help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on March 15, 2007, doi:10.1164/rccm.200610-1426OC

Am. J. Respir. Crit. Care Med., Volume 175, Number 11, June 2007, 1139-1150

A more recent version of this article appeared on June 1, 2007
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
200610-1426OCv1
175/11/1139    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mora, A. L
Right arrow Articles by Stecenko, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mora, A. L
Right arrow Articles by Stecenko, A.

Submitted on October 5, 2006
Accepted on March 15, 2007

Control of Virus Reactivation Arrests Pulmonary Herpesvirus Induced Fibrosis in IFN{gamma}R Deficient Mice

Ana L Mora1*, Edilson Torres-Gonzalez2, Mauricio Rojas1, Jianguo Xu2, Jeffrey Ritzenthaler3, Samuel H Speck4, Jesse Roman5, Kenneth Brigham1, and Arlene Stecenko1

1 CTRL, Emory University, Atlanta, GA, USA; Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Emory University, Atlanta, GA, USA; McKelvey Lung Transplantation, Emory University, Atlanta, GA, USA, 2 CTRL, Emory University, Atlanta, GA, USA; Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Emory University, Atlanta, GA, USA, 3 Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Emory University, Atlanta, GA, USA, 4 Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA, 5 Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Emory University, Atlanta, GA, USA; Atlanta VA Medical Center, Atlanta, GA, USA

* To whom correspondence should be addressed. E-mail: amora{at}emory.edu.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic lung disorder of unknown cause. Several studies suggest an association between EBV pulmonary infection and the development of IPF. Objective: To determine whether reduction of gammaherpesvirus reactivation from latency would alter progressive lung fibrogenesis in an animal model of virus-induced pulmonary fibrosis. Methods: IFN{gamma}R-/- mice infected intranasally with murine gammaherpesvirus 68 (MHV68)develop lung fibrosis that progresses for up to at least 180 days after initial infection. Virus replication during the chronic phase of infection was controlled by two methods: the administration of cidofovir, an antiviral effective at clearing lytic but not latent virus and by using a mutant gammaherpesvirus defective in virus reactivation from latency. Results: Ten percent of the asymptomatic MHV68 infected animals that received antiviral treatment beginning at day 45 post-infection had severe pulmonary fibrosis compared to 40% of the saline control infected animals. Absence of severe fibrosis was also observed in IFN{gamma}R-/- mice infected with the defective reactivation mutant MHV68 v-cyclin stop. Decreased fibrosis was associated with lower levels of TGF{beta},VEGF and markers macrophage alternative activation. When antiviral treatment was administered at day 60 in symptomatic animals, survival improved from 20 to 80% compared to untreated symptomatic animals but lung fibrosis persisted in 60% of the mice. Conclusions: MHV68 induced fibrosis is a result of virus lytic replication during chronic lung herpesvirus infection in mice. We speculate that antiviral therapy might help to control lung fibrosis in humans with IPF and associated herpesvirus infection.
Key words: Lung, fibrosis, herpesvirus, antiviral




This article has been cited by other articles:


Home page
 J. Virol.Home page
K. S. Lee, C. D. Cool, and L. F. van Dyk
Murine Gammaherpesvirus 68 Infection of Gamma Interferon-Deficient Mice on a BALB/c Background Results in Acute Lethal Pneumonia That Is Dependent on Specific Viral Genes
J. Virol., November 1, 2009; 83(21): 11397 - 11401.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. S. Lee, S. D. Groshong, C. D. Cool, B. K. Kleinschmidt-DeMasters, and L. F. van Dyk
Murine Gammaherpesvirus 68 Infection of IFN{gamma} Unresponsive Mice: A Small Animal Model for Gammaherpesvirus-Associated B-Cell Lymphoproliferative Disease
Cancer Res., July 1, 2009; 69(13): 5481 - 5489.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
T. R. McMillan, B. B. Moore, J. B. Weinberg, K. M. Vannella, W. B. Fields, P. J. Christensen, L. F. van Dyk, and G. B. Toews
Exacerbation of Established Pulmonary Fibrosis in a Murine Model by Gammaherpesvirus
Am. J. Respir. Crit. Care Med., April 1, 2008; 177(7): 771 - 780.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
A. G. Evans, J. M. Moser, L. T. Krug, V. Pozharskaya, A. L. Mora, and S. H. Speck
A gammaherpesvirus-secreted activator of V{beta}4+ CD8+ T cells regulates chronic infection and immunopathology
J. Exp. Med., March 17, 2008; 205(3): 669 - 684.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
A. U. Wells and C. M. Hogaboam
Update in Diffuse Parenchymal Lung Disease 2007
Am. J. Respir. Crit. Care Med., March 15, 2008; 177(6): 580 - 584.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
D. M. Center
Taking the "Idio" Out of Idiopathic Pulmonary Fibrosis: A Call to Arms
Am. J. Respir. Crit. Care Med., June 1, 2007; 175(11): 1101 - 1102.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2007 American Thoracic Society 		  Tobacco