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A negative feedback modulator of antigen processing evolved from a frameshift in the cowpox virus genome.

PLoS Pathog. 2014; 
Lin J, Eggensperger S, Hank S, Wycisk AI, Wieneke R, Mayerhofer PU, Tampé R.
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Codon Optimization Materials and Methods Cloning, constructs and recombinant viruses CPXV012 (Gene ID: 1485887) with an N-terminal His10-flag tag (flagCPXV012) was codon optimized for expression in mammalian and insect cells and synthesized de novo (GenScript, Piscataway, NJ, USA). Get A Quote

摘要

Coevolution of viruses and their hosts represents a dynamic molecular battle between the immune system and viral factors that mediate immune evasion. After the abandonment of smallpox vaccination, cowpox virus infections are an emerging zoonotic health threat, especially for immunocompromised patients. Here we delineate the mechanistic basis of how cowpox viral CPXV012 interferes with MHC class I antigen processing. This type II membrane protein inhibits the coreTAP complex at the step after peptide binding and peptide-induced conformational change, in blocking ATP binding and hydrolysis. Distinct from other immune evasion mechanisms, TAP inhibition is mediated by a short ER-lumenal fragment of CPXV012, which r... More

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