TY - JOUR
T1 - Biologic properties of hepatitis B viral genomes with mutations in the precore promoter and precore open reading frame
AU - Scaglioni, Pier Paolo
AU - Melegari, Margherita
AU - Wands, Jack R.
N1 - Funding Information:
This work was supported by Grants CA-35711 and AA-02169 from the National Institutes of Health and the Tan Yan Kee Foundation. M.M. was supported in part by a fellowship from the ‘‘A. Castelnuovo’’ Foundation, Varese, Italy. The authors gratefully thank Dorothy A. Fallows for the gift of the pCMVHBV plasmid and Rolf Carlson for artwork.
PY - 1997/7/7
Y1 - 1997/7/7
N2 - It is now well recognized that mutations in the hepatitis B virus (HBV) genome occur during the natural course of chronic vital infection. Regions of the viral genome that are frequently affected by such mutations, rearrangements, and/or deletions generally involve the precore promoter, precore, and core as well as the preS gene regions. However, little is known regarding the biologic consequences of these mutations on the functional properties of the variant viral strains with respect to effects on viral replication. In this study, we investigated the functional significance of precore promoter and precore gene mutations that reduce or abolish the synthesis of hepatitis B e antigen (HBeAg). We found that precore promoter mutations diminished the expression of HBeAg but did not affect the synthesis of pregenomic RNA. However, these precore mutations were associated with a modest increase in HBW replication. In contrast, a naturally occurring mutant that carries a termination codon in position 28 of the precore open reading frame demonstrated increased encapsidation of pregenomic mRNA into nucleocapsid particles. Consequently, this variant vital strain demonstrated e substantial increase in the level of viral replication compared to 'wild- type' HBV and other precore promoter mutant viral strains. These studies suggest that substitutions in the precore promoter and precore gene not only alter the synthesis of HBeAg but also affect the level of vital replication.
AB - It is now well recognized that mutations in the hepatitis B virus (HBV) genome occur during the natural course of chronic vital infection. Regions of the viral genome that are frequently affected by such mutations, rearrangements, and/or deletions generally involve the precore promoter, precore, and core as well as the preS gene regions. However, little is known regarding the biologic consequences of these mutations on the functional properties of the variant viral strains with respect to effects on viral replication. In this study, we investigated the functional significance of precore promoter and precore gene mutations that reduce or abolish the synthesis of hepatitis B e antigen (HBeAg). We found that precore promoter mutations diminished the expression of HBeAg but did not affect the synthesis of pregenomic RNA. However, these precore mutations were associated with a modest increase in HBW replication. In contrast, a naturally occurring mutant that carries a termination codon in position 28 of the precore open reading frame demonstrated increased encapsidation of pregenomic mRNA into nucleocapsid particles. Consequently, this variant vital strain demonstrated e substantial increase in the level of viral replication compared to 'wild- type' HBV and other precore promoter mutant viral strains. These studies suggest that substitutions in the precore promoter and precore gene not only alter the synthesis of HBeAg but also affect the level of vital replication.
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U2 - 10.1006/viro.1997.8594
DO - 10.1006/viro.1997.8594
M3 - Article
C2 - 9217060
AN - SCOPUS:0030750617
SN - 0042-6822
VL - 233
SP - 374
EP - 381
JO - Virology
JF - Virology
IS - 2
ER -