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

• Published in: PloS one 2011-12, Vol.6 (12), p.e27800-e27800
• Main Authors: Lasithiotaki, Ismini, Antoniou, Katerina M, Vlahava, Virginia-Maria, Karagiannis, Konstantinos, Spandidos, Demetrios A, Siafakas, Nikolaos M, Sourvinos, George
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; AIDS; Alveoli; Biological properties; Biological samples; Biology; Biopsy; Biotechnology; Bronchoalveolar lavage; Bronchoalveolar Lavage Fluid - virology; Bronchus; Care and treatment; CC chemokine receptors; CCR7 protein; Cell culture; Chemokines; CXCR4 protein; Cytokines; Cytomegalovirus; Cytomegalovirus - isolation & purification; Deoxyribonucleic acid; DNA; Fibroblast growth factor; Fibroblast growth factors; Fibrosis; Gelatinase A; Gelatinase B; Gene expression; Gene Expression Regulation; Genes; Growth factors; Health aspects; Herpes simplex; Herpes simplex virus; Herpes viruses; Herpesvirus 1, Human - isolation & purification; Herpesvirus 1, Human - pathogenicity; HIV; Human immunodeficiency virus; Humans; Hypotheses; Immunity, Innate; Incidence; Infection; Infections; Infertility; Kinases; Laboratories; Lung - pathology; Lung - virology; Lung cancer; Lung diseases; Markers; Medical schools; Medicine; Pathogenesis; Patients; Pneumonia; Polymerase chain reaction; Pulmonary fibrosis; Pulmonary Fibrosis - genetics; Pulmonary Fibrosis - immunology; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - virology; Regulators; Sarcoidosis; Studies; Transcription; Transcription (Genetics); Transforming growth factor-b1; Vascular endothelial growth factor; Viral infections; Virology; Viruses; Wound Healing
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0027800

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.