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A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses
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Synonymous Codon Pair Recoding of the HIV-1 env Gene Affects Virus Replication Capacity
Ana Jordan-Paiz1, Sandra Franco1, Miguel Angel Martinez1
1IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), 08916 Badalona, Spain.
Cells
|July 2, 2021
Summary
Synonymous codon pair optimization, not deoptimization, attenuated human immunodeficiency virus type 1 (HIV-1) replication by reducing Env protein production. CpG content did not significantly impact viral fitness in this study.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Synonymous codon pair deoptimization is a strategy for virus attenuation, but its mechanism is debated.
- The codon pair bias (CPB) influences gene expression and viral fitness.
Purpose of the Study:
- To investigate the impact of synonymous codon pair bias (CPB) recoding in the HIV-1 envelope (env) gene on viral replication.
- To explore the underlying mechanisms of CPB-mediated attenuation and the role of CpG content.
Main Methods:
- Optimization and deoptimization of CPB in the HIV-1 env gene.
- Assessment of viral replication capacity in MT-4 cells.
- Measurement of viral RNA synthesis and Env protein production.
- Analysis of CpG dinucleotide content in the 5' end of the env gene.
Main Results:
- CPB optimization, not deoptimization, attenuated HIV-1 replication in MT-4 cells.
- Attenuation correlated with reduced Env protein levels, not viral RNA synthesis.
- Increased CpG dinucleotides in the 5' env region did not consistently reduce viral replication capacity.
Conclusions:
- Synonymous CPB recoding can impact viral fitness, primarily by affecting translation efficiency and protein production.
- The influence of CPB on viral attenuation is context-dependent and may not solely rely on CpG content.
- Further research is needed to elucidate the complex interplay of genetic factors influencing viral fitness.
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