Giuseppe
Emeritus
J Virol. 2009 Oct 7. [Epub ahead of print]
Hemagglutinin-dependent tropism of H5N1 avian influenza virus for human endothelial cells.
Oca?a-Macchi M, Bel M, Guzylack-Piriou L, Ruggli N, Liniger M, McCullough KC, Sakoda Y, Isoda N, Matrosovich M, Summerfield A. - Institute of Virology and Immunoprophylaxis, Mittelh?usern, Switzerland; Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Japan; Institute of Virology, Philipps University, 35043 Marburg, Germany.
Although current H5N1 highly pathogenic avian influenza viruses (HPAIV) are inefficiently transmitted to humans, infected individuals can suffer from severe disease, often progressing rapidly to acute respiratory distress syndrome and multi-organ failure. This is in contrast with human influenza viruses, which in immunocompetent individuals usually only cause a respiratory disease, less aggressive than that observed with avian H5N1 viruses. While the biological basis of inefficient transmission is well documented, the mechanisms by which the H5N1 viruses cause fatal disease remain unclear. In the present study we demonstrate that human pulmonary microvascular endothelial cells (hPMEC) had a clearly higher susceptibility to infection by H5N1 HPAIV when compared to human influenza viruses. This was measurable by de novo intracellular nucleoprotein production and virus replication. It also related to a relatively higher binding capacity to cellular receptors. After infection of hPMEC, cell activation markers E/P-selectin were upregulated, and the proinflammatory cytokines IL-6 as well as IFN-beta, were secreted. H5N1 virus infection was also associated with elevated cell death. Reverse genetics analyses demonstrated a major role for the viral hemagglutinin in this cell tropism. Overall, avian H5N1 viruses have a particular receptor specificity targeting endothelial cells different from human influenza viruses, which could contribute to disease pathogenesis.
PMID: 19812146 [PubMed - as supplied by publisher]
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Hemagglutinin-dependent tropism of H5N1 avian influenza virus for human endothelial cells.
Oca?a-Macchi M, Bel M, Guzylack-Piriou L, Ruggli N, Liniger M, McCullough KC, Sakoda Y, Isoda N, Matrosovich M, Summerfield A. - Institute of Virology and Immunoprophylaxis, Mittelh?usern, Switzerland; Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Japan; Institute of Virology, Philipps University, 35043 Marburg, Germany.
Although current H5N1 highly pathogenic avian influenza viruses (HPAIV) are inefficiently transmitted to humans, infected individuals can suffer from severe disease, often progressing rapidly to acute respiratory distress syndrome and multi-organ failure. This is in contrast with human influenza viruses, which in immunocompetent individuals usually only cause a respiratory disease, less aggressive than that observed with avian H5N1 viruses. While the biological basis of inefficient transmission is well documented, the mechanisms by which the H5N1 viruses cause fatal disease remain unclear. In the present study we demonstrate that human pulmonary microvascular endothelial cells (hPMEC) had a clearly higher susceptibility to infection by H5N1 HPAIV when compared to human influenza viruses. This was measurable by de novo intracellular nucleoprotein production and virus replication. It also related to a relatively higher binding capacity to cellular receptors. After infection of hPMEC, cell activation markers E/P-selectin were upregulated, and the proinflammatory cytokines IL-6 as well as IFN-beta, were secreted. H5N1 virus infection was also associated with elevated cell death. Reverse genetics analyses demonstrated a major role for the viral hemagglutinin in this cell tropism. Overall, avian H5N1 viruses have a particular receptor specificity targeting endothelial cells different from human influenza viruses, which could contribute to disease pathogenesis.
PMID: 19812146 [PubMed - as supplied by publisher]
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