Synonymous Codon Pair Recoding of the HIV-1 env Gene Affects Virus Replication Capacity

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 influen...

Descripción completa

Detalles Bibliográficos
Autores: Jordan de Paiz, Ana|||0000-0002-3495-7201, Franco Cirera, Sandra|||0000-0003-4126-2202, Martinez, Miguel Angel|||0000-0002-6681-4950
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:256471
Acceso en línea:https://ddd.uab.cat/record/256471
https://dx.doi.org/urn:doi:10.3390/cells10071636
Access Level:acceso abierto
Palabra clave:Codon pair bias
Synonymous gene recoding
HIV-1
Envelope
Fitness
Attenuation
id ES_cf783e8f45b37be1ad5cb8a2151fc93d
oai_identifier_str oai:ddd.uab.cat:256471
network_acronym_str ES
network_name_str España
repository_id_str
spelling Synonymous Codon Pair Recoding of the HIV-1 env Gene Affects Virus Replication CapacityJordan de Paiz, Ana|||0000-0002-3495-7201Franco Cirera, Sandra|||0000-0003-4126-2202Martinez, Miguel Angel|||0000-0002-6681-4950Codon pair biasSynonymous gene recodingHIV-1EnvelopeFitnessAttenuationSynonymous 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. 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/256471https://dx.doi.org/urn:doi:10.3390/cells10071636reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2019-103955RB-100Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 BES-2014-069931open accesshttp://purl.org/coar/access_right/c_abf2Aquest 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.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2564712026-06-06T12:50:31Z
dc.title.none.fl_str_mv Synonymous Codon Pair Recoding of the HIV-1 env Gene Affects Virus Replication Capacity
title Synonymous Codon Pair Recoding of the HIV-1 env Gene Affects Virus Replication Capacity
spellingShingle Synonymous Codon Pair Recoding of the HIV-1 env Gene Affects Virus Replication Capacity
Jordan de Paiz, Ana|||0000-0002-3495-7201
Codon pair bias
Synonymous gene recoding
HIV-1
Envelope
Fitness
Attenuation
title_short Synonymous Codon Pair Recoding of the HIV-1 env Gene Affects Virus Replication Capacity
title_full Synonymous Codon Pair Recoding of the HIV-1 env Gene Affects Virus Replication Capacity
title_fullStr Synonymous Codon Pair Recoding of the HIV-1 env Gene Affects Virus Replication Capacity
title_full_unstemmed Synonymous Codon Pair Recoding of the HIV-1 env Gene Affects Virus Replication Capacity
title_sort Synonymous Codon Pair Recoding of the HIV-1 env Gene Affects Virus Replication Capacity
dc.creator.none.fl_str_mv Jordan de Paiz, Ana|||0000-0002-3495-7201
Franco Cirera, Sandra|||0000-0003-4126-2202
Martinez, Miguel Angel|||0000-0002-6681-4950
author Jordan de Paiz, Ana|||0000-0002-3495-7201
author_facet Jordan de Paiz, Ana|||0000-0002-3495-7201
Franco Cirera, Sandra|||0000-0003-4126-2202
Martinez, Miguel Angel|||0000-0002-6681-4950
author_role author
author2 Franco Cirera, Sandra|||0000-0003-4126-2202
Martinez, Miguel Angel|||0000-0002-6681-4950
author2_role author
author
dc.subject.none.fl_str_mv Codon pair bias
Synonymous gene recoding
HIV-1
Envelope
Fitness
Attenuation
topic Codon pair bias
Synonymous gene recoding
HIV-1
Envelope
Fitness
Attenuation
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/256471
https://dx.doi.org/urn:doi:10.3390/cells10071636
url https://ddd.uab.cat/record/256471
https://dx.doi.org/urn:doi:10.3390/cells10071636
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2019-103955RB-100
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 BES-2014-069931
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869420086047014912
score 15,301603

Similares en LA Referencia