Detection of herpes simplex virus type-1 in patients with fibrotic lung diseases.

Ismini Lasithiotaki,Nikolaos M Siafakas,George Sourvinos,Konstantinos Karagiannis,Demetrios A Spandidos,Virginia-Maria Vlahava,Katerina M Antoniou,Baochuan Lin

doi:10.1371/journal.pone.0027800

Ismini Lasithiotaki, Nikolaos M Siafakas + Show 6 more

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https://doi.org/10.1371/journal.pone.0027800

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Journal: PloS one	Publication Date: Dec 20, 2011
Citations: 84	License type: CC BY 4.0

Affiliation: University of Crete

Abstract

The current study intends to investigate i) the incidence of herpes viruses including Herpes Simplex Virus type-1 (HSV-1), Cytomegalovirus (CMV) and Human Herpes Virus -6, -7, -8 (HHV6, HHV7, HHV8) in two biological samples, bronchoalveolar lavage fluid (BALF) and lung tissue biopsy, in different forms of pulmonary fibrosis, and ii) the induction of molecular pathways involved in fibrosis by herpesvirus infection in primary cell cultures. PCR was employed for the detection of CMV, HHV6-8 and HSV-1 DNA in lung specimens (4 controls and 11 IPF specimens) and BALF pellet [6 controls and 20 fibrotic Idiopathic Intestitial Pneumonias (f-IIPs) samples: 13 idiopathic pulmonary fibrosis (IPF) and 7 nonspecific idiopathic interstitial pneumonia (NSIP)] samples. Among all herpesviruses tested, HSV-1 was detected in 1/11 (9%) specimens from IPF lung tissue and in 2/20 (10%) samples of f-IIPs BALF whereas the control group was negative. Primary cell cultures from BALF of patients with IPF and healthy controls were infected in vitro with wild-type HSV-1 virus and Real Time PCR was employed for the detection of gene transcription of specific axes implicated in lung fibrosis. Primary cell cultures were permissive to HSV-1, resulting in an upregulation of the fibrotic growth factors TGFβ1 and FGF, the angiogenetic markers SDF1a, SDF1b, VEGF, FGF and the regulators of tissue wound healing MMP9 and CCR7. Downregulation was noted for the CXCR4 and MMP2 genes, while a different response has been detected in healthy donors regarding the expression of the aforementioned markers. These results implicate for the first time the HSV-1 with Fibrotic Idiopathic Interstitial Pneumonias since the virus presented similar incidence in two different biological samples.

Highlights

Idiopathic pulmonary fibrosis (IPF) is perhaps the most pernicious and enigmatic form of a greater problem of lung fibrogenesis with no proven effective therapy other than lung transplantation and associated with a median patient survival of three years [1]
Previous studies have shown the presence of Epstein-Barr virus (EBV), Cytomegalovirus, and human herpesviruses (HHV) 7 and 8 in patients with IPF [5,6,7]
This study aimed to investigate the incidence of a wide range of herpesviruses, including HSV-1, CMV and the most recently discovered HHV6, HHV7 and HHV8, in two different biological samples, bronchoalveolar lavage fluid (BALF) and lung tissue, in different forms of pulmonary fibrosis

Summary

Introduction

Idiopathic pulmonary fibrosis (IPF) is perhaps the most pernicious and enigmatic form of a greater problem of lung fibrogenesis with no proven effective therapy other than lung transplantation and associated with a median patient survival of three years [1]. While the pathogenesis remains unclear, the spatial and temporal variance of fibrotic lesions suggests a repeated stimulus causing lung injury over the course of the disease [3]. Several studies have implicated chronic viral infection as a cause of ongoing epithelial injury in IPF and an important cofactor, either initiating or exacerbating the disease [4]. Previous studies have shown the presence of Epstein-Barr virus (EBV), Cytomegalovirus, and human herpesviruses (HHV) 7 and 8 in patients with IPF [5,6,7]. It should be noted that other studies did not find an association between herpesviral infection and IPF, and it is not clear whether these discrepancies represent geographical variation or technical differences [8,9]

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