FIG 1.
Infectivity of GBV-B/JFH1 chimeras in tamarins. (A) Schematics of the organization of the engineered chimeric GBV-B/JFH1 cDNAs. HCV JFH1 and GBV-B genomic sequences are represented by black and white boxes, respectively, and the ubiquitin (Ubi) gene by a gray box. Dotted lines delineate the sequences that were exchanged. Recombinants are denoted as follows: “J/” (standing for JFH1) is followed by the range of JFH1 protein sequences replaced (C-NS3pro or E-NS3pro), the virus from which corresponding sequences were derived, in superscript characters (“GB” for GBV-B), and -Ubi. (B) Tamarins W6 (dashed gray line) and W10 (black line) (left) and tamarins X2 (dashed gray line) and X5 (black line) (right) were intrahepatically inoculated (black arrows) with GBV-B-3m/SapI RNA (left) or a mixture of J/C-NS3proGB-Ubi and J/E-NS3proGB-Ubi RNAs (right), respectively. Tamarins W10 and X5 were subsequently challenged (open arrowheads) with an intravenous injection of GBV-B. Serum viral loads were quantified by RT-qPCR assays targeting either GBV-B NS5A sequence (W6, W10, and X5 after GBV-B intravenous injection) or HCV 5′ noncoding region (X2 and X5 after RNA intrahepatic inoculation). Detection limits of both assays are indicated by dotted lines. Tamarin W6 died prematurely 9 days postintrahepatic inoculation (†) due to a cause unrelated to the experiment. The follow-up of tamarin X2 was stopped at 27 weeks postinoculation as indicated by the gray double slash.