Viruses evade the immune system through type I interferon-mediated STAT2-dependent, but STAT1-independent, signaling

Speaker: 吳育欣

Time: 15:00-16:00 Apr. 13, 2005

Place: Room 601

Commentator: 陳舜華

Abstract:

     Type I IFNs, a major component of the innate immune system, are induced at early period after viral infection. They have multiple functions, such as protection of lymphocytes from apoptosis, suppression of cell proliferation, up-regulation of MHC class I molecules and modulation of immunoglobulins production. Type I IFNs and their receptors activate tyrosine kinases -- Jak 1 and Tyk 2 – and then phosphorylate the signal transducer and activators of transcription (STAT) 1 and STAT2 to form a STAT1/STAT2 heterodimer. Previous studies in virus-induced type I IFN’s role in dendritic cell (DC) development are often conflicting and thus unclear. DCs potently stimulate naïve T cells to develop adaptive immune responses, therefore they are targeted by multiple viruses. The authors demonstrated previously that an immunosuppressive strain of lymphocytic choriomeningitis virus (LCMV) clone 13 aborted the function of DCs by downregulation of costimulatory molecules and inhibiting DC expansion. In this study, they found that Measles virus (MV) inhibits the development of DCs from hematopoietic bone marrow cells via type I IFN pathway. Furthermore they found that MV-induced suppression of DC development  dependents on STAT2 but is independent of STAT1 signaling pathway. The same results were found in the experiments using LCMV clone 13. These observations contradict the conventional concept that type I IFN response requires both STAT1 and STAT2. The IFN/STAT2-mediated inhibition of DC development is an additional way for viruses to evade host adaptive immune responses and/or to establish persistence.

References:

1.     Biron, C.A. Interferons a and b as immune regulators-a new look. Immunity 2001 14, 661-664

2.     Ito, T. et al. Differential regulation o human blood dendritic cell subsets by IFNs. J. Immunol. 2001 166, 2961-2969

3.     Hahm, B. et al. Viruses evade the immune system through type I interferon-mediated STAT2-dependent, but STAT1-independent, signaling. Immunity 2005 22, 247-257