Effect of Downstream Sequence on the Cleavage of Envelop Protein 1 Signal Sequence in Hepatitis C Virus.

The RNA genome of hepatitis C virus encodes a polyprotein of 3 000 amino acids, which is processed into 10 viral proteins by proteases provided by host cells and virus itself. Multiple precursors are produced due to inefficient processing. Here, the study of E1 signal sequence (C/E1 site) processing in eukaryotic vaccinia virus/T7 system is reported. Differently truncated HCV structural proteins were expressed in this system. It was found that the efficient cleavage of E1 signal sequence was affected by downstream envelope protein sequences. When the lacZ gene encoding a product with similar size was engineered downstream to the E1 signal sequence, the inefficient cleavage of signal sequence was also observed, suggesting that the effect of downstream sequence on the cleavage was due to the presence of the envelop protein sequences. Computer-aided analysis clearly showed that E1 signal sequences was a typical signal sequence. The influence of downstream sequences to signal sequence cleavage demonstrated here was uncommon. To date, similar observations were only reported for the processing of IL-12 signal sequence and the C/prM site of flavivirus. As both flavivirus and HCV are classified into the same Flaviviridae family, this downstream-sequence-related cleavage of signal sequence worths further studying.