Wirkung von Cytokinen und cytokininduzierten Proteinen auf die Replikation von Lassa-Virus und Lymphocytärem Choriomeningitis Virus

Abstract

Lassa virus is thought to be resistent to the effects of interferon (IFN). This study demonstrates that Lassa virus replication is inhibited by IFN-alpha and IFN-gamma, but not tumor necosis factor alpha (TNF-alpha), in Huh7and Vero cells. However, the effects were orders of magnitudes smaller compared to vesicular stomatitis virus. Lassa virus AV, which had causeda fulminant Lassa fever, was somewhat more inhibited than Lassa virus NL and CSF, which had been associated with less severe disease. Mostimportantly, there were no clear differences in response to IFN-alpha, IFN-gamma, and TNF-alpha between the Lassa virus strains and the strains CH-5692, Armstrong, and WE of lymphocytic choriomeningitis virus (LCMV),a related Old World arenavirus which is less pathogenic to humans than Lassa virus. Using inducible overexpression cell lines, no evidence for a role of the IFN-stimulated proteins promyelocytic leukemia protein(PML) and Sp100 in the IFN-mediated inhibition of Lassa virus and LCMV replication was found. This and the previous finding that PML knockout facilitates LCMV replication in vitro and in vivo (M. Djavani et al., J.Virol. 75:6204-6208; W. V. Bonilla et al., J. Virol. 76:3810-3818) would fit with the hypothesis that PML is a mediator in the antiviral pathway rather than a direct effector protein. In conclusion, the data show thatLassa virus is susceptible to IFN-alpha and IFN-gamma which is of relevance for the design of antiviral strategies against Lassa fever, aiming at enhancing the IFN response. In contrast to influenza A viruses (S. H.Seo et al., Nat. Med. 8:950-954), there appears to be no correlation between the pathogenicity of Old World arenaviruses and their sensitivity to IFN.