Hepatitis C virus lacking the hypervariable region 1 of the second envelope protein is infectious and causes acute resolving or persistent infection in chimpanzees

Persistent infection with hepatitis C virus (HCV) is among the leading caus es of chronic liver disease. Previous studies suggested that genetic variat ion in hypervariable region 1 (HVR1) of the second envelope protein, possib ly in response to host immune pressure, influences the outcome of HCV infec tion. In the present study, a chimpanzee transfected intrahepatically with RNA transcripts of an infectious HCV clone (pCV-H77C) from which HVR1 was d eleted became infected; the Delta HVR1 virus was subsequently transmitted t o a second chimpanzee, Infection with Delta HVR1 virus resulted in persiste nt infection in the former chimpanzee and in acute resolving infection in t he latter chimpanzee. Both chimpanzees developed hepatitis. The Delta HVR1 virus initially replicated to low titers, but virus titer increased signifi cantly after mutations appeared in the viral genome, Thus, wild-type HCV wi thout HVR1 was apparently attenuated, suggesting a functional role of HVR1, However, our data indicate that HVR1 is not essential for the viability of HCV, the resolution of infection, or the progression to chronicity.