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Codon usage optimization of HIV type 1 subtype C gag, pol, env, and nef genes: in vitro expression and immune responses in DNA-vaccinated mice.

Publication ,  Journal Article
Gao, F; Li, Y; Decker, JM; Peyerl, FW; Bibollet-Ruche, F; Rodenburg, CM; Chen, Y; Shaw, DR; Allen, S; Musonda, R; Shaw, GM; Zajac, AJ ...
Published in: AIDS Res Hum Retroviruses
September 2003

Codon usage optimization of human immunodeficiency virus type 1 (HIV-1) structural genes has been shown to increase protein expression in vitro as well as in the context of DNA vaccines in vivo; however, all optimized genes reported thus far are derived from HIV-1 (group M) subtype B viruses. Here, we report the generation and biological characterization of codon usage-optimized gag, pol, env (gp160, gp140, gp120), and nef genes from a primary (nonrecombinant) HIV-1 subtype C isolate. After transfection into 293T cells, optimized subtype C genes expressed one to two orders of magnitude more protein (as determined by immunoblot densitometry) than the corresponding wild-type constructs. This effect was most pronounced for gp160, gp140, Gag, and Pol (>250-fold), but was also observed for gp120 and Nef (45- and 20-fold, respectively). Optimized gp160- and gp140-derived glycoproteins were processed, incorporated into virus particles, and mediated virus entry when expressed in trans to complement an env-minus HIV-1 provirus. Mice immunized with optimized gp140 DNA developed antibody as well as CD4+ and CD8+ T cell immune responses that were orders of magnitude greater than those of mice immunized with wild-type gp140 DNA. These data confirm and extend previous studies of codon usage optimization of HIV-1 genes to the most prevalent group M subtype. Our panel of matched optimized and wild-type subtype C genes should prove valuable for studies of protein expression and function, the generation of subtype-specific immunological reagents, and the production of DNA-based sub-unit vaccines directed against a broader spectrum of viruses.

Duke Scholars

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Published In

AIDS Res Hum Retroviruses

DOI

ISSN

0889-2229

Publication Date

September 2003

Volume

19

Issue

9

Start / End Page

817 / 823

Location

United States

Related Subject Headings

  • Virology
  • Vaccines, DNA
  • Mice, Inbred BALB C
  • Mice
  • Interferon-gamma
  • HIV-1
  • Genes, pol
  • Genes, nef
  • Genes, gag
  • Genes, env
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gao, F., Li, Y., Decker, J. M., Peyerl, F. W., Bibollet-Ruche, F., Rodenburg, C. M., … Hahn, B. H. (2003). Codon usage optimization of HIV type 1 subtype C gag, pol, env, and nef genes: in vitro expression and immune responses in DNA-vaccinated mice. AIDS Res Hum Retroviruses, 19(9), 817–823. https://doi.org/10.1089/088922203769232610
Gao, Feng, Yingying Li, Julie M. Decker, Fred W. Peyerl, Frederic Bibollet-Ruche, Cynthia M. Rodenburg, Yalu Chen, et al. “Codon usage optimization of HIV type 1 subtype C gag, pol, env, and nef genes: in vitro expression and immune responses in DNA-vaccinated mice.AIDS Res Hum Retroviruses 19, no. 9 (September 2003): 817–23. https://doi.org/10.1089/088922203769232610.
Gao F, Li Y, Decker JM, Peyerl FW, Bibollet-Ruche F, Rodenburg CM, et al. Codon usage optimization of HIV type 1 subtype C gag, pol, env, and nef genes: in vitro expression and immune responses in DNA-vaccinated mice. AIDS Res Hum Retroviruses. 2003 Sep;19(9):817–23.
Gao, Feng, et al. “Codon usage optimization of HIV type 1 subtype C gag, pol, env, and nef genes: in vitro expression and immune responses in DNA-vaccinated mice.AIDS Res Hum Retroviruses, vol. 19, no. 9, Sept. 2003, pp. 817–23. Pubmed, doi:10.1089/088922203769232610.
Gao F, Li Y, Decker JM, Peyerl FW, Bibollet-Ruche F, Rodenburg CM, Chen Y, Shaw DR, Allen S, Musonda R, Shaw GM, Zajac AJ, Letvin N, Hahn BH. Codon usage optimization of HIV type 1 subtype C gag, pol, env, and nef genes: in vitro expression and immune responses in DNA-vaccinated mice. AIDS Res Hum Retroviruses. 2003 Sep;19(9):817–823.
Journal cover image

Published In

AIDS Res Hum Retroviruses

DOI

ISSN

0889-2229

Publication Date

September 2003

Volume

19

Issue

9

Start / End Page

817 / 823

Location

United States

Related Subject Headings

  • Virology
  • Vaccines, DNA
  • Mice, Inbred BALB C
  • Mice
  • Interferon-gamma
  • HIV-1
  • Genes, pol
  • Genes, nef
  • Genes, gag
  • Genes, env