title: Use of ex vivo and in vitro cultures of the human respiratory tract to study the tropism and host responses of highly pathogenic avian influenza A (H5N1) and other influenza viruses.
abstract: The tropism of influenza viruses for the human respiratory tract is a key determinant of host-range, and consequently, of pathogenesis and transmission. Insights can be obtained from clinical and autopsy studies of human disease and relevant animal models. Ex vivo cultures of the human respiratory tract and in vitro cultures of primary human cells can provide complementary information provided they are physiologically comparable in relevant characteristics to human tissues in vivo, e.g. virus receptor distribution, state of differentiation. We review different experimental models for their physiological relevance and summarize available data using these cultures in relation to highly pathogenic avian influenza H5N1, in comparison where relevant, with other influenza viruses. Transformed continuous cell-lines often differ in important ways to the corresponding tissues in vivo. The state of differentiation of primary human cells (respiratory epithelium, macrophages) can markedly affect virus tropism and host responses. Ex vivo cultures of human respiratory tissues provide a close resemblance to tissues in vivo and may be used to risk assess animal viruses for pandemic threat. Physiological factors (age, inflammation) can markedly affect virus receptor expression and virus tropism. Taken together with data from clinical studies on infected humans and relevant animal models, data from ex vivo and in vitro cultures of human tissues and cells can provide insights into virus transmission and pathogenesis and may provide understanding that leads to novel therapeutic interventions.
authors.affiliation: Department of Pathology, The University of Hong Kong, Hong Kong Special Administrative Region; Centre of Influenza Research, The University of Hong Kong, Hong Kong Special Administrative Region. Electronic address: reneewy@hku.hk.
authors.forename: Renee W Y
authors.initials: RW
authors.lastname: Chan
authors.forename: Michael C W
authors.initials: MC
authors.lastname: Chan
authors.forename: John M
authors.initials: JM
authors.lastname: Nicholls
authors.forename: J S
authors.initials: JS
authors.lastname: Malik Peiris
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000502:physiology*; D007251:Influenza, Human / Q000276:immunology / Q000821:virology*; D009975:Orthomyxoviridae / Q000235:genetics / Q000502:physiology*; D012137:Respiratory System / Q000821:virology*; D056189:Viral Tropism
keywords: H5N1 influenza virus; Host response; Human respiratory epithelial cell in vitro cultures; Human respiratory organ ex vivo cultures; Tissue tropism