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J Virol, January 1998, p. 578-584, Vol. 72, No. 1
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

A Defective Interference-Like Phenomenon of Human Hepatitis B Virus in Chronic Carriers

Thomas Ta-Tung Yuan,1 Min-Hui Lin,1 Ding-Shinn Chen,2 and Chiaho Shih1,*

Departments of Pathology, Microbiology, and Immunology, University of Texas Medical Branch, Galveston, Texas 77555-0609,1 and National Taiwan University Hospital, Taipei, Taiwan2

Received 25 April 1997/Accepted 16 September 1997

Defective interfering (DI) particles have been found in many RNA and DNA viruses of bacteria, plants, and animals since their first discovery in influenza virus. However, this fundamental phenomenon has not been demonstrated in human natural infections. Using a new approach, here we provide the first experimental evidence for the existence of DI-like viruses in human chronic carriers of hepatitis B virus (HBV). Functional characterization of naturally occurring core internal deletion (CID) variants of HBV revealed all of the features of DI particles. When equal amounts of wild-type and CID variant DNAs were cotransfected into 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 carriers are reminiscent of the cycling phenomenon in other DI viral systems. This finding has important implications for chronic viral hepatitis and other chronic progressive viral diseases.

* Corresponding author. Mailing address: Departments of Pathology, Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-0609. Phone: (409) 772-2563. Fax: (409) 747-2429. E-mail: cshih{at}utmb.edu.




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