ArticleProceedings of the National Academy of Sciences of the United States of America2022
The ZCCHC14/TENT4 complex is required for hepatitis A virus RNA synthesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- The Post-Transcriptional Regulatory Element of Hepatitis B Virus: From Discovery to Therapy.Viruses · 2024Pooled it
- Sex differences in hepatitis A virus infection in mice.PLoS pathogens · 2026Article
- Primer- and template-independent RNA polymerization by terminal nucleotidyltransferase TENT4B.Nucleic acids research · 2026Article
- Advances and perspectives in animal models of human hepatitis A virus.Animal models and experimental medicine · 2026Review
- Host species-specific mutations in the thumb domain of the 3Dpol polymerase are required for efficient replication of human hepatitis A virus in mice.PLoS pathogens · 2026Article
- Navigating the Viral Hepatitis Drug Landscape: New Discoveries and Enduring Challenges. A Narrative Review.Infectious diseases and therapy · 2026Review
- Review
- RNA stability enhancers for durable base-modified mRNA therapeutics.Nature biotechnology · 2025Article
- TENT5C functions as a corepressor in the ligand-bound glucocorticoid receptor and estrogen receptor α complexes.The FEBS journal · 2025Article
- Heat shock protein 90 chaperone activity is required for hepatitis A virus replication.Journal of virology · 2025Article
- Noncanonical Poly(A) Polymerase TENT4 Drives Expression of Subgenomic Hepatitis A Virus RNAs in Infected Cells.Viruses · 2025Article
- Hepato-selective dihydroquinolizinones active against hepatitis A virus in vitro and in vivo.Antiviral research · 2025Article
- Hepatovirus translation requires PDGFA-associated protein 1, an eIF4E-binding protein regulating endoplasmic reticulum stress responses.Science advances · 2024Article
- Dual Roles of Host Zinc Finger Proteins in Viral RNA Regulation: Decay or Stabilization.International journal of molecular sciences · 2024Review
- 8-Oxoguanine DNA Glycosylase1 conceals oxidized guanine in nucleoprotein-associated RNA of respiratory syncytial virus.PLoS pathogens · 2024Article
- Epidemiologic and clinical updates on viral infections in Saudi Arabia.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Article
- Biochemical analysis of the host factor activity of ZCCHC14 in hepatitis A virus replication.Journal of virology · 2024Article
- "PROTAC" modified dihydroquinolizinones (DHQs) that cause degradation of PAPD-5 and inhibition of hepatitis A virus and hepatitis B virus, in vitro.Bioorganic & medicinal chemistry letters · 2024Article
- Loxapine inhibits replication of hepatitis A virus in vitro and in vivo by targeting viral protein 2C.PLoS pathogens · 2024Article
- Hepatoviruses promote very-long-chain fatty acid and sphingolipid synthesis for viral RNA replication and quasi-enveloped virus release.Science advances · 2023Article
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
Despite excellent vaccines, resurgent outbreaks of hepatitis A have caused thousands of hospitalizations and hundreds of deaths within the United States in recent years. There is no effective antiviral therapy for hepatitis A, and many aspects of the hepatitis A virus (HAV) replication cycle remain to be elucidated. Replication requires the zinc finger protein ZCCHC14 and noncanonical TENT4 poly(A) polymerases with which it associates, but the underlying mechanism is unknown. Here, we show that ZCCHC14 and TENT4A/B are required for viral RNA synthesis following translation of the viral genome in infected cells. Cross-linking immunoprecipitation sequencing (CLIP-seq) experiments revealed that ZCCHC14 binds a small stem-loop in the HAV 5' untranslated RNA possessing a Smaug recognition-like pentaloop to which it recruits TENT4. TENT4 polymerases lengthen and stabilize the 3' poly(A) tails of some cellular and viral mRNAs, but the chemical inhibition of TENT4A/B with the dihydroquinolizinone RG7834 had no impact on the length of the HAV 3' poly(A) tail, stability of HAV RNA, or cap-independent translation of the viral genome. By contrast, RG7834 inhibited the incorporation of 5-ethynyl uridine into nascent HAV RNA, indicating that TENT4A/B function in viral RNA synthesis. Consistent with potent in vitro antiviral activity against HAV (IC
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