Evidence That Respiratory Tract Is Major Reservoir for Epstein-Barr Virus

Lung, Maria Li; So, S. Y.; Chan, Kwok‐Hung; Lam, Wah‐Kit; Lam, Wai Pang; Ng, Mun Hon

doi:10.1016/s0140-6736(85)91671-x

Cited by 75 publications

(50 citation statements)

References 30 publications

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“…This study explores links between IPF and herpesviruses [ (46,51,78,89) (9)] contains human IL-13 promoter sequences directing expression of firefly luciferase. For each luciferase reporter construct, the ratio of firefly luciferase to renilla luciferase in the presence of empty vector (pRCCMV) was normalized to 1.…”

Section: Discussionmentioning

confidence: 99%

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Modulation of lung inflammation by the Epstein-Barr virus protein Zta

Guenther¹,

Cameron²,

Nguyen³

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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Several studies have implicated gamma-herpesviruses, particularly Epstein-Barr virus (EBV), in the progression of idiopathic pulmonary fibrosis. The data presented here examine the possible role that EBV plays in the potentiation of this disease by evaluating the pulmonary response to expression of the EBV lytic transactivator protein Zta. Expression of Zta in the lungs of mice via adenovirus-mediated delivery (Adv-Zta) produced profibrogenic inflammation that appeared most pronounced by day 7 postexposure. Relative to mice exposed to control GFP-expressing adenovirus (Adv-GFP), mice exposed to Adv-Zta displayed evidence of lung injury and a large increase in inflammatory cells, predominantly neutrophils, recovered by bronchoalveolar lavage (BAL). Cytokine and mRNA profiling of the BAL fluid and cells recovered from Adv-Zta-treated mice revealed a Th2 and Th17 bias. mRNA profiles from Adv-Zta-infected lung epithelial cells revealed consistent induction of mRNAs encoding Th2 cytokines. Coexpression in transient assays of wild-type Zta, but not a DNA-binding-defective mutant Zta, activated expression of the IL-13 promoter in lung epithelial cells, and detection of IL-13 in Adv-Zta-treated mice correlated with expression of Zta. Induction of Th2 cytokines in Zta-expressing mice corresponded with alternative activation of macrophages. In cell culture and in mice, Zta repressed lung epithelial cell markers. Despite the profibrogenic character at day 7, the inflammation resolves by 28 days postexposure to Adv-Zta without evidence of fibrosis. These observations indicate that the EBV lytic transactivator protein Zta displays activity consistent with a pathogenic role in pulmonary fibrosis associated with herpesvirus infection.

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Section: Discussionmentioning

confidence: 99%

“…EBV can replicate in the lower respiratory tract (46), and expression of Zta occurs during lytic replication of EBV (68). Controlling EBV replication has stabilized lung function in a limited number of IPF patients (78).…”

Section: Discussionmentioning

confidence: 99%

Modulation of lung inflammation by the Epstein-Barr virus protein Zta

Guenther¹,

Cameron²,

Nguyen³

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…EBV has been identified in the lower airways and is seen within exfoliated epithelial cells using in situ hybridisation [13]. EBV has also been frequently found in the lungs in pulmonary fibrosis [14].…”

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confidence: 99%

High levels of Epstein–Barr virus in COPD

McManus¹,

Marley²,

Baxter³

et al. 2008

Eur Respir J

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Latent viral infection has been implicated in the pathophysiology of chronic obstructive pulmonary disease (COPD). Epstein-Barr virus (EBV) is known to be important in pulmonary fibrosis. The current authors hypothesised that EBV is associated with the pathogenesis of COPD.Sputum samples were collected from patients both during exacerbations of COPD and when stable. A control group of smokers who did not have airways obstruction also had their sputum examined. The presence of EBV DNA was established and quantified using a real-time nucleic acid amplification assay.A total of 136 patients with COPD were recruited during an acute exacerbation and a total of 68 when stable. EBV was detected in 65 (48%) exacerbation cases and 31 (46%) stable patients. In the comparison group of 16 nonobstructed smokers, EBV was demonstrated in only one (6%) case. Risk of COPD in patients with EBV and who are smokers confers an odds ratio of 12.6.Epstein-Barr virus DNA is more frequently identified in the respiratory tract of chronic obstructive pulmonary disease patients in comparison with unaffected smokers. It is present both during exacerbation and when stable, suggesting that infection is persistent. Smokers who do not develop chronic obstructive pulmonary disease rarely have Epstein-Barr virus in their sputum. This finding may be of importance in the pathogenesis of chronic obstructive pulmonary disease.

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“…EBERs are expressed during the latent phase of EBV infection [16]. As the respiratory tract is known to be a major reservoir for EBV, the question remains whether EBV is just a "passenger" or a pathogen, when localized in lung tissue [17]. However, atypical lymphocytes hybridized with a probe specific for internal repeat region 1 (BamHI W) of EBV indicate productive infection [18].…”

Section: Discussionmentioning

confidence: 99%

Chronic interstitial lung disease due to Epstein-Barr virus infection in two infants

Pfleger¹,

Eber²,

Popper³

et al. 2000

Eur Respir J

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This case study reports on two infants, 5 and 6 months of age, respectively, with chronic interstitial lung disease who presented with failure to thrive, tachypnoea, rales and mild hypoxaemia.Epstein-Barr virus (EBV) was detected by in situ hybridization in lung biopsy specimens and by EBV-deoxyribonucleic acid-polymerase chain reaction (PCR) in bronchoalveolar lavage (BAL) fluid in one patient and by in situ hybridization and PCR analysis in BAL fluid in the second patient. There was serological evidence of immunoglobulin G antibodies to EBV capsid antigen by indirect immunofluorescence in both patients.After 7 months of respiratory symptoms one patient was successfully treated with a 10 day course of intravenous ganciclovir followed by oral acyclovir for 20 days. The other patient became symptom free after 3.5 months of respiratory symptoms, without any specific antiviral medication. During a follow-up of 2 and 1.5 yrs, respectively, both infants remained symptom free and showed normal physical development. Eur Respir J 2000; 15: 803±806.

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Evidence That Respiratory Tract Is Major Reservoir for Epstein-Barr Virus

Cited by 75 publications

References 30 publications

Modulation of lung inflammation by the Epstein-Barr virus protein Zta

Modulation of lung inflammation by the Epstein-Barr virus protein Zta

High levels of Epstein–Barr virus in COPD

Chronic interstitial lung disease due to Epstein-Barr virus infection in two infants

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