Changes in codon-pair bias of human immunodeficiency virus type 1 have profound effects on virus replication in cell culture
Martrus, Gloria (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Nevot Banús, Maria (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Andrés, Cristina (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Clotet Sala, Bonaventura (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Martinez, Miguel Ángel (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)

Date:	2013
Abstract:	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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; Versió publicada
Subject:	Codon-pair bias ; HIV ; Attenuation ; Evolution
Published in:	Retrovirology, Vol. 10, N. 78 (25 July 2013) , p. 1-12, ISSN 1742-4690

DOI: 10.1186/1742-4690-10-78
PMID: 23885919

12 p, 786.4 KB	Additional file 1 1 p, 4.6 KB	Additional file 2 2 p, 94.3 KB	Additional file 3 1 p, 6.0 KB	Additional file 4 4 p, 22.8 KB	Additional file 5 4 p, 18.9 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Published articles