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Internal initiation sites of de novo RNA synthesis within the hepatitis C virus polypyrimidine tract
Authors:Pellerin Charles  Lefebvre Sylvain  Little Michael J  McKercher Ginette  Lamarre Daniel  Kukolj George
Affiliation:Department of Biotechnology, College of Engineering and Bioproducts Research Center, Yonsei University, 134 Shinchon-Dong, Seodaemun-Gu, Seoul, 120-749, South Korea
Abstract:Using fluorescein isothiocyanate (FITC)-conjugated H-2K(b) CTL epitope (SIINFEKL) as a model system, we investigated the antigen delivery route by pH-sensitive liposomes in vivo. Fluorescence was initially detected in lymph nodes at 3 h after immunization, and its intensity reached a peak value in superticial inguinal lymph node at 9 h. No trace could be detected in spleen even with prolonged monitoring for up to 24 h. These results strongly suggest that the presentation of CTL-peptide antigen vehicled by pH-sensitive liposomes exclusively occurs in lymph nodes. In mice immunized with the H-2K(b) CTL epitope encapsulated pH-sensitive liposomes, peptide-specific CTL response was detected at day 3. The response was strongly augmented by the second immunization and persisted up to at least 45 days. These results suggest that pH-sensitive liposome formula functions as a potential adjuvant of peptide antigens and is useful for the induction of antigen specific CTLsv in vivo.
Keywords:Hepatitis C virus   HCV   RNA-dependent RNA polymerase   NS5B   De novo RNA synthesis   3-Untranslated region
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