AUTHOR=Sadahiro Akitoshi , Fukao Akira , Kosaka Mio , Funakami Yoshinori , Takizawa Naoki , Takeuchi Osamu , Duncan Kent E. , Fujiwara Toshinobu TITLE=Translation of Hepatitis A Virus IRES Is Upregulated by a Hepatic Cell-Specific Factor JOURNAL=Frontiers in Genetics VOLUME=9 YEAR=2018 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2018.00307 DOI=10.3389/fgene.2018.00307 ISSN=1664-8021 ABSTRACT=

Many viruses strongly prefer to infect certain cell types, a phenomenon known as “tropism.” Understanding tropism’s molecular basis is important for the design of vaccines and antiviral therapy. A common mechanism involves viral protein interactions with cell-specific surface receptors, but intracellular mechanisms involving translation have also been described. In this report, we focus on Hepatitis A Virus (HAV) tissue tropism from the standpoint of the translational machinery. HAV genomic RNA, like other positive stranded RNA viruses, is devoid of a cap structure and its translation is driven by highly structured RNA sequences termed internal ribosome entry site (IRES) in the 5′ untranslated region (UTR). Unlike most viral IRESs, HAV IRES-mediated translation requires eIF4E and the 3′ end of HAV RNA is polyadenylated. However, the molecular mechanism of HAV IRES-mediated translation initiation remains poorly understood. We analyzed HAV-IRES-mediated translation in a cell-free system derived from either non-hepatic cells (HeLa) or hepatoma cells (Huh-7) that enables investigation of the contribution of the cap and the poly(A) tail. This revealed that HAV IRES-mediated translation activity in hepatoma cell extracts is higher as compared to extracts derived from a non-hepatic line. Our data suggest that HAV IRES-mediated translation is upregulated by a hepatic cell-specific activator in a poly(A) tail-independent manner.