Human Pulmonary Microvascular Endothelial Cells Support Productive Replication of Highly Pathogenic Avian Influenza Viruses: Possible Involvement in the Pathogenesis of Human H5N1 Virus Infection

Authors

Hui Zeng, National Center for Immunization and Respiratory Diseases - Centers for Disease Control and Prevention, Atlanta, GA
Claudia Pappas, National Center for Immunization and Respiratory Diseases - Centers for Disease Control and Prevention, Atlanta, GA
Jessica A. Belser, National Center for Immunization and Respiratory Diseases - Centers for Disease Control and Prevention, Atlanta, GA
Katherine V. Houser, National Center for Immunization and Respiratory Diseases - Centers for Disease Control and Prevention, Atlanta, GA
Weiming Zhong, National Center for Immunization and Respiratory Diseases - Centers for Disease Control and Prevention, Atlanta, GA
Debra A. Wadford, National Center for Immunization and Respiratory Diseases - Centers for Disease Control and Prevention, Atlanta, GA
Troy Stevens, University of South AlabamaFollow
Ron Balczon, University of South AlabamaFollow
Jacqueline M. Katz, National Center for Immunization and Respiratory Diseases - Centers for Disease Control and Prevention, Atlanta, GA
Terrence M. Tumpey, National Center for Immunization and Respiratory Diseases - Centers for Disease Control and Prevention, Atlanta, GAFollow

Document Type

Article

Publication Title

Journal of Virology

Abstract

Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to cause sporadic human infections with a high fatality rate. Respiratory failure due to acute respiratory distress syndrome (ARDS) is a complication among hospitalized patients. Since progressive pulmonary endothelial damage is the hallmark of ARDS, we investigated host responses following HPAI virus infection of human pulmonary microvascular endothelial cells. Evaluation of these cells for the presence of receptors preferred by influenza virus demonstrated that avian-like (α2-3-linked) receptors were more abundant than human-like (α2-6-linked) receptors. To test the permissiveness of pulmonary endothelial cells to virus infection, we compared the replication of selected seasonal, pandemic (2009 H1N1 and 1918), and potentially pandemic (H5N1) influenza virus strains. We observed that these cells support productive replication only of HPAI H5N1 viruses, which preferentially enter through and are released from the apical surface of polarized human endothelial monolayers. Furthermore, A/Thailand/16/2004 and A/Vietnam/1203/2004 (VN/1203) H5N1 viruses, which exhibit heightened virulence in mammalian models, replicated to higher titers than less virulent H5N1 strains. VN/1203 infection caused a significant decrease in endothelial cell proliferation compared to other subtype viruses. VN/1203 virus was also found to be a potent inducer of cytokines and adhesion molecules known to regulate inflammation during acute lung injury. Deletion of the H5 hemagglutinin (HA) multibasic cleavage site did not affect virus infectivity but resulted in decreased virus replication in endothelial cells. Our results highlight remarkable tropism and infectivity of the H5N1 viruses for human pulmonary endothelial cells, resulting in the potent induction of host inflammatory responses.

First Page

667

Last Page

678

DOI

https://doi.org/10.1128/jvi.06348-11

Publication Date

1-15-2012

Department

College of Medicine

Comments

This article is available in the Journal of Virology at the following link: https://journals.asm.org/doi/full/10.1128/jvi.06348-11

Address correspondence to Terrence M. Tumpey, tft9@cdc.gov.

Copyright © 2012, American Society for Microbiology. All Rights Reserved.

Recommended Citation

Zeng, Hui, et al. "Human pulmonary microvascular endothelial cells support productive replication of highly pathogenic avian influenza viruses: possible involvement in the pathogenesis of human H5N1 virus infection." Journal of virology 86.2 (2012): 667-678.