Suppression of La antigen exerts potential antiviral effects against hepatitis A virus

• Published in: PloS one 2014-07, Vol.9 (7), p.e101993
• Main Authors: Jiang, Xia, Kanda, Tatsuo, Wu, Shuang, Nakamoto, Shingo, Saito, Kengo, Shirasawa, Hiroshi, Kiyohara, Tomoko, Ishii, Koji, Wakita, Takaji, Okamoto, Hiroaki, Yokosuka, Osamu
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Antiviral agents; Autoantigens - genetics; Autoantigens - metabolism; Binding sites; Cancer; Cell culture; Cell Line, Tumor; Cellular proteins; Chemical agents; Cofactors; Dehydrogenases; Development and progression; Feasibility Studies; Gastroenterology; Gene expression; Gene Silencing; Genome, Viral - drug effects; Genome, Viral - genetics; Genomes; Health aspects; Hepatitis; Hepatitis A; Hepatitis A virus - genetics; Hepatitis A virus - physiology; Hepatovirus; Humans; Infection; Infectious diseases; Inhibition; Interferon; Janus kinase; Janus Kinases - antagonists & inhibitors; Kinases; La antigen; Liver; Liver diseases; Medicine; Medicine and health sciences; Nephrology; Protein Biosynthesis - drug effects; Protein Biosynthesis - genetics; Protein Kinase Inhibitors - pharmacology; Proteins; Replication; Ribonucleoproteins - deficiency; Ribonucleoproteins - genetics; Ribonucleoproteins - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Small Interfering - genetics; siRNA; SS-B Antigen; Therapeutic applications; Translation; Tyrphostins - pharmacology; Vaccines; Virology; Virus Replication - drug effects; Virus Replication - genetics; Viruses; Xanthenes - pharmacology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0101993

Despite the development and availability of hepatitis A virus (HAV) vaccine, HAV infection is still a major cause of acute hepatitis that occasionally leads to fatal liver disease. HAV internal ribosomal entry-site (IRES) is one of the attractive targets of antiviral agents against HAV. The aim of the present study is to evaluate the impact of La, one of the cellular proteins, on HAV IRES-mediated translation and HAV replication. We investigated the therapeutic feasibility of siRNAs specific for cellular cofactors for HAV IRES-mediated translation in cell culture. It was revealed that siRNA against La could inhibit HAV IRES activities as well as HAV subgenomic replication. We also found that the Janus kinase (JAK) inhibitors SD-1029 and AG490, which reduce La expression, could inhibit HAV IRES activities as well as HAV replication. Inhibition of La by siRNAs and chemical agents could lead to the efficient inhibition of HAV IRES-mediated translation and HAV replication in cell culture models. La might play important roles in HAV replication and is being exploited as one of the therapeutic targets of host-targeting antivirals.