Related Experiment Video
Updated: May 9, 2026

Pairwise Growth Competition Assay for Determining the Replication Fitness of Human Immunodeficiency Viruses
Published on: May 4, 2015
Changes in codon-pair bias of human immunodeficiency virus type 1 have profound effects on virus replication in cell
Gloria Martrus1, Maria Nevot, Cristina Andres
1Fundació irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), Badalona 08916, Spain.
Background:
Human immunodeficiency virus type 1 (HIV-1) has a biased nucleotide composition different from human genes. This raises the question of how evolution has chosen the nucleotide sequence of HIV-1 that is observed today, or to what extent the actual encoding contributes to virus replication capacity, evolvability and pathogenesis. Here, we applied the previously described synthetic attenuated virus engineering (SAVE) approach to HIV-1.
Results:
Using synonymous codon pairs, we rationally recoded and codon pair-optimized and deoptimized different moieties of the HIV-1 gag and pol genes. Deoptimized viruses had significantly lower viral replication capacity in MT-4 and peripheral blood mononuclear cells (PBMCs). Varying degrees of ex vivo attenuation were obtained, depending upon both the specific deoptimized region and the number of deoptimized codons. A protease optimized virus carrying 38 synonymous mutations was not attenuated and displayed a replication capacity similar to that of the wild-type virus in MT-4 cells and PBMCs. Although attenuation is based on several tens of nucleotide changes, deoptimized HIV-1 reverted to wild-type virulence after serial passages in MT-4 cells. Remarkably, no reversion was observed in the optimized virus.
Conclusion:
These data demonstrate that SAVE is a useful strategy to phenotypically affect the replicative properties of HIV-1.
More Related Videos
14:23A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses
Published on: August 31, 2014
13:13Single-cell Quantitation of mRNA and Surface Protein Expression in Simian Immunodeficiency Virus-infected CD4+ T Cells Isolated from Rhesus macaques
Published on: September 25, 2018
Related Concept Videos
Viral Mutations
Retrovirus Life Cycles
Leaky Scanning
Size and Structure of Viral Genomes
Inhibitors of Viral Protein Synthesis