Evidence map›Paper›PMID 29891700›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2018

HIV-1 gag recruits PACSIN2 to promote virus spreading.

Sergei Popov, Elena Popova, Michio Inoue, Yuanfei Wu, Heinrich Göttlinger

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.6field-weighted citation impact, top 19% 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

15 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
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  4. Article
  5. PACSIN proteins in vivo: Roles in development and physiology.Acta physiologica (Oxford, England) · 2022
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. HIV-1 packs in PACSIN2 for cell-to-cell spread.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Sergei PopovDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605.
Elena PopovaDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605.
Michio InoueDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605.
Yuanfei WuDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605.
Heinrich GöttlingerDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605 heinrich.gottlinger@umassmed.edu.
University of Massachusetts Chan Medical School · US

Funding

Mechanism of HIV Cell-Cell Transmission of Relevance to Substance UsersDP1DA038034 · NIDA · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI GOTTLINGER, HEINRICH · 2014 to 2018
$4.2M
MOLECULAR BIOLOGY OF HIV GAG PROTEINSR01AI029873 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI GOTTLINGER, HEINRICH · 1990 to 2018
$3.7M
NIAID NIH HHS R01 AI029873NIDA NIH HHS DP1 DA038034
6 · The paper itself

Abstract

The p2b domain of Rous sarcoma virus (RSV) Gag and the p6 domain of HIV-1 Gag contain late assembly (L) domains that engage the ESCRT membrane fission machinery and are essential for virus release. We now show that the PPXY-type RSV L domain specifically recruits the BAR domain protein PACSIN2 into virus-like particles (VLP), in addition to the NEDD4-like ubiquitin ligase ITCH and ESCRT pathway components such as TSG101. PACSIN2, which has been implicated in the remodeling of cellular membranes and the actin cytoskeleton, is also recruited by HIV-1 p6 independent of its ability to engage the ESCRT factors TSG101 or ALIX. Moreover, PACSIN2 is robustly recruited by NEDD4-2s, a NEDD4-like ubiquitin ligase capable of rescuing HIV-1 budding defects. The NEDD4-2s-induced incorporation of PACSIN2 into VLP correlated with the formation of Gag-ubiquitin conjugates, indicating that PACSIN2 binds ubiquitin. Although PACSIN2 was not required for a single cycle of HIV-1 replication after infection with cell-free virus, HIV-1 spreading was nevertheless severely impaired in T cell lines and primary human peripheral blood mononuclear cells depleted of PACSIN2. HIV-1 spreading could be restored by reintroduction of wild-type PACSIN2, but not of a SH3 domain mutant unable to interact with the actin polymerization regulators WASP and N-WASP. Overall, our observations indicate that PACSIN2 promotes the cell-to-cell spreading of HIV-1 by connecting Gag to the actin cytoskeleton.

Indexed as

Actin CytoskeletonAdaptor Proteins, Signal TransducingCell Line, TumorEndosomal Sorting Complexes Required for Transportgag Gene Products, Human Immunodeficiency VirusHIV-1HIV InfectionsHumansMutationProtein DomainsRepressor Proteinssrc Homology DomainsUbiquitin-Protein LigasesVirus ReplicationAdaptor Proteins, Signal TransducingEndosomal Sorting Complexes Required for Transportgag Gene Products, Human Immunodeficiency VirusITCH protein, humanPACSIN2 protein, humanRepressor ProteinsUbiquitin-Protein LigasesGagHIV-1PACSIN2ubiquitinvirus spreading

Identifiers

PMID29891700
PMCPMC6142272
OpenAlexW2808094455

What OpenQuestion holds

Textmetadata
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.