Transient transfection of mouse fibroblasts with type I interferon transgenes provides various degrees of protection against herpes simplex virus infection.

Type I interferons (IFN) constitute one of the initial and most potent components of the innate immune response against viral infections. While there is only one IFN-beta gene, there are several IFN-alpha genes whose products act through the same receptor calling into question the role of these gene products against viral infection. The focus of the present study was to compare the anti-viral state of cells transiently transfected with different murine type I IFN transgenes including IFN-alpha1, -alpha4, -alpha5, -alpha6, -alpha9, and IFN-beta. Transfected cells produced biologically active IFN ranging from 6 to 46 units/ml. L929 and 3T12.3 cells transfected with the IFN-beta transgene consistently showed a 2-4 fold reduction in herpes simplex virus type 1 (HSV-1) and HSV-2 viral titers compared with cells transfected with the IFN-alpha transgenes which were much less consistent based on HSV species and cell type. Parallel with the reduction in viral titers, cells transfected with the IFN-beta transgene showed the complete absence or significant reduction in viral immediate early, early, and late gene expression. Collectively, the results suggest that the IFN-beta transgene is superior to IFN-alpha transgenes against HSV infection in vitro in part due to a reduction in viral gene expression. These results indicate events downstream of the type I IFN receptor distinguish between the subtypes of IFN-alpha species relative to the activation of genes ultimately responsible for the establishment of the anti-HSV state.

Characterisation of murine cytomegalovirus myocarditis: cellular infiltration of the heart and virus persistence.

Myocarditis triggered by a viral infection has integral viral and immunological aspects associated with the pathogenesis of disease. The present study was performed to analyse the cellular inflammatory response in the heart and cytomegalovirus replication during the development of myocarditis in vivo. We examined murine cytomegalovirus in an animal model of myocarditis using both susceptible BALB/c and resistant C57BL/6 mice. The heart infiltrating cells of BALB/c mice were found to comprise predominantly CD8+ T cells, with other cells of the CD4+ T cell, macrophage, B cell and neutrophil phenotype. Infectious MCMV titres in the heart were low and replicative virus could not be isolated beyond the first week post-infection (p.i.). Direct viral lysis of myocytes in vitro and apoptosis of cardiac cells in vivo was observed. Furthermore, viral DNA was detected in the heart of both mouse strains throughout the development of chronic disease. Viral gB RNA was detected during the first 35 days p.i. However, viral transcript for ie1 RNA but not gB RNA was found in the heart during the late stage of disease, suggesting latent viral infection of the heart. Our findings suggest that maintenance of the chronic phase of myocarditis involving post-viral immunological responses can occur in the presence of little infectious virus replication in the heart.