HCMV UL97 phosphotransferase gene mutations may be associated with antiviral resistance in immunocompromised patients in Belém, PA, Northern Brazil
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFPA |
Texto Completo: | http://repositorio.ufpa.br/jspui/handle/2011/10015 http://dx.doi.org/10.1590/0037-8682-0345-2017 |
Resumo: | Human cytomegalovirus is one of the causes of opportunist infections in immunocompromised patients, and is triggered by factors such as state of viral latency, weakened immune responses, and development of antiviral resistance to ganciclovir, the only drug offered by the public health system in Brazil to treat the infection. The goal of this study was to identify mutations that may be associated with antiviral resistance in immunocompromised patients. Methods: Molecular analysis was performed in 82 blood samples and subjected to genomic DNA extraction by a silica-based method. Three sequences of the HCMV UL97 gene, which encodes a phosphotransferase protein required for activation of ganciclovir, were amplified by polymerase chain reaction. Pyrosequencing methods were applied to one external 2096-bp segment DNA and two internal sequences between nucleotides 1087 to 1828 to detect mutations in this gene. Results: Approximately 10% of sequences contained mutations between nucleotides 377 and 594, in conserved regions of the UL97 gene, leading to amino acid changes. Eleven coding mutations were identified, including changes leading to amino acid substitutions, E596K and S604F, which were observed in 100% of samples and are described for the first time in Brazil. In addition, one mutation (A594V) that is associated with ganciclovir resistance was detected in a kidney transplant patient. Conclusions: Further studies to detect mutations associated with HCMV resistance to antiviral drugs are required to demonstrate the need to increase the variety and availability of drugs used to treat viral infections in the public health care system in Brazil. |
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2018-06-13T19:47:40Z2018-06-13T19:47:40Z2018-04SILVA, Dorotéa de Fátima Lobato da et al. HCMV UL97 phosphotransferase gene mutations may be associated with antiviral resistance in immunocompromised patients in Belém, PA, Northern Brazil. Revista da Sociedade Brasileira de Medicina Tropical, Uberaba, v. 51, n. 2, p. 141-145, mar./abr. 2018. Disponível em: <http://repositorio.ufpa.br/jspui/handle/2011/10015>. Acesso em:.0037-86821678-9849http://repositorio.ufpa.br/jspui/handle/2011/10015http://dx.doi.org/10.1590/0037-8682-0345-2017Human cytomegalovirus is one of the causes of opportunist infections in immunocompromised patients, and is triggered by factors such as state of viral latency, weakened immune responses, and development of antiviral resistance to ganciclovir, the only drug offered by the public health system in Brazil to treat the infection. The goal of this study was to identify mutations that may be associated with antiviral resistance in immunocompromised patients. Methods: Molecular analysis was performed in 82 blood samples and subjected to genomic DNA extraction by a silica-based method. Three sequences of the HCMV UL97 gene, which encodes a phosphotransferase protein required for activation of ganciclovir, were amplified by polymerase chain reaction. Pyrosequencing methods were applied to one external 2096-bp segment DNA and two internal sequences between nucleotides 1087 to 1828 to detect mutations in this gene. Results: Approximately 10% of sequences contained mutations between nucleotides 377 and 594, in conserved regions of the UL97 gene, leading to amino acid changes. Eleven coding mutations were identified, including changes leading to amino acid substitutions, E596K and S604F, which were observed in 100% of samples and are described for the first time in Brazil. In addition, one mutation (A594V) that is associated with ganciclovir resistance was detected in a kidney transplant patient. Conclusions: Further studies to detect mutations associated with HCMV resistance to antiviral drugs are required to demonstrate the need to increase the variety and availability of drugs used to treat viral infections in the public health care system in Brazil.engUniversidade Federal do ParáUFPABrasilRevista da Sociedade Brasileira de Medicina Tropicalhttp://www.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822018000200141&lng=pt&nrm=isoreponame:Repositório Institucional da UFPAinstname:Universidade Federal do Pará (UFPA)instacron:UFPACNPQ::CIENCIAS DA SAUDE::SAUDE COLETIVA::SAUDE PUBLICACitomegalovírusMutagêneseResistência antiviralMutaçõesFosfotransferaseHCMV UL97 phosphotransferase gene mutations may be associated with antiviral resistance in immunocompromised patients in Belém, PA, Northern Brazilinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article5102141145http://lattes.cnpq.br/5064843368253793http://lattes.cnpq.br/6338193279074109http://lattes.cnpq.br/0476330416864057http://lattes.cnpq.br/5600822689860398http://lattes.cnpq.br/0734229589851760http://lattes.cnpq.br/9163804242420760http://lattes.cnpq.br/3560941703812539SILVA, Dorotéa de Fátima Lobato daCARDOSO, Jedson FerreiraSILVA, Sandro Patroca daARRUDA, Leda Mani França deMEDEIROS, Renato Lopes Fernandes deMORAES, Marluce Matos deSOUSA, Rita Catarina Medeirosinfo:eu-repo/semantics/openAccessORIGINALArtigo_HcmvUl97Phosphotransferase.pdfArtigo_HcmvUl97Phosphotransferase.pdfapplication/pdf980334http://repositorio.ufpa.br/oai/bitstream/2011/10015/1/Artigo_HcmvUl97Phosphotransferase.pdfa15ca8675797152a5732051ea9146922MD51CC-LICENSElicense_urllicense_urltext/plain; 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dc.title.pt_BR.fl_str_mv |
HCMV UL97 phosphotransferase gene mutations may be associated with antiviral resistance in immunocompromised patients in Belém, PA, Northern Brazil |
title |
HCMV UL97 phosphotransferase gene mutations may be associated with antiviral resistance in immunocompromised patients in Belém, PA, Northern Brazil |
spellingShingle |
HCMV UL97 phosphotransferase gene mutations may be associated with antiviral resistance in immunocompromised patients in Belém, PA, Northern Brazil SILVA, Dorotéa de Fátima Lobato da CNPQ::CIENCIAS DA SAUDE::SAUDE COLETIVA::SAUDE PUBLICA Citomegalovírus Mutagênese Resistência antiviral Mutações Fosfotransferase |
title_short |
HCMV UL97 phosphotransferase gene mutations may be associated with antiviral resistance in immunocompromised patients in Belém, PA, Northern Brazil |
title_full |
HCMV UL97 phosphotransferase gene mutations may be associated with antiviral resistance in immunocompromised patients in Belém, PA, Northern Brazil |
title_fullStr |
HCMV UL97 phosphotransferase gene mutations may be associated with antiviral resistance in immunocompromised patients in Belém, PA, Northern Brazil |
title_full_unstemmed |
HCMV UL97 phosphotransferase gene mutations may be associated with antiviral resistance in immunocompromised patients in Belém, PA, Northern Brazil |
title_sort |
HCMV UL97 phosphotransferase gene mutations may be associated with antiviral resistance in immunocompromised patients in Belém, PA, Northern Brazil |
author |
SILVA, Dorotéa de Fátima Lobato da |
author_facet |
SILVA, Dorotéa de Fátima Lobato da CARDOSO, Jedson Ferreira SILVA, Sandro Patroca da ARRUDA, Leda Mani França de MEDEIROS, Renato Lopes Fernandes de MORAES, Marluce Matos de SOUSA, Rita Catarina Medeiros |
author_role |
author |
author2 |
CARDOSO, Jedson Ferreira SILVA, Sandro Patroca da ARRUDA, Leda Mani França de MEDEIROS, Renato Lopes Fernandes de MORAES, Marluce Matos de SOUSA, Rita Catarina Medeiros |
author2_role |
author author author author author author |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/5064843368253793 http://lattes.cnpq.br/6338193279074109 http://lattes.cnpq.br/0476330416864057 http://lattes.cnpq.br/5600822689860398 http://lattes.cnpq.br/0734229589851760 http://lattes.cnpq.br/9163804242420760 http://lattes.cnpq.br/3560941703812539 |
dc.contributor.author.fl_str_mv |
SILVA, Dorotéa de Fátima Lobato da CARDOSO, Jedson Ferreira SILVA, Sandro Patroca da ARRUDA, Leda Mani França de MEDEIROS, Renato Lopes Fernandes de MORAES, Marluce Matos de SOUSA, Rita Catarina Medeiros |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::SAUDE COLETIVA::SAUDE PUBLICA |
topic |
CNPQ::CIENCIAS DA SAUDE::SAUDE COLETIVA::SAUDE PUBLICA Citomegalovírus Mutagênese Resistência antiviral Mutações Fosfotransferase |
dc.subject.por.fl_str_mv |
Citomegalovírus Mutagênese Resistência antiviral Mutações Fosfotransferase |
description |
Human cytomegalovirus is one of the causes of opportunist infections in immunocompromised patients, and is triggered by factors such as state of viral latency, weakened immune responses, and development of antiviral resistance to ganciclovir, the only drug offered by the public health system in Brazil to treat the infection. The goal of this study was to identify mutations that may be associated with antiviral resistance in immunocompromised patients. Methods: Molecular analysis was performed in 82 blood samples and subjected to genomic DNA extraction by a silica-based method. Three sequences of the HCMV UL97 gene, which encodes a phosphotransferase protein required for activation of ganciclovir, were amplified by polymerase chain reaction. Pyrosequencing methods were applied to one external 2096-bp segment DNA and two internal sequences between nucleotides 1087 to 1828 to detect mutations in this gene. Results: Approximately 10% of sequences contained mutations between nucleotides 377 and 594, in conserved regions of the UL97 gene, leading to amino acid changes. Eleven coding mutations were identified, including changes leading to amino acid substitutions, E596K and S604F, which were observed in 100% of samples and are described for the first time in Brazil. In addition, one mutation (A594V) that is associated with ganciclovir resistance was detected in a kidney transplant patient. Conclusions: Further studies to detect mutations associated with HCMV resistance to antiviral drugs are required to demonstrate the need to increase the variety and availability of drugs used to treat viral infections in the public health care system in Brazil. |
publishDate |
2018 |
dc.date.accessioned.fl_str_mv |
2018-06-13T19:47:40Z |
dc.date.available.fl_str_mv |
2018-06-13T19:47:40Z |
dc.date.issued.fl_str_mv |
2018-04 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
SILVA, Dorotéa de Fátima Lobato da et al. HCMV UL97 phosphotransferase gene mutations may be associated with antiviral resistance in immunocompromised patients in Belém, PA, Northern Brazil. Revista da Sociedade Brasileira de Medicina Tropical, Uberaba, v. 51, n. 2, p. 141-145, mar./abr. 2018. Disponível em: <http://repositorio.ufpa.br/jspui/handle/2011/10015>. Acesso em:. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufpa.br/jspui/handle/2011/10015 |
dc.identifier.issn.pt_BR.fl_str_mv |
0037-8682 1678-9849 |
dc.identifier.doi.pt_BR.fl_str_mv |
http://dx.doi.org/10.1590/0037-8682-0345-2017 |
identifier_str_mv |
SILVA, Dorotéa de Fátima Lobato da et al. HCMV UL97 phosphotransferase gene mutations may be associated with antiviral resistance in immunocompromised patients in Belém, PA, Northern Brazil. Revista da Sociedade Brasileira de Medicina Tropical, Uberaba, v. 51, n. 2, p. 141-145, mar./abr. 2018. Disponível em: <http://repositorio.ufpa.br/jspui/handle/2011/10015>. Acesso em:. 0037-8682 1678-9849 |
url |
http://repositorio.ufpa.br/jspui/handle/2011/10015 http://dx.doi.org/10.1590/0037-8682-0345-2017 |
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eng |
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