title: Right place, right time: the evolving role of herpesvirus infection as a "second hit" in idiopathic pulmonary fibrosis.
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.
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. jon.kropski@vanderbilt.edu
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Kropski
authors.forename: William E
authors.initials: WE
authors.lastname: Lawson
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Blackwell
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D058750:Epithelial-Mesenchymal Transition; D006566:Herpesviridae Infections / Q000150:complications* / Q000473:pathology / Q000821:virology; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000150:complications* / Q000473:pathology / Q000821:virology; D007249:Inflammation / Q000378:metabolism / Q000821:virology; D008168:Lung / Q000473:pathology / Q000821:virology; D020545:Respiratory Mucosa / Q000473:pathology / Q000821:virology
chemical_list: D016207:Cytokines