Idiopathic pulmonary fibrosis is strongly associated with productive infection by herpesvirus saimiri.
Idiopathic pulmonary fibrosis is a fatal disease without effective therapy or diagnostic test. To investigate a potential role for γ-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 γ-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 γ-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 γ-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.
1] The Ohio State University (OSU) at Marion, Marion, OH, USA [2] OSU Computer Science and Engineering, Marion, OH, USA [3] OSU Innovation Group for the Study of Complexity in Human, Natural, and Engineered Systems, Marion, OH, USA.
Virginia A
VA
Folcik
Satellite Laboratory, Ohio State Univ Comprehensive Cancer Center, Powell, Columbus, OH, USA.
Michela
M
Garofalo
Enzo Biochem, Farmingdale, NY, USA.
Jack
J
Coleman
Enzo Biochem, Farmingdale, NY, USA.
James J
JJ
Donegan
Enzo Biochem, Farmingdale, NY, USA.
Elazar
E
Rabbani
Medical College of Wisconsin, Milwaukee, WI, USA.
Saul
S
Suster
OSU Wexner Medical Center, Columbus, OH, USA.
Allison
A
Nuovo
Weill Cornell Medical Center, New York, NY, USA.
Cynthia M
CM
Magro
Satellite Laboratory, Ohio State Univ Comprehensive Cancer Center, Powell, Columbus, OH, USA.
Gianpiero
G
Di Leva
1] Satellite Laboratory, Ohio State Univ Comprehensive Cancer Center, Powell, Columbus, OH, USA [2] Phylogeny Inc, Powell, OH, USA.
Gerard J
GJ
Nuovo
D000368:Aged; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D006566:Herpesviridae Infections / Q000150:complications*; D006567:Herpesvirus 2, Saimiriine; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000821:virology*; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004279:DNA, Viral