Evidence map›Paper›PMID 26669976›Full record

ArticleScientific reports2015

A small molecule compound IMB-LA inhibits HIV-1 infection by preventing viral Vpu from antagonizing the host restriction factor BST-2.

Zeyun Mi, Jiwei Ding, Quan Zhang, Jianyuan Zhao, Ling Ma, Haisheng Yu, Zhenlong Liu, Guangzhi Shan, Xiaoyu Li, Jinming Zhou and 5 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

13 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Limiting Respiratory Viral Infection by Targeting Antiviral and Immunological Functions of BST-2/Tetherin: Knowledge and Gaps.BioEssays : news and reviews in molecular, cellular and developmental biology · 2018
    Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. NK Cells in HIV Disease.Current HIV/AIDS reports · 2016
    Review
  13. 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

15 authors at 7 institutions in 2 countries.

Zeyun MiInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing 100050, China.
Jiwei DingInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing 100050, China.
Quan ZhangInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing 100050, China.
Jianyuan ZhaoBeijing Union University, Beijing 100101, China.
Ling MaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing 100050, China.
Haisheng YuInstitute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Zhenlong LiuLady Davis Institute-Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
Guangzhi ShanInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing 100050, China.
Xiaoyu LiInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing 100050, China.
Jinming ZhouInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing 100050, China.
Tao WeiBeijing Union University, Beijing 100101, China.
Liguo ZhangInstitute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Fei GuoInstitute of Pathogen Biology, Chinese Academy of Medical Science, Beijing, China.
Chen LiangLady Davis Institute-Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
Shan CenInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing 100050, China.
Chinese Academy of Medical Sciences & Peking Union Medical College · CNBeijing Union University · CNChinese Academy of Sciences · CNInstitute of Biophysics · CNJewish General Hospital · CAMcGill University · CATianjin Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human BST-2 inhibits HIV-1 replication by tethering nascent virions to the cell surface. HIV-1 codes Vpu that counteracts BST-2 by down-regulating this restriction factor from the cell surface. This important function makes Vpu a potential therapeutic target. Yet, no agents have been reported to block Vpu from antagonizing BST-2. In this study, we report a small molecule compound IMB-LA that abrogates the function of Vpu and thereby strongly suppresses HIV-1 replication by sensitizing the virus to BST-2 restriction. Further studies revealed that IMB-LA specifically inhibits Vpu-mediated degradation of BST-2 and restores the expression of BST-2 at the cell surface. Although IMB-LA does not prevent Vpu from interacting with BST-2 or β-TrCP2-containing ubiquitin E3 ligase, sorting of BST-2 into lysosomes in Vpu-expressing cells is blocked by IMB-LA. Most importantly, HIV-1 release and infection is inhibited by IMB-LA only in BST-2-expressing cells. In summary, results herein demonstrated that IMB-LA could specifically inhibit the degradation of BST-2 induced by Vpu, and impair HIV-1 replication in a BST-2 dependent manner, suggesting the feasibility of utilizing small molecule compounds to disable the antagonist function of Vpu and thereby expose HIV-1 to the restriction by BST-2.

Indexed as

Antigens, CDAnti-Retroviral AgentsHIV InfectionsHuman Immunodeficiency Virus ProteinsViral Regulatory and Accessory ProteinsBone Marrow Stromal Antigen 2GPI-Linked ProteinsHEK293 CellsHeLa CellsHIV-1HumansProteolysisViroporin ProteinsVirus ReplicationAntigens, CDAnti-Retroviral AgentsBone Marrow Stromal Antigen 2BST2 protein, humanGPI-Linked ProteinsHuman Immunodeficiency Virus ProteinsViral Regulatory and Accessory ProteinsViroporin Proteinsvpu protein, Human immunodeficiency virus 1

Identifiers

PMID26669976
PMCPMC4680884
OpenAlexW2204621792

What OpenQuestion holds

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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.