Rosalinda Harnack

Washington University in St. Louis

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Ahmed Sabbah

The University of Texas Health Science Center at San Antonio

Santanu Bose

Washington State University

Yan Xiang

Affiliated Hospital of North Sichuan Medical College

Te Hung Chang

Washington University in St. Louis

Swetha Kota

The University of Texas at Austin

Peter H. Dube

Boehringer Ingelheim (United States)

Bandana Chatterjee

The University of Texas Health Science Center at San Antonio

Kaoru Tominaga

Jichi Medical University

T. Arthur Chang

The University of Texas Health Science Center at San Antonio

Ibtissam Echchgadda

59th Medical Wing

Cooperative Institutions

The University of Texas Health Science Center at San Antonio

The University of Texas Health Science Center at Houston

Feinstein Institute for Medical Research

Washington University in St. Louis

The University of Texas at San Antonio

Central South University

Audie L. Murphy Memorial VA Hospital

The University of Texas System

The University of Texas at Austin

Durham VA Health Care System

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Role of Human β-Defensin-2 during Tumor Necrosis Factor-α/NF-κB-mediated Innate Antiviral Response against Human Respiratory Syncytial Virus

Journal of Biological Chemistry (2008)

Srikanth Kota Ahmed Sabbah Te Hung Chang Rosalinda Harnack Yan Xiang

Human respiratory syncytial virus (RSV) constitutes a highly pathogenic virus that infects lung epithelial cells to cause a wide spectrum of respiratory diseases. Our recent studies have revealed the existence of an interferon-alpha/beta-independent, innate antiviral response against RSV that was dependent on activation of NF-kappaB. We demonstrated that NF-kappaB inducing pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF) confers potent antiviral function against RSV in an NF-kappaB-dependent fashion, independent of interferon-alpha/beta. During our efforts to study this pathway, we identified HBD2 (human beta-defensin-2), a soluble secreted cationic protein as an antiviral factor induced during NF-kappaB-dependent innate antiviral activity in human lung epithelial cells. Our results demonstrated that HBD2 is induced by TNF and RSV in an NF-kappaB-dependent manner. Induction of HBD2 in infected cells was mediated by the paracrine/autocrine action of TNF produced upon RSV infection. HBD2 plays a critical role during host defense, because purified HBD2 drastically inhibited RSV infection. We also show that the antiviral mechanism of HBD2 involves blocking of viral cellular entry possibly because of destabilization/disintegration of the viral envelope. The important role of HBD2 in the innate response was also evident from loss of antiviral activity of TNF upon HBD2 silencing by short interfering RNA. The in vivo physiological relevance of HBD2 in host defense was apparent from induction of murine beta-defensin-4 (murine counterpart of HBD2) in lung tissues of RSV-infected mice. Thus, HBD2 functions as an antiviral molecule during NF-kappaB-dependent innate antiviral immunity mediated by the autocrine/paracrine action of TNF.

Beta defensin

10.1074/jbc.m710415200

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Citations (151)

Erratum: Corrigendum: Activation of innate immune antiviral responses by Nod2

Nature Immunology (2010)

Ahmed Sabbah Te Hung Chang Rosalinda Harnack Victoria Centonze Frohlich Kaoru Tominaga

Nat

10.1038/ni1010-969b

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Citations (3)

Erratum: Anticancer oncolytic activity of respiratory syncytial virus