Production of hepatitis B defective particles is dependent on liver status

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• 作者：Francois Redelsperger^a ; ^b ; ^c ; ¹ ; Bouchra Lekbaby^a ; ^b ; ^c ; ¹ ; Yassmina Mandouri^a ; ^b ; ^c ; Eric Giang^a ; ^b ; ^c ; Marion Duriez^a ; ^b ; ^c ; Nathalie Desire^d ; ^e ; Anne-marie Roque Afonso^f ; Segolene Brichler^g ; Pascal Dubreuil^h ; Anca Dobrinⁱ ; Gabriel Perlemuterⁱ ; Sophie Prevot^j ; Nathalie Bacon^d ; Jean Didier Grange^k ; Fadila Zatla^d ; Catherine Le Pendeven^d ; Stanislas Pol^c ; ^l ; Helene Strick-Marchand^m ; James Di Santo^m ; Dina Kremsdorf^a ; ^b ; ^c ; Patrick Soussan^a ; ^b ; ^c ; ^d ; ^e ; ^{patrick.soussan@inserm.fr}
• 关键词：Hepatitis B virus ; Defective particle ; Splice ; Liver disease
• 刊名：Virology
• 出版年：2012
• 期刊代码：108_00426822
• 类别：imm
• 出版时间：15-30 September, 2012
• 卷：431
• 期：1-2
• 页码：21-28
• 文件大小：580 K

摘要

Defective hepatitis B virus (dHBV) generated from spliced RNA is detected in the sera of HBV-chronic carriers. Our study was designed to determine whether the proportion of dHBV changed during the course of infection, and to investigate whether dHBV might interfere with HBV replication. To achieve this, HBV wild-type and dHBV levels were determined by Q-PCR in sera from 56 untreated chronic patients and 23 acute patients, in sequential samples from 4 treated-patients and from liver-humanized mice after HBV infection.

The proportion of dHBV was higher in patients with severe compared to null/moderate liver disease or with acute infection. Follow-up showed that the proportion of dHBV increased during disease progression. By contrast, a low and stable proportion of dHBV was observed in the humanized-mouse model of HBV infection.

Our results highlight a regulation of the proportion of dHBV during liver disease progression that is independent of interference with viral replication.