Abstract

BACKGROUND
Highly pathogenic avian H5N1 influenza viruses preferentially infect alveolar type II pneumocytes in human lung. However, it is unknown whether this cellular tropism contributes to high viral virulence because the primary target cells of other influenza viruses have not been systematically studied.
METHODS
We provide the first comparison of the replication, tropism, and cytokine induction of human, highly pathogenic avian influenza A virus subtype H5N1 and other animal influenza A viruses in primary human lung organ cultures.
RESULTS
Subytpe H5N1 and human-adapted subtype H1N1 and H3N2 viruses replicated efficiently in the lung tissue, whereas classic swine and low-pathogenicity avian viruses propagated only poorly. Nevertheless, all viruses examined were detected almost exclusively in type II pneumocytes, with a minor involvement of alveolar macrophages. Infection with avian viruses that have a low and high pathogenicity provoked a pronounced induction of cytokines and chemokines, while human and pandemic H1N1-2009 viruses triggered only weak responses.
CONCLUSIONS
These findings show that differences in the pathogenic potential of influenza A viruses in the human lung cannot be attributed to a distinct cellular tropism. Rather, high or low viral pathogenicity is associated with a strain-specific capacity to productively replicate in type II pneumocytes and to cope with the induced cytokine response.

Links

Publisher Full Text

Authors

Weinheimer VK, Becher A, Tönnies M, Holland G, Knepper J, Bauer TT, Schneider P, Neudecker J, Rückert JC, Szymanski K, Temmesfeld-Wollbrueck B, Gruber AD, Bannert N, Suttorp N, Hippenstiel S, Wolff T, Hocke AC

Institution

Division of Influenza/Respiratory Viruses, Robert Koch Institut, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. isq8@cdc.gov

Source

The Journal of infectious diseases 206:11 2012 Dec 1 pg 1685-94

MeSH

Cytokines
Gene Expression Regulation
Humans
Influenza A virus
Influenza, Human
Lung
Macrophages, Alveolar
Pneumocytes
Tissue Culture Techniques
Viral Tropism
Virulence
Virus Replication

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

22829640