Latent herpesvirus infection augments experimental pulmonary fibrosis

Academic Article

Abstract

  • Rationale: No effective treatment exists for idiopathic pulmonary fibrosis, and its pathogenesis remains unclear. Accumulating evidence implicates herpesviruses as cofactors (either initiating exacerbating agents) of fibrotic lung disease, but a role for latent herpesvirus infection has not been studied. Objectives: To develop a murine model to determine whether latent herpesvirus infection can augment fibrotic responses and to gain insight into potential mechanisms of enhanced fibrogenesis. Methods: Mice were infected with murine γherpesvirus 14 to 70 days before a fibrotic challenge with fluorescein isothiocyanate or bleomycin so that the virus was latent at the time of fibrotic challenge. Measurements were made after viral infection alone or after the establishment of fibrosis. Measurements and Main Results: γHerpesvirus is latent by 14 days post infection, and infection 14 to 70 days before fibrotic challenge augmented fibrosis. Fibrotic augmentation was not dependent on reactivation of the latent virus to a lytic state. Total cell numbers and fibrocyte numberswere increased in the lungs latently infected mice administered fibrotic challenge compared with mock-infected mice that received fibrotic challenge. Latent infection up-regulates expression of proinflammatory chemokines, transforming growth factor-β1, and cysteinyl leukotrienes in alveolar epithelial cells. Conclusions: Latent γherpesvirus infection augments subsequent fibrotic responses inmice. Enhanced fibrosis is associated with the induction of profibrotic factors and the recruitment of fibrocytes. Our data complement existing human and animal data supporting the hypothesis that γherpesviruses can serve as initiating cofactors in the pathogenesis of pulmonary fibrosis.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Vannella KM; Luckhardt TR; Wilke CA; Van Dyk LF; Toews GB; Moore BB
  • Start Page

  • 465
  • End Page

  • 477
  • Volume

  • 181
  • Issue

  • 5