Synonymous Codon Pair Recoding of the HIV-1 env Gene Affects Virus Replication Capacity
Jordan de Paiz, Ana (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Franco Cirera, Sandra (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Martinez, Miguel Angel (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)

Date:	2021
Abstract:	Synonymous codon pair deoptimization is an efficient strategy for virus attenuation; however, the underlying mechanism remains controversial. Here, we optimized and deoptimized the codon pair bias (CPB) of the human immunodeficiency virus type 1 (HIV-1) envelope (env) gene to investigate the influence of env synonymous CPB recoding on virus replication capacity, as well as the potential mechanism. We found that env CPB deoptimization did not always generate attenuation, whereas CPB optimization attenuated virus replication in MT-4 cells. Furthermore, virus attenuation correlated with reduced Env protein production but not with decreased viral RNA synthesis. Remarkably, in our model, increasing the number of CpG dinucleotides in the 5' end of env did not reduce the replication capacity of HIV-1. These results indicate that factors other than CPB or CpG content may have impacted the viral fitness of the synonymously recoded study variants. Our findings provide evidence that CPB recoding-associated attenuation can affect translation efficiency. Moreover, we demonstrated that an increased number of CpGs in the 5' end of HIV-1 env is not always associated with reduced virus replication capacity.
Grants:	Agencia Estatal de Investigación PID2019-103955RB-100 Ministerio de Economía y Competitividad BES-2014-069931
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Codon pair bias ; Synonymous gene recoding ; HIV-1 ; Envelope ; Fitness ; Attenuation
Published in:	Cells, Vol. 10 (june 2021) , ISSN 2073-4409

DOI: 10.3390/cells10071636
PMID: 34209946

10 p, 949.6 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 > Research articles
Articles > Published articles