Evidence map›Paper›PMID 32553106›Full record

ArticleeLife2020

MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface.

Richard J Miles, Claire Kerridge, Laura Hilditch, Christopher Monit, David A Jacques, Greg J Towers

Open access · goldAbstract read
In one paragraph

Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Cyclophilin A Regulates Tripartite Motif 5 Alpha Restriction of HIV-1.International journal of molecular sciences · 2025
    Review
  3. Article
  4. Article
  5. Capsid-host interactions for HIV-1 ingress.Microbiology and molecular biology reviews : MMBR · 2023
    Review
  6. Review
  7. Article
  8. Review
  9. The capsid lattice engages a bipartite NUP153 motif to mediate nuclear entry of HIV-1 cores.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  10. HIV-1 mutants expressing B cell clonogenic matrix protein p17 variants are increasing their prevalence worldwide.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Richard J MilesDivision of Infection and Immunity, University College London, London, United Kingdom.
Claire KerridgeDivision of Infection and Immunity, University College London, London, United Kingdom.
Laura HilditchDivision of Infection and Immunity, University College London, London, United Kingdom.
Christopher MonitDivision of Infection and Immunity, University College London, London, United Kingdom.
David A JacquesEMBL Australia Node in Single Molecule Science and ARC Centre of Excellence in Advanced Molecular Imaging, School of Medical Sciences, University of New South Wales, Sydney, Australia.ORCID 0000-0002-6426-4510
Greg J TowersDivision of Infection and Immunity, University College London, London, United Kingdom.ORCID 0000-0002-7707-0264
University College London · GBUNSW Sydney · AU

Funding

Medical Research Council G0801172Medical Research Council MR/S023380/1Wellcome Trust
6 · The paper itself

Abstract

The type one interferon induced restriction factor Myxovirus resistance B (MxB) restricts HIV-1 nuclear entry evidenced by inhibition of 2-LTR but not linear forms of viral DNA. The HIV-1 capsid is the key determinant of MxB sensitivity and cofactor binding defective HIV-1 capsid mutants P90A (defective for cyclophilin A and Nup358 recruitment) and N74D (defective for CPSF6 recruitment) have reduced dependency on nuclear transport associated cofactors, altered integration targeting preferences and are not restricted by MxB expression. This has suggested that nuclear import mechanism may determine MxB sensitivity. Here we have use genetics to separate HIV-1 nuclear import cofactor dependence from MxB sensitivity. We provide evidence that MxB sensitivity depends on HIV-1 capsid conformation, rather than cofactor recruitment. We show that depleting CPSF6 to change nuclear import pathway does not impact MxB sensitivity, but mutants that recapitulate the effect of Cyclophilin A binding on capsid conformation and dynamics strongly impact MxB sensitivity. We demonstrate that HIV-1 primary isolates have different MxB sensitivities due to cytotoxic T lymphocyte (CTL) selected differences in Gag sequence but similar cofactor dependencies. Overall our work demonstrates a complex relationship between cyclophilin dependence and MxB sensitivity likely driven by CTL escape. We propose that cyclophilin binding provides conformational flexibility to HIV-1 capsid facilitating simultaneous evasion of capsid-targeting restriction factors including TRIM5 as well as MxB.

Indexed as

Active Transport, Cell NucleusCapsidHIV-1HumansMyxovirus Resistance ProteinsMX2 protein, humanMyxovirus Resistance Proteinscapsidcyclophilin AHIVhumaninfectious diseasemicrobiologyMxBrestriction factorvirus

Identifiers

PMID32553106
PMCPMC7299335
OpenAlexW3036637977

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.