Navegando por Assunto "Resistência antiviral"

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Acesso aberto (Open Access)
“Citomegalovírus: diversidade genética e pesquisa de resistência antiviral em pacientes imunodeficientes da cidade de Belém”
(Universidade Federal do Pará, 2015-07-17) SILVA, Dorotéa de Fátima Lobato da; SOUSA, Rita Catarina Medeiros; http://lattes.cnpq.br/3560941703812539
Cytomegalovirus (CMV) is one of the most common cause of morbidity and mortality in immunocompromised patients because its latency and reactivation mechanism that commonly occurs in immunodeficiencies. Genetic analysis showed that the virulence of the strains may be related to genotypic diversity. The main objective of this paper was to describe the seroepidemiology profile and genetic diversity of CMV by detecting mutations that confer viral resistance to ganciclovir in immunodeficient patients from Belém city.A total of 671 samples were analyzed: 243 HIV/AIDS, 257 neoplastic patients, 112 kidney transplant and 60 people with SLE. The seroprevalence of antibodies was 96.1% and active infection and levels of 2.4% (n = 16) lower than that observed by qPCR method which corresponded to 15.63%. Differences in infection rates due to low sensitivity (5.71%) of the serological method demonstrated in screening test. The mutation research was made in 82 samples for pyrosequencing method, a 741pb segment of the UL97 gene was amplified, between 1087-1828 nucleotides. It was observed that 100% (n = 82) of samples had two mutations in amino acid in codon 596 (E596K) and another one in codon 604 (S604F). The S604F mutation was not found in other viral sequences from GenBank. Ten other mutations occurred between codons 377 and 594 in eight samples, including the A594V mutation in a renal transplant patient who ended up dying.It was concluded that the prevalence of antibodies and the epidemiological profile of the group were similar to those observed in populations of developing countries; the viral infection rates are related to viral reactivation, being underestimated by serology; sequence analysis revealed significant genetic diversity in the samples examined; detection of A594V mutation suggests circulating strains with resistance mutation.
Acesso aberto (Open Access)
HCMV UL97 phosphotransferase gene mutations may be associated with antiviral resistance in immunocompromised patients in Belém, PA, Northern Brazil
(Universidade Federal do Pará, 2018-04) 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
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.