Overview

This dissertation, Influenza A Virus Replication and Cytokine Responses in Murine Macrophages in Vitro by Wan-yi, Chan, 陳韻怡, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled Influenza A virus replication and cytokine responses in murine macrophages in vitro Submitted by Chan Wan Yi for the degree of Master of Philosophy at The University of Hong Kong in October 2005 Abstract Background: Lethal influenza A subtype H5N1 has been documented in Hong Kong, and more recently in Vietnam, Thailand, Cambodia and Indonesia. The ability of the virus to affect the host adversely determines its virulence. H5N1 disease in humans is associated with peculiar severity and high mortality. Patients infected with H5N1 demonstrated unusually high serum levels of interferon-gamma-inducible protein-10 (IP-10). In contrast to human influenza virus subtypes H1N1 and H3N2, the H5N1 viruses of 1997 (A/Hong Kong/483/97) was found to be a more potent inducer of pro-inflammatory cytokines and chemokines from human macrophages in vitro. It has been suggested that cytokines dysregulation plays a role in the pathogenesis of H5N1 disease. The mechanisms involved in this differential cytokine induction remain unclear. .Knock-out mouse models would be useful to delineate the signaling pathways involved. As a prerequisite for such experiments, it is important to characterize the virus-mouse macrophage interaction in vitro.Methods: The ability of the influenza viruses to replicate in the murine peritoneal and bone marrow derived macrophages extracted from ICR, Balb/c and C57bl/6N was determined at the levels of viral gene transcription, protein synthesis and infectious virus production. They were obtained from quantitative RT-PCR of viral matrix (M) gene, immunofluorescence staining of viral nucleoprotein (NP) protein and TCID o assay of infected macrophage culture supernatants, respectively. The cytokine and chemokine gene expression profiles elicited by viruses A/HK/483/97, A/Vietnam/I 194/04 with that of human H1N1 (A/HK/54/98) and mouse adapted A/WSN/33 (H1N1) viruses in murine macrophages in vitro were compared using quantitative RT-PCR. Results and Interpretation: The differential hyper-induction of cytokine and chemokine gene expression by H5N1 viruses in macrophages is well demonstrated in the C57bl/6N peritoneal macrophage and bone marrow derived macrophage supplemented by M-CSF. Macrophage from this inbred strain exhibited a differential cytokine gene induction profile similar to that previously demonstrated in primary human macrophage in vitro study. Therefore, C57bl/6N would be a relevant model for studying the pathogenesis of human H5N1 disease. More investigations on the mechanism underlying this pronounced cytokine upregulation can be delineated in knock-out model constructed with C57W/6N background which is now available. In the process of developing an appropriate model for specific research interest, it was discovered that the recent H5N1 (A/Vietnam/1194/04) appears to be more potent to induce IFN-(3 and IP-10 than H5N1/97 virus. This finding may be relevant to the understanding of the pathogenesis of human disease caused by the H5N1 virusesrecently prevalent in South-East Asian Region. The need to advance knowledge in this area is of paramount importance in view of the global pandemic threat currently posed by this H5N1 influenza virus. Word count: 426 DOI: 10.5353/th_b3382993 Subjects: MacrophagesAvian influenza - CytopathologyCytokinesMice - Immunology

Full Product Details

9781361127070

Table of Contents

Reviews

Author Information

Tab Content 6

Customer Reviews

Recent Reviews

Countries Available