Idiopathic pulmonary fibrosis is strongly
associated with productive infection by
herpesvirus saimiri

Folcik, V; Garofalo, M; Coleman, J; Donegan, J; Rabbani, E; Suster, S; Nuovo, A; Magro, C; Di Leva, Gianpiero; Nuovo, G

Abstract

Idiopathic pulmonary fibrosis is a fatal disease without effective therapy or diagnostic test. To investigate a
potential role for c�herpesviruses in this disease, 21 paraffin-embedded lung biopsies from patients diagnosed
with idiopathic pulmonary fibrosis and 21 lung biopsies from age-matched controls with pulmonary fibrosis of
known etiology were examined for a series of c�herpesviruses’ DNA/RNA and related proteins using in situ
hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR)-based methods. We detected four
proteins known to be in the genome of several c�herpesviruses (cyclin D, thymidylate synthase, dihydrofolate
reductase, and interleukin-17) that were strongly co-expressed in the regenerating epithelial cells of each of the
21 idiopathic pulmonary fibrosis cases and not in the benign epithelia of the controls. Among the c�
herpesviruses, only herpesvirus saimiri expresses all four of these ‘pirated’ mammalian proteins. We found
herpesvirus saimiri DNA in the regenerating epithelial cells of 21/21 idiopathic pulmonary fibrosis cases using
four separate probe sets but not in the 21 controls. RT-PCR showed that the source of the cyclin D RNA in active
idiopathic pulmonary fibrosis was herpesvirus saimiri and not human. We cloned and sequenced part of
genome corresponding to the DNA polymerase herpesvirus saimiri gene from an idiopathic pulmonary fibrosis
sample and it matched 100% with the published viral sequence. These data are consistent with idiopathic
pulmonary fibrosis representing herpesvirus saimiri-induced pulmonary fibrosis. Thus, treatment directed
against viral proliferation and/or viral-associated proteins may halt disease progression. Further, demonstration
of the viral nucleic acids or proteins may help diagnose the disease.

Citation

herpesvirus saimiri. Modern Pathology, 27, 851-862. https://doi.org/10.1038/modpathol.2013.198

• Journal Article Type: Article
• Acceptance Date: Sep 22, 2013
• Online Publication Date: Nov 15, 2013
• Publication Date: Nov 15, 2013
• Deposit Date: Jul 26, 2016
• Publicly Available Date: Jul 26, 2016
• Journal: Modern Pathology
• Print ISSN: 0893-3952
• Electronic ISSN: 1530-0285
• Publisher: Nature Publishing Group
• Volume: 27
• Pages: 851-862
• DOI: https://doi.org/10.1038/modpathol.2013.198
• Publisher URL: http://dx.doi.org/10.1038/modpathol.2013.198
• Related Public URLs: http://www.nature.com/modpathol/index.html
• Additional Information: Funders : Lewis Foundation