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Báo cáo y học: " Mutation of a diacidic motif in SIV-PBj Nef impairs T-cell activation and enteropathic disease"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: Mutation of a diacidic motif in SIV-PBj Nef impairs T-cell activation and enteropathic disease. | Tschulena et al. Retrovirology 2011 8 14 http www.retrovirology.eom content 8 1 14 RETR0VIR0L0GY RESEARCH Open Access Mutation of a diacidic motif in SIV-PBj Nef impairs T-cell activation and enteropathic disease I I I r I - I I I t-. - 1 f D -s I c c T -k vJfMi k IDl IV I I 1I . I k 1 f A I v D r r z t r r1 I IV II I V 1 3 It Z z h I c r k I I I f V4 Ulrich ischuiena Ralf Sanzenbacher Micnaei D MUhlebach Andre Berger Jan Munch Micnaei Schindler Frank Kirchhoff3 Roland Plesker2 Cheick Coulibaly2 Sylvia Panitz1 Steffen Prufer1 Heide MuckenTuss1 1 I I 1 Matthias Hamdorf Matthias Schweizer Klaus Cichutek Egbert Flory Abstract Background The non-pathogenic course of SIV infection in its natural host is characterized by robust viral replication in the absence of chronic immune activation and T cell proliferation. In contrast acutely lethal enteropathic SIVsmm strain PBj induces a strong immune activation and causes a severe acute and lethal disease in pig-tailed macaques after cross-species transmission. One important pathogenicity factor of the PBj virus is the PBj-Nef protein which contains a conserved diacidic motif and unusually an immunoreceptor tyrosine-based activation motif ITAM . Results Mutation of the diacidic motif in the Nef protein of the SIVsmmPBj abolishes the acute phenotype of this virus. In vitro wild-type and mutant PBj PBj-Nef202 203GG viruses replicated to similar levels in macaque PBMCs but PBj-Nef202 203GG no longer triggers ERK mitogen-activated protein MAP kinase pathway including an alteration of a Nef-associated Raf-1 ERK-2 multiprotein signaling complex. Moreover stimulation of IL-2 and downmodulation of CD4 and CD28 were impaired in the mutant virus. Pig-tailed macaques infected with PBj-Nef202 203GG did not show enteropathic complications and lethality as observed with wild-type PBj virus despite efficient replication of both viruses in vivo. Furthermore PBj-Nef202 203GG infected animals revealed reduced T-cell activation in periphery .