Differential Inflammatory response to herpes simplex virus type 1 variants in a murin model

ARTUSO MC, MATEU CG, GAZZANIGA S, PIJOL CA, WAINSTOK R, CARLUCCI MJ

Chicago

Congreso; 8th Conference of the International cytokine Society and International Society for Interferon and Cytokyne Research; 2010

Natural carrageenans are known to be potent and selective inhibitors of Herpes simplex virus. Since they are structurally similar to heparan sulfate, a cellular receptor used by the virus to enter and infect the cell, they interfere with viral adsorption. In the present work the ì/í carrageenan 1C3 was used for the obtention of viral variants. For this purpose, serial passages of HSV-1 strain F on Vero cells in the presence of increasing concentration of 1C3 were performed. Two syncytial variants: 14-1 and 17-2 were isolated. Relevant proinflammatory cytokines for an herpetic infection were analized by PCR. Murine peritoneal macrophages and RAW macrophages were infected and transcription of IL-6, TNF-á, INF-á, INF-â was studied at different time post-infection. Significantly lower levels of transcription were obtained with viral variants compared with the parental strain. These results correlate with those obtained by ELISA where aproximately 80% of reduction of IL-6 and TNF-á was observed (p <0.001 in both cases). Moreover, an inhibitory effect of IL-10 was discarded since this anti-inflammatory cytokine was not detected in supernatants. Cytokines levels in vaginal lavages from Balb/c infected intravaginally with the variants also experimented 80% reduction (p <0.01). Furthermore, studies of the inflammatory response in the lungs of infected mice with F, 14-1 and 17-2 showed differences in the cellular recruitment when assayed by immunohistochemistry and flow cytometry. Histopathology of lungs from mice infected with 17-2 showed alterations in the alveolar morphology and the presence of collagen fibers. However, those infected with F and 14-1 had a normal tissular structure but with leukocytes infiltrates in the pulmonar parenchyma. In conclusion, viral variants have an attenuated pathogenic action and evokes a reduced activation of proinflammatory cytokines. This procedure allow us to obtain strains that could have therapeutic and prophylactic perspectives.