ArticleProceedings of the National Academy of Sciences of the United States of America2023
HIV-1 usurps transcription start site heterogeneity of host RNA polymerase II to maximize replication fitness.
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 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 21 citations in OpenAlex.
- Mechanisms of HIV-1 assembly, release and maturation.Nature reviews. Microbiology · 2026Review
- CryoGO enables high-resolution structural profiling of endogenous cellular macromolecules.bioRxiv : the preprint server for biology · 2026Article
- Transcription start site heterogeneity controls MDA5 sensing of unspliced HIV-1 RNAs.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Influenza hemagglutinin subtypes have different sequence constraints despite sharing extremely similar structures.bioRxiv : the preprint server for biology · 2026Article
- Enhanced transcriptional insulation of lentiviral vectors using "sequence-upgraded polyA long terminal repeats" or "supA-LTRs".Molecular therapy. Advances · 2026Article
- Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication.FEMS microbiology reviews · 2026Review
- Host restriction factors and p17-Driven inflammaging in HIV-1: From molecular pathogenesis to functional cure.AIMS microbiology · 2026Review
- Influenza hemagglutinin subtypes have different sequence constraints despite sharing extremely similar structures.Virus evolution · 2026Article
- GABARAP proteins regulate the packaging of HIV-1 genomic RNA into virions.EMBO reports · 2025Article
- 5' cap sequestration is required for sensing of unspliced HIV-1 RNA by MDA5.bioRxiv : the preprint server for biology · 2025Article
- How to recover from a bad start: adaptation of HIV-1 transcription start site mutants during serial passaging in culture.Journal of virology · 2025Article
- Review
- HIV-1 single-transcription start-site mutants display complementary replication functions that are restored by reversion.Journal of virology · 2025Article
- The Complex Interactions Between HIV-1 and Human Host Cell Genome: From Molecular Mechanisms to Clinical Practice.International journal of molecular sciences · 2025Review
- Article
- Review
- HIV capsids: orchestrators of innate immune evasion, pathogenesis and pandemicity.The Journal of general virology · 2025Review
- HIV-1 single transcription start site mutants display complementary replication functions that are restored by reversion.bioRxiv : the preprint server for biology · 2024Article
- Translation of HIV-1 unspliced RNA is regulated by 5' untranslated region structure.Journal of virology · 2024Article
- Distinct negative-sense RNA viruses induce a common set of transcripts encoding proteins forming an extensive network.Journal of virology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
HIV-1 relies on host RNA polymeraseII (Pol II) to transcribe its genome and uses multiple transcription start sites (TSS), including three consecutive guanosines located near the U3-R junction, to generate transcripts containing three, two, and one guanosine at the 5' end, referred to as 3G, 2G, and 1G RNA, respectively. The 1G RNA is preferentially selected for packaging, indicating that these 99.9% identical RNAs exhibit functional differences and highlighting the importance of TSS selection. Here, we demonstrate that TSS selection is regulated by sequences between the CATA/TATA box and the beginning of R. Furthermore, we have generated two HIV-1 mutants with distinct 2-nucleotide modifications that predominantly express 3G RNA or 1G RNA. Both mutants can generate infectious viruses and undergo multiple rounds of replication in T cells. However, both mutants exhibit replication defects compared to the wild-type virus. The 3G-RNA-expressing mutant displays an RNA genome-packaging defect and delayed replication kinetics, whereas the 1G-RNA-expressing mutant exhibits reduced Gag expression and a replication fitness defect. Additionally, reversion of the latter mutant is frequently observed, consistent with sequence correction by plus-strand DNA transfer during reverse transcription. These findings demonstrate that HIV-1 maximizes its replication fitness by usurping the TSS heterogeneity of host RNA Pol II to generate unspliced RNAs with different specialized roles in viral replication. The three consecutive guanosines at the junction of U3 and R may also maintain HIV-1 genome integrity during reverse transcription. These studies reveal the intricate regulation of HIV-1 RNA and complex replication strategy.
Indexed as
Identifiers
What OpenQuestion holds
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.