Right place, right time: the evolving role of herpesvirus infection as a "second hit" in idiopathic pulmonary fibrosis

Am J Physiol Lung Cell Mol Physiol. 2012 Mar 1;302(5):L441-4. doi: 10.1152/ajplung.00335.2011. Epub 2011 Dec 16.

Abstract

Over the course of the past decade, increasing evidence has implicated alveolar epithelial cell injury and dysfunction in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Genetic factors, cigarette smoking, and other environmental exposures have been identified as potential factors leading to a population of vulnerable alveolar epithelial cells. In addition, molecular techniques have demonstrated herpesviruses are commonly detectable in the lungs of patients with IPF, raising suspicion that, in the setting of a vulnerable alveolar epithelium, lytic (or latent) herpesvirus infection may act as a "second hit" leading to the development of pulmonary fibrosis. Intriguingly, in vivo modeling has shown that herpesvirus infection induces or worsens lung fibrosis when combined with immunodeficiency or other injurious stimuli. Here, we discuss potential mechanisms through which herpesvirus infection may contribute to the pathogenesis of IPF. Ultimately, antiviral therapy may hold promise for halting the progression of this deadly disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Endoplasmic Reticulum Stress
  • Epithelial-Mesenchymal Transition
  • Herpesviridae Infections / complications*
  • Herpesviridae Infections / pathology
  • Herpesviridae Infections / virology
  • Humans
  • Idiopathic Pulmonary Fibrosis / complications*
  • Idiopathic Pulmonary Fibrosis / pathology
  • Idiopathic Pulmonary Fibrosis / virology
  • Inflammation / metabolism
  • Inflammation / virology
  • Lung / pathology
  • Lung / virology
  • Respiratory Mucosa / pathology
  • Respiratory Mucosa / virology

Substances

  • Cytokines