In many other positive-strand RNA viruses, including the related flaviviruses, conserved sequences or structures at or near the 3′ end represent cis elements critical for viral replication (reviewed in ref. However, the importance of different conserved elements of the 3′ UTR of HCV has not been established experimentally.The development of infectious c DNA clones of HCV (14–16) and the refinement of transfection techniques (16) have made it feasible to test the effect of various mutations on the ability of HCV to replicate in the only validated animal model, the chimpanzee.I’ve been in the business for more than 20 years and I have a lot of experience and a point of view and a vision,” says Lathan.…
Mutants lacking all or part of the 3′ terminal conserved region or the poly(U–UC) region were unable to infect the chimpanzee, indicating that both regions are critical for infectivity .
However, the third region, the variable region, was able to tolerate a deletion that destroyed the two putative stem–loop structures within this region.
Mutant VR-24 containing a deletion of the proximal 24 nt of the variable region of the 3′ UTR was viable in the chimpanzee and seemed to replicate as well as the undeleted parent virus.
The chimpanzee became viremic 1 week after inoculation with mutant VR-24, and the HCV genome titer increased over time during the early acute infection.
Therefore, the poly(U–UC) region and the conserved region, but not the variable region, of the 3′ UTR seem to be critical for More than 170 million people worldwide are infected chronically with the hepatitis C virus (HCV; ref.