ArticleJournal of virology2020
CpG Dinucleotides Inhibit HIV-1 Replication through Zinc Finger Antiviral Protein (ZAP)-Dependent and -Independent Mechanisms.
Article in Journal of virology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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Who cites it
58 citing papers in PubMed, 84 citations in OpenAlex.
- A feline coronavirus nucleocapsid protein disrupts ZC3HAV1-viral RNA association to counteract host RNA-level restriction.PLoS pathogens · 2026Article
- Divergent host adaptation in Marburg virus: a hypothesis-generating framework for prioritizing non-traditional reservoirs.BMC genomics · 2026Article
- Increased or decreased numbers of CpG dinucleotide motifs in the genome of influenza A virus do not affectJournal of virology · 2026Article
- Temporal Dynamics of Innate Immune Activation and Viral Interference During Sequential Co-Infection with Influenza A Virus and SARS-CoV-2: Molecular Mechanisms, Clinical Evidence, and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Deciphering 6-mer Spectra Distribution Rules in Coronavirus Genomes: Application to Comparative Genomic Analysis.International journal of molecular sciences · 2026Article
- RNA editing signatures and codon adaptation reveal potential translational compatibility between Hendra virus and its natural host Pteropus Alecto.Archives of microbiology · 2025Article
- Mapping evolutionary paradigm of bovine viral diarrhea virusVirulence · 2025Article
- KHNYN is a manganese-dependent endoribonuclease required for ZAP-mediated antiviral restriction.Nucleic acids research · 2025Article
- Effect of increased CpG and UpA dinucleotides in the West Nile virus genome on virus transmission byJournal of virology · 2025Article
- Mammalian antiviral proteins ZAP and KHNYN can independently restrict CpG-enriched avian viruses.PLoS biology · 2025Article
- Mammalian ZAP and KHNYN can independently restrict CpG-enriched avian viruses.bioRxiv : the preprint server for biology · 2025Article
- HIV-2 evades restriction by ZAP through adaptations in the U3 LTR region despite increased CpG levels.Nucleic acids research · 2025Article
- Deciphering the Code of Viral-Host Adaptation Through Maximum-Entropy Nucleotide Bias Models.Molecular biology and evolution · 2025Article
- Dengue virus preferentially uses human and mosquito non-optimal codons.Molecular systems biology · 2024Article
- Review
- Positive selection analyses identify a single WWE domain residue that shapes ZAP into a more potent restriction factor against alphaviruses.PLoS pathogens · 2024Article
- Review
- Selection on synonymous sites: the unwanted transcript hypothesis.Nature reviews. Genetics · 2024Review
- Article
- Differential Selection for Translation Efficiency Shapes Translation Machineries in Bacterial Species.Microorganisms · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
CpG dinucleotides are suppressed in the genomes of many vertebrate RNA viruses, including HIV-1. The cellular antiviral protein ZAP (zinc finger antiviral protein) binds CpGs and inhibits HIV-1 replication when CpGs are introduced into the viral genome. However, it is not known if ZAP-mediated restriction is the only mechanism driving CpG suppression. To determine how CpG dinucleotides affect HIV-1 replication, we increased their abundance in multiple regions of the viral genome and analyzed the effect on RNA expression, protein abundance, and infectious-virus production. We found that the antiviral effect of CpGs was not correlated with their abundance. Interestingly, CpGs inserted into some regions of the genome sensitize the virus to ZAP antiviral activity more efficiently than insertions into other regions, and this sensitivity can be modulated by interferon treatment or ZAP overexpression. Furthermore, the sensitivity of the virus to endogenous ZAP was correlated with its sensitivity to the ZAP cofactor KHNYN. Finally, we show that CpGs in some contexts can also inhibit HIV-1 replication by ZAP-independent mechanisms, and one of these is the activation of a cryptic splice site at the expense of a canonical splice site. Overall, we show that the location and sequence context of the CpG in the viral genome determines its antiviral activity.
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Registered trials
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.