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Journal of Virology, February 2008, p. 1714-1722, Vol. 82, No. 4
0022-538X/08/$08.00+0     doi:10.1128/JVI.02137-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

CCL3 and Viral Chemokine-Binding Protein gG Modulate Pulmonary Inflammation and Virus Replication during Equine Herpesvirus 1 Infection{triangledown}

Gerlinde R. Van de Walle, Kaori Sakamoto, and Nikolaus Osterrieder*

Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853

Received 28 September 2007/ Accepted 28 November 2007

CCL3 is a proinflammatory chemokine that mediates many of the cellular changes occurring in pulmonary disease. Here, CCL3–/– mice were used to investigate the role of this chemokine during respiratory herpesvirus infection. Compared to wild-type mice, CCL3–/– mice infected with the alphaherpesvirus equine herpesvirus 1 (EHV-1) displayed reduced body weight loss but had higher pulmonary viral loads. Lungs from infected CCL3–/– mice suffered a milder interstitial pneumonia, and fewer immune cells were recovered from the pulmonary airways after infection. We could also demonstrate that herpesvirus-encoded chemokine-binding glycoprotein G (gG) was capable of inhibiting the chemotactic functions of CCL3. This CCL3-mediated chemotaxis, however, was restored in the presence of gG-specific antibodies, which puts into question the advertised use of gG deletion mutants as marker vaccines. In summary, we concluded that CCL3 is a major player in controlling herpesvirus replication in the target organ, the lung, and does so by evoking a strong inflammatory response. The immunomodulatory activity of CCL3 is balanced by the expression of viral gG, whose chemokine-binding activity is mitigated in secondary infections by the production of anti-gG antibodies.


* Corresponding author. Mailing address: Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853. Phone: (607) 253-4045. Fax: (607) 253-3384. E-mail: no34{at}cornell.edu

{triangledown} Published ahead of print on 12 December 2007.


Journal of Virology, February 2008, p. 1714-1722, Vol. 82, No. 4
0022-538X/08/$08.00+0     doi:10.1128/JVI.02137-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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