CCL3 and viral chemokine-binding protein gg modulate pulmonary inflammation and virus replication during equine herpesvirus 1 infection.
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.
Van de Walle
Gerlinde R
GR
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Sakamoto
Kaori
K
Osterrieder
Nikolaus
N
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism*; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004861:Herpesvirus 1, Equid / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D011024:Pneumonia, Viral / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019562:Viral Load; D014779:Virus Replication
D000914:Antibodies, Viral; D054405:Chemokine CCL3; D014759:Viral Envelope Proteins; C083103:glycoprotein G, Equid herpesvirus 1