Gammaherpesviruses and pulmonary fibrosis: evidence from humans, horses, and rodents

Progressive lung fibrosis in humans, typified by idiopathic pulmonary fibrosis (IPF), is a serious cause of morbidity and mortality in people. Similar diseases have been described in dogs, cats, and horses. The cause and pathogenesis of such diseases in all species is poorly understood. There is growing evidence in human medicine that IPF is a manifestation of abnormal wound repair in response to epithelial injury. Because viruses can contribute to epithelial injury, there is increasing interest in a possible role of viruses, particularly gammaherpesviruses, in the pathogenesis of pulmonary fibrosis. This review provides background information on progressive fibrosing lung disease in human and veterinary medicine and summarizes the evidence for an association between gammaherpesvirus infection and pulmonary fibrosis, especially Epstein-Barr virus in human pulmonary fibrosis, and equine herpesvirus 5 in equine multinodular pulmonary fibrosis. Data derived from experimental lung infection in mice with the gammaherpesvirus murine herpesvirus are presented, emphasizing the host and viral factors that may contribute to lung fibrosis. The experimental data are considered in the context of the pathogenesis of naturally occurring pulmonary fibrosis in humans and horses.