A DEFECTIVE INTERFERENCE-LIKE PHENOMENON OF HUMAN HEPATITIS-B VIRUS IN CHRONIC CARRIERS

Defective interfering (DI) particles have been found in many RNA and D NA viruses of bacteria, plants, and animals since their first discover y in influenza virus. However, this fundamental phenomenon has not bee n demonstrated in human natural infections. Using a new approach, here we provide the first experimental evidence for the existence of DI-li ke viruses in human chronic carriers of hepatitis B virus (HBV). Funct ional characterization of naturally occurring core internal deletion ( CID) variants of HBV revealed all of the features of DI particles. Whe n equal amounts of wild-type and CID variant DNAs were cotransfected i nto a human hepatoma cell line, Huh7, a three- to fivefold enrichment of CID variants was most often observed. The fluctuations of the virus populations between CID variants and helper HBV in three chronic carr iers are reminiscent of the cycling phenomenon in other DI viral syste ms. This finding has important implications for chronic viral hepatiti s and other chronic progressive viral diseases.