Evidence map›Paper›PMID 25524560›Full record

ArticleRetrovirology2014

Kinetic variations between reverse transcriptases of viral protein X coding and noncoding lentiviruses.

Gina M Lenzi, Robert A Domaoal, Dong-Hyun Kim, Raymond F Schinazi, Baek Kim

Open access · goldAbstract readComparative Study
In one paragraph

Article in Retrovirology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

17 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. 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

5 authors at 4 institutions in 2 countries.

Gina M LenziCenter for Drug Discovery, Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, 1760 Haygood Drive, Atlanta, GA, USA. glenzi@emory.edu.
Robert A DomaoalCenter for Drug Discovery, Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, 1760 Haygood Drive, Atlanta, GA, USA. robert.domaoal@emory.edu.
Dong-Hyun KimCollege of Pharmacy, Kyung-Hee University, Seoul, South Korea. dhkim@khu.ac.kr.
Raymond F SchinaziCenter for Drug Discovery, Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, 1760 Haygood Drive, Atlanta, GA, USA. rschina@emory.edu.
Baek KimCenter for Drug Discovery, Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, 1760 Haygood Drive, Atlanta, GA, USA. baek.kim@emory.edu.
Emory University · USJohns Hopkins University Center for AIDS ResearchKyung Hee University · KRVeterans Health Administration · US

Funding

Virology and Molecular Biomarkers CoreP30AI050409 · NIAID · EMORY UNIVERSITY · PI Carlos del Rio · 2002 to 2026
$74.0M
Graduate Training in the Pharmacological StudiesT32GM008602 · NIGMS · EMORY UNIVERSITY · PI HALL, RANDY A. · 1996 to 2021
$5.1M
Replication fidelity and lentiviral pathogenesisR01AI049781 · NIAID · UNIVERSITY OF ROCHESTER · PI KIM, BAEK · 2002 to 2016
$4.9M
SAMHD1 controls dNTP pool and HIV sensitivity to NRTIsR01GM104198 · NIGMS · UNIVERSITY OF ROCHESTER · PI KIM, BAEK · 2012 to 2018
$2.3M
NIAID NIH HHS 5P30-AI-50409NIAID NIH HHS AI049781NIAID NIH HHS P30 AI050409NIAID NIH HHS R01 AI049781NIGMS NIH HHS GM104198NIGMS NIH HHS R01 GM104198NIGMS NIH HHS T32 GM008602
6 · The paper itself

Abstract

backgroundHost SAM domain and HD domain-containing protein 1 (SAMHD1) suppresses reverse transcription kinetics of HIV-1 in nondividing cells such as macrophages by hydrolyzing and nearly depleting cellular dNTPs, which are the substrates of viral reverse transcriptase (RT). However, unlike HIV-1, HIV-2 and SIVsm encode viral protein X (Vpx), which counteracts the dNTPase activity of SAMHD1 and elevates dNTP concentration, allowing the viruses to replicate under abundant dNTP conditions even in nondividing cells.

findingsHere we tested whether RTs of these Vpx coding and noncoding lentiviruses display different enzyme kinetic profiles in response to dNTP concentrations. For this test, we characterized an extensive collection of RTs from 7 HIV-1 strains, 4 HIV-2 strains and 7 SIV strains, and determined their steady-state kinetic parameters. The K m values of all HIV-1 RTs were consistently low and close to the low dNTP concentrations found in macrophages. However, the K m values of SIV and HIV-2 RTs were not only higher than those of HIV-1 RTs but also varied significantly, indicating that HIV-2/SIV RTs require higher dNTP concentrations for efficient DNA synthesis, compared to HIV-1 RT. However, the k cat values of all eighteen lentiviral RTs were very similar.

conclusionsOur biochemical analysis supports the hypothesis that the enzymological properties, particularly, K m values, of lentivirus RTs, are mechanistically tied with the cellular dNTP availability in nondividing target cells, which is controlled by SAMHD1 and Vpx.

Indexed as

HIV-1HIV-2KineticsNucleotidesRNA-Directed DNA PolymeraseSimian Immunodeficiency VirusNucleotidesRNA-Directed DNA Polymerase

Identifiers

PMID25524560
PMCPMC4282736
OpenAlexW2137406317

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.