycle infection, human viruses preferentially infected nonciliated cells, whereas avian viruses as well as the egg-adapted human virus variant with an avian virus-like receptor specificity mainly infected ciliated cells. This pattern correlated with the predominant localization of receptors for human viruses (2-6-linked sialic acids) on nonciliated cells and of receptors for avian viruses (2-3-linked sialic acids) on ciliated cells. These findings suggest that although avian influenza viruses can infect human airway epithelium, their replication may be limited by a nonoptimal cellular tropism. Our data throw light on the mechanisms of generation of pandemic viruses from their avian progenitors and open avenues for cell level-oriented studies on the replication and pathogenicity of influenza virus in humans.

0 comments Cited 249 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Respir Res

Title: Respiratory Research

Publisher: BioMed Central (London )

ISSN (Print): 1465-9921

ISSN (Electronic): 1465-993X

Publication date (Print): 2005

Publication date (Electronic): 11 November 2005

Volume: 6

Issue: 1

Page: 135

Affiliations

[1 ]Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region of China

[2 ]Department of Cardiothoracic Surgery, Grantham Hospital, Wong Chuk Hang, Aberdeen, Hong Kong Special Administrative Region of China

[3 ]Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region of China

[4 ]Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region of China

[5 ]National Institute of Hygiene and Epidemiology, Hanoi, Vietnam

Article

Publisher ID: 1465-9921-6-135

DOI: 10.1186/1465-9921-6-135

PMC ID: 1318487

PubMed ID: 16283933

SO-VID: d307b990-4388-46dd-8ecf-38256de4a3df

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells

Read this article at

Abstract

Background

Methods

Results

Conclusion

Related collections

In vitro alveolar region models

Most cited references 31

Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus.

Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness.

Human and avian influenza viruses target different cell types in cultures of human airway epithelium.

Author and article information

Journal

Affiliations

Article

History

Categories

Comments

Comment on this article

Similar content 164

Cited by 158

Most referenced authors 991