A novel screening method detects herpesviral DNA in the idiopathic pulmonary fibrosis lung.
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.
Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland. ville.pulkkinen@helsinki.fi
Ville
V
Pulkkinen
Kaisa
K
Salmenkivi
Vuokko L
VL
Kinnula
Eva
E
Sutinen
Maija
M
Halme
Ulla
U
Hodgson
Juho
J
Lehto
Anne
A
Jääskeläinen
Heli
H
Piiparinen
Juha
J
Kere
Irmeli
I
Lautenschlager
Maija
M
Lappalainen
Marjukka
M
Myllärniemi
D000328:Adult; D000368:Aged; D004279:DNA, Viral / Q000032:analysis; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000473:pathology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D015654:Herpesvirus 6, Human / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000821:virology*; D008168:Lung / Q000821:virology*; D016040:Lung Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D019349:Roseolovirus Infections / Q000150:complications* / Q000473:pathology
D004279:DNA, Viral