Analysis of fitness differences of hepatitis B virus genotypes D and F using a cotransfection assay.

Abstract:

:Hepatitis B virus (HBV) circulates as a collection of genetically related variants that evolve throughout the chronic infection. Those viral variants that have the greatest fitness are fixed. We recently showed different fitness for HBV variants involved in two epidemiological situations. To understand these fitness differences better, we determined the levels of extracellular HBV DNA, the synthesis of HBV DNA intermediates, and the expression of HBeAg and HBsAg in transfection and cotransfection assays. Our results show that for the subgenotype (sgt) D1, which has an 8-nucleotide deletion (sgtD1del) and exhibits lower fitness, the levels of extracellular DNA and intracellular replicative intermediates were much lower than with sgtD1wt or sgtD1mut (G1896A), which had higher fitness. In addition, in the cotransfection assay, sgtD1del inhibited sgtD1mut but not sgtD1wt replication. We also found that sgtF1b, which exhibits higher fitness, produces significantly higher levels of both extracellular DNA and intracellular replicative intermediates than does the lower-fitness sgtF4. These results demonstrate a relationship between fitness and the replicative ability of the HBV genome in the transfection assay. In addition, the data obtained by cotransfecting cells with sgtD1del and sgtD1mut provide new information about the impact of simultaneous replication of two viral variants in the same cell system on HBV replication.

journal_name

Arch Virol

journal_title

Archives of virology

authors

Sevic I,Elizalde MM,González López Ledesma MM,Flichman DM,Campos RH

doi

10.1007/s00705-018-4090-5

subject

Has Abstract

pub_date

2019-02-01 00:00:00

pages

447-455

issue

2

eissn

0304-8608

issn

1432-8798

pii

10.1007/s00705-018-4090-5

journal_volume

164

pub_type

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