Published: Nov 19, 2013
By Michael Smith
Full Story: http://www.medpagetoday.com/Pulmonology/GeneralPulmonary/42997
Action Points
- Note that this small case-control study demonstrated that herpesvirus saimiri was present in tissue samples of all patients with idiopathic pulmonary fibrosis but no control patients.
- Be aware that larger studies in broader populations will be necessary to confirm these findings.
Idiopathic pulmonary fibrosis (IPF), a fatal progressive lung disease, might be caused by a virus, researchers reported.
Evidence of the pathogen, herpesvirus saimiri, was found in all tissue samples from a cohort of patients with IPF, but in none of those from patients with fibrosis with a known cause, according to Gerard Nuovo, MD, of Ohio State University Comprehensive Cancer Center in Marion, and colleagues.
The finding might be useful in diagnosing IPF, a disease for which there is currently no diagnostic test, Nuovo and colleagues reported online in Modern Pathology.
And interventions aimed at stopping the proliferation of herpesvirus saimiri might stabilize IPF, which is typically fatal within 2 years of diagnosis, the researchers argued.
IPF affects about 200,000 in the U.S., which is about a fifth of those suffering from all forms of pulmonary fibrosis.
“Discovering the origin of IPF gives us hope that both diagnostics and treatments will be developed to help patients survive and live with this devastating illness,” Nuovo said in a statement.
Herpesvirus saimiri is a member of the gamma-herpesvirus family, some of whose members are known to cause pulmonary fibrosis in animals. The virus does not cause disease in its natural host, the squirrel monkey, but causes fatal T-cell lymphomas and leukemias in New World monkeys, the researchers noted.
Importantly, a productive infection with herpesvirus saimiri is associated with viral expression of four “pirated” mammalian proteins — interleukin-17, cyclin D, thymidylate synthase, and dihydrofolate reductase. Other gamma-herpesviruses express some but not all of the four, Nuovo and colleagues noted.
For this study, Nuovo and colleagues first tried to see if IPF was associated with any herpesvirus, including such pathogens as Epstein-Barr virus, cytomegalovirus, and herpes simplex viruses.
They screened tissue from 13 cases of IPF and found that all were positive for herpesvirus saimiri DNA, but none was positive for DNA from the other viruses.
That finding led them to expand the study to 21 cases of IPF and 21 controls — cases of pulmonary fibrosis of known etiology, including seven cases of fibrosis-related adenocarcinoma of the lung, five cases of lung fibrosis associated with emphysema, and nine cases of interstitial pneumonitis and fibrosis with a known viral cause.
In the expanded study, analysis blinded to the diagnosis showed that again all of the IPF cases were positive for herpesvirus saimiri DNA, but not one of the other cases, Nuovo and colleagues reported.
The four pirated proteins — cyclin D, thymidylate synthase, dihydrofolate reductase, and interleukin-17 — were strongly expressed in regenerating epithelial cells of the IPF cases, but not in the epithelia of the controls, they found.
Real-time polymerase chain reaction testing showed that the cyclin D RNA in active IPF was viral, not human, in nature.
And when the researchers cloned and sequenced part of the genome corresponding to the herpesvirus saimiri DNA polymerase gene, using an IPF tissue sample, it was an exact match for the published viral sequence.
“While the sample size is small,” Nuovo said, “there are multiple data points that support our findings that herpesvirus saimiri infection may be the cause of IPF.”
The work was supported by the Lewis Foundation. The authors declared no conflicts, although one of the authors is employed by Enzo Biochem, which is applying for a patent based on the findings.
Primary source: Modern Pathology