Evidence map›Paper›PMID 18523584›Full record

ArticlePloS one2008

Quantitative effect of suboptimal codon usage on translational efficiency of mRNA encoding HIV-1 gag in intact T cells.

Kholiswa C Ngumbela, Kieran P Ryan, Rohini Sivamurthy, Mark A Brockman, Rajesh T Gandhi, Nina Bhardwaj, Daniel G Kavanagh

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

32 citing papers in PubMed, 66 citations in OpenAlex.

  1. Transgene sequence codon optimization and composition determines replication competence of self-amplifying RNA.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Emerging translation strategies during virus-host interaction.Wiley interdisciplinary reviews. RNA · 2021
    Review
  11. Article
  12. HIV Rev-isited.Open biology · 2020
    Review
  13. Article
  14. mRNA as novel technology for passive immunotherapy.Cellular and molecular life sciences : CMLS · 2019
    Review
  15. The adaptation of codon usage of +ssRNA viruses to their hosts.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2018
    Article
  16. Article
  17. Codon Optimization Leads to Functional Impairment of RD114-TR Envelope Glycoprotein.Molecular therapy. Methods & clinical development · 2017
    Article
  18. Article
  19. Article
  20. Article
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

7 authors at 4 institutions in 2 countries.

Kholiswa C NgumbelaHIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu Natal, Durban, South Africa.
Kieran P Ryan
Rohini Sivamurthy
Mark A Brockman
Rajesh T Gandhi
Nina Bhardwaj
Daniel G Kavanagh
Harvard University · USMassachusetts General Hospital · USNew York University · USUniversity of KwaZulu-Natal · ZA

Funding

Induction of Immunity by Non-Replicating HIV-1R37AI044628 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BHARDWAJ, NINA · 2004 to 2014
$4.2M
Induction of HIV-specific Immune ResponsesR01AI066992 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI GANDHI, RAJESH T · 2006 to 2010
$2.7M
The T cell response to rapidly evolving HIV antigensF32AI058457 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI KAVANAGH, DANIEL GARRETT · 2004 to 2006
$149k
NIAID NIH HHS F32 AI058457NIAID NIH HHS F32AI058457NIAID NIH HHS R01AI0571278-03NIAID NIH HHS R01 AI066992NIAID NIH HHS R01AI066992NIAID NIH HHS R37 AI044628NIAID NIH HHS R37AI044628-08
6 · The paper itself

Abstract

backgroundThe sequences of wild-isolate strains of Human Immunodeficiency Virus-1 (HIV-1) are characterized by low GC content and suboptimal codon usage. Codon optimization of DNA vectors can enhance protein expression both by enhancing translational efficiency, and by altering RNA stability and export. Although gag codon optimization is widely used in DNA vectors and experimental vaccines, the actual effect of altered codon usage on gag translational efficiency has not been quantified. METHODOLOGY AND PRINCIPAL

findingsTo quantify translational efficiency of gag mRNA in live T cells, we transfected Jurkat cells with increasing doses of capped, polyadenylated synthetic mRNA corresponding to wildtype or codon-optimized gag sequences, measured Gag production by quantitative ELISA and flow cytometry, and estimated the translational efficiency of each transcript as pg of Gag antigen produced per microg of input mRNA. We found that codon optimization yielded a small increase in gag translational efficiency (approximately 1.6 fold). In contrast when cells were transfected with DNA vectors requiring nuclear transcription and processing of gag mRNA, codon optimization resulted in a very large enhancement of Gag production.

conclusionsWe conclude that suboptimal codon usage by HIV-1 results in only a slight loss of gag translational efficiency per se, with the vast majority of enhancement in protein expression from DNA vectors due to altered processing and export of nuclear RNA.

Indexed as

CodonProtein BiosynthesisEnzyme-Linked Immunosorbent AssayGene Products, gagHIV-1HumansJurkat CellsRNA, MessengerT-LymphocytesCodonGene Products, gagRNA, Messenger

Identifiers

PMID18523584
PMCPMC2387063
OpenAlexW2087375630

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.