Suppression of mRNA accumulation by the duck hepatitis B virus reverse transcriptase.
Hepadnaviruses establish chronic liver infections, but the mechanisms of persistence and immune evasion are poorly understood. We previously found that the duck hepatitis B virus (DHBV) and hepatitis B virus reverse transcriptases (P protein) unexpectedly accumulate in the cytoplasm where they could affect function(s) beyond viral DNA synthesis, such as gene expression. Therefore, we measured effects of DHBV P on gene expression from reporter constructs and the viral genome. P reduced reporter expression at the mRNA level to approximately 30-40%, independent of reporter tested. Accumulation of the viral pregenomic RNA from its native promoter was suppressed three-to four-fold by P, and accumulation of the capsid protein and intracellular core particles was similarly suppressed because the pregenomic RNA encodes the capsid protein. Therefore, suppression of the pregenomic RNA by DHBV P creates a negative feedback loop to limit viral antigen accumulation and replication, possibly contributing to maintenance of chronic infection.
Cao
Feng
F
Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1402 S. Grand Blvd., St. Louis, MO 63104, USA. caof@slu.edu
Tavis
John E
JE
D000818:Animals; D045744:Cell Line, Tumor; D002645:Chickens; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter; D015611:Hepatitis B Virus, Duck / Q000201:enzymology / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism*; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics
D004279:DNA, Viral; D012333:RNA, Messenger; D012367:RNA, Viral; D012194:RNA-Directed DNA Polymerase; D001616:beta-Galactosidase