ArticleProceedings of the National Academy of Sciences of the United States of America2023
Human FAM111A inhibits vaccinia virus replication by degrading viral protein I3 and is antagonized by poxvirus host range factor SPI-1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- MMF inhibits poxvirus infection by disrupting IMPDH2 interaction with USP5 and inducing its rod-and-ring assemblies.Virologica Sinica · 2026Article
- Poxvirus A52 protein subverts autophagy flux by blocking autophagosome-lysosome fusion to promote viral replication.PLoS pathogens · 2026Article
- The FAM111A Gene: Genetic, Epigenetic, and Pharmacological Targets and Mechanistic Insights with Clinical Relevance.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Blocking Lysine Crotonylation and Aerobic Glycolysis as Targeting Strategy Against mpox Virus Replication.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Poxvirus H5 mediates the formation of liquid-liquid phase separation condensates which promote virus factory assembly.PLoS pathogens · 2025Article
- Lumpy Skin Disease Virus Pathogenesis: Viral Protein Functions and Comparative Insights from Vaccinia Virus.Animals : an open access journal from MDPI · 2025Review
- Poxvirus Host-Range Determinants: SAMD9/9L and Beyond.Annual review of virology · 2025Review
- Review
- Exploring the function and pathogenicity of Goatpox virus N1L gene using recombinant vaccinia virus Tiantan strain.Frontiers in veterinary science · 2025Article
- Kenny-Caffey Syndrome Type 2 (KCS2): A New Case Report and Patient Follow-Up Optimization.Journal of clinical medicine · 2024Article
- E2F3-dependent activation of FAM111B restricts mouse cytomegalovirus replication in primate cells.Journal of virology · 2024Article
- The multifaceted roles of selective autophagy receptors in viral infections.Journal of virology · 2024Review
- Abortive Infection of Animal Cells: What Goes Wrong.Annual review of virology · 2024Review
- Trimerized S expressed by modified vaccinia virus Ankara (MVA) confers superior protection against lethal SARS-CoV-2 challenge in mice.Journal of virology · 2024Article
- Unravelling the Intricate Roles of FAM111A and FAM111B: From Protease-Mediated Cellular Processes to Disease Implications.International journal of molecular sciences · 2024Review
- Complement C3 deposition restricts the proliferation of internalizedFrontiers in cellular and infection microbiology · 2024Article
- Quantitative proteomics defines mechanisms of antiviral defence and cell death during modified vaccinia Ankara infection.Nature communications · 2023Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Zoonotic poxviruses such as mpox virus (MPXV) continue to threaten public health safety since the eradication of smallpox. Vaccinia virus (VACV), the prototypic poxvirus used as the vaccine strain for smallpox eradication, is the best-characterized member of the poxvirus family. VACV encodes a serine protease inhibitor 1 (SPI-1) conserved in all orthopoxviruses, which has been recognized as a host range factor for modified VACV Ankara (MVA), an approved smallpox vaccine and a promising vaccine vector. FAM111A (family with sequence similarity 111 member A), a nuclear protein that regulates host DNA replication, was shown to restrict the replication of a VACV SPI-1 deletion mutant (VACV-ΔSPI-1) in human cells. Nevertheless, the detailed antiviral mechanisms of FAM111A were unresolved. Here, we show that FAM111A is a potent restriction factor for VACV-ΔSPI-1 and MVA. Deletion of FAM111A rescued the replication of MVA and VACV-ΔSPI-1 and overexpression of FAM111A significantly reduced viral DNA replication and virus titers but did not affect viral early gene expression. The antiviral effect of FAM111A necessitated its trypsin-like protease domain and DNA-binding domain but not the PCNA-interacting motif. We further identified that FAM111A translocated into the cytoplasm upon VACV infection by degrading the nuclear pore complex via its protease activity, interacted with VACV DNA-binding protein I3, and promoted I3 degradation through autophagy. Moreover, SPI-1 from VACV, MPXV, or lumpy skin disease virus was able to antagonize FAM111A by prohibiting its nuclear export. Our findings reveal the detailed mechanism by which FAM111A inhibits VACV and provide explanations for the immune evasive function of VACV SPI-1.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.