Proteins specifically binding to the 3' untranslated region of hepatitis A virus RNA in persistently infected cells

Abstract

Establishment of persistency is the common result of hepatitis A virus (HAV) infection in most HAV/cell culture systems. Previous studies provided evidence that shortly before or concomitantly with establishment of persistent infections synthesis of viral RNA is down-regulated. This may be an effect of regulating factors. Using RNA/protein binding assays it was shown that, at the critical time during virus replication, proteins accumulate which interact specifically with a distinct nucleotide sequence (HPE) within the 3' non-coding region of the HAV genome and/or (HME) within the 5' terminal region of the HAV antigenome. The sequences consist of 23 nucleotides (HPE: 5'-AAAUUUUCUUAAAAUUUCUGAGG-3'; HME: 5'-CCUCAGAAAUUUUAAGAAAAUUU-3'). A sequence with 79% similarity was found in the corresponding 3' non-coding region of poliovirus type I (Sabin) RNA. The latter sequence was shown to bind proteins from HAV infected cells but comparable proteins were absent in cells infected poliovirus.