Viruses in Idiopathic Pulmonary Fibrosis. Etiology and Exacerbation

Ann Am Thorac Soc. 2015 Nov;12 Suppl 2(Suppl 2):S186-92. doi: 10.1513/AnnalsATS.201502-088AW.


Viral infections are important contributors to exacerbation of asthma and chronic obstructive pulmonary disease; however, the role of viruses in the pathogenesis of idiopathic pulmonary fibrosis (IPF) is less clear. This likely reflects that fact that IPF acute exacerbations are defined clinically as "noninfectious," and little attention has been paid to the outcomes of patients with IPF with diagnosed infections. However, accumulating evidence suggests that infections (both bacterial and viral) may influence disease outcomes either as exacerbating agents or initiators of disease. Support for a viral role in disease initiation comes from studies demonstrating the presence of herpesviral DNA and epithelial cell stress in the lungs of asymptomatic relatives at risk for developing familial IPF. In addition, the number of studies that can associate viral (especially herpesviral) signatures in the lung with the development of IPF is steadily growing, and activated leukocyte signatures in patients with IPF provide further support for infectious processes driving IPF progression. Animal modeling has been used to better understand how a gamma herpesvirus infection can modulate the pathogenesis of lung fibrosis and has demonstrated that preceding infections appear to reprogram lung epithelial cells during latency to produce profibrotic factors, making the lung more susceptible to subsequent fibrotic insult, whereas exacerbations of existing fibrosis, or infections in susceptible hosts, involve active viral replication and are influenced by antiviral therapy. In addition, there is new evidence that bacterial burden in the lungs of patients with IPF may predict a poor prognosis.

Keywords: aging; fibroblast; herpesvirus; immunity; lung.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Acute Disease
  • Aging*
  • Animals
  • Bone Marrow Transplantation / methods
  • Disease Models, Animal
  • Disease Progression
  • Epithelial Cells / virology
  • Herpesviridae / genetics
  • Herpesviridae Infections / complications
  • Humans
  • Idiopathic Pulmonary Fibrosis / therapy
  • Idiopathic Pulmonary Fibrosis / virology*
  • Lung / virology*
  • Mice
  • Virus Diseases / complications*