A novel screening method detects herpesviral DNA in the idiopathic pulmonary fibrosis lung

Abstract

Background. Herpesviruses could contribute to the lung epithelial injury that initiates profibrotic responses in idiopathic pulmonary fibrosis (IPF).

Methods. We identified herpesviral DNA from IPF and control lung tissue using a multiplex PCR-and microarray-based method. Active herpesviral infection was detected by standard methods, and inflammatory cell subtypes were identified with specific antibodies. Patients that underwent lung transplantation were monitored for signs of herpesviral infection.

Results. A total of 11/12 IPF samples were positive for Epstein-Barr virus (EBV) and 10/12 for human herpesvirus 6B (HHV-6B) DNA. Control lung samples (n = 10) were negative for EBV DNA, whereas three samples were positive for HHV-6B. EBV-encoded RNA (EBER) was identified in nine IPF samples and localized mainly to lymphocytic aggregates. HHV-6B antigens were detected in mononuclear cells in IPF lung tissue. CD20+ B lymphocytic aggregates that were surrounded by CD3+ T cells were abundant in IPF lungs. CD23+ cells (activated B cells, EBV-transformed lymphoblasts, and dendritic cells) were observed in the aggregates. IPF patients had no signs of increased herpesviral activation after lung transplantation.

Conclusions. Inflammatory cells are the main source of herpesviral DNA in the human IPF lung. Diagnostic tools should be actively used to elucidate whether herpesviral infection affects the pathogenesis, progression, and/or exacerbation of IPF.

Key words::

• Herpesvirus
• interstitial fibrosis
• lymphocytes
• viral infection

Acknowledgements

We would like to thank Eriika Wasenius and Tiina Marjomaa for their skilful laboratory work.

Declaration of interest: This study has been supported by the Academy of Finland, Sigrid Jusélius Foundation, The Finnish Anti-Tuberculosis Association Foundation, Helsinki University Central Hospital (HUS-EVO), Jalmari and Rauha Ahokas Foundation, and Finska Läkaresällskapet. H. Piiparinen and A. Jääskeläinen are both former employees of Mobidiag Ltd. The other authors declare no conflicts of interest.