RESUMO
Five tungsten carbide nanoparticle preparations (denoted WC1-WC5) were investigated for broad spectrum virucidal activity against four recommended model viruses. These are modified vaccinia virus Ankara (MVA), human adenovirus type 5 (HAdV-5), poliovirus type 1 (PV-1) and murine norovirus (MNV). All virucidal tests were performed two to five times using the quantitative suspension test, which is a highly standardized test method to evaluate the virucidal efficacy of disinfectants in accordance with the European norm EN 14476+A1 and the German DVV/RKI guidelines. Quantitative detection of viruses was conducted by endpoint titration and quantitative real-time PCR. Results showed that three of the five tested compounds (WC1-WC3) were able to reduce the infectivity of all model viruses by at least four log10 of tissue culture infective dose 50% per ml after 15 min, whereas the other two compounds exhibited only limited efficacy (WC4) or showed cytotoxicity (WC5). Virucidal activity of nanoparticles increased with incubation time and a dose-effect curve showed dependence of virucidal activity with particle concentration. Whereas WC1-WC4 showed little cytotoxicity, WC5 which was doped with copper exhibited a significant cytotoxic effect. These findings propose tungsten carbide nanoparticles to be very promising in terms of new disinfection techniques. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study investigates the virucidal activity of tungsten carbide nanoparticles using the quantitative suspension test in accordance with the European norm EN 14476+A1 and the German DVV/RKI guidelines. Due to highly standardized assay conditions, results of this test are considered very reliable for evaluation of the virucidal activity of disinfectants. Broad-spectrum activity and high efficacy of three different tungsten carbide nanoparticles preparations is concluded.
Assuntos
Adenovírus Humanos/efeitos dos fármacos , Desinfetantes/farmacologia , Norovirus/efeitos dos fármacos , Poliovirus/efeitos dos fármacos , Compostos de Tungstênio/farmacologia , Vaccinia virus/efeitos dos fármacos , Animais , Desinfecção/métodos , Humanos , Nanopartículas Metálicas , Camundongos , Testes de Sensibilidade MicrobianaAssuntos
Aciclovir/administração & dosagem , Antivirais/administração & dosagem , Farmacorresistência Viral , Infecções por HIV/complicações , Herpes Genital/tratamento farmacológico , Herpesvirus Humano 2/isolamento & purificação , Mutação de Sentido Incorreto , Aciclovir/farmacologia , Adulto , Antivirais/farmacologia , Técnicas de Genotipagem , Herpes Genital/virologia , Herpesvirus Humano 2/efeitos dos fármacos , Herpesvirus Humano 2/genética , Humanos , Masculino , Recidiva , Timidina Quinase/genética , Falha de Tratamento , Carga ViralRESUMO
Herpes genitalis is caused by the herpes simplex virus type 1 or type 2 and can manifest as primary or recurrent infection. It is one of the most common sexually transmitted infections and due to associated physical and psychological morbidity it constitutes a considerable, often underestimated medical problem. In addition to providing the reader with basic knowledge of the pathogen and clinical presentation of herpes genitalis, this review article discusses important aspects of the laboratory diagnostics, antiviral therapy and prophylaxis. The article is aimed at all health-care workers managing patients with herpes genitalis and attempts to improve the often suboptimal counselling, targeted use of laboratory diagnostics, treatment and preventive measures provided to patients.
RESUMO
Infections with adenovirus (AdV) and herpesviruses can result in considerable morbidity and mortality in pediatric hematopoietic stem cell transplant (SCT) recipients. Herpes simplex virus (HSV) reactivations are usually prevented by acyclovir (ACV) prophylaxis, whereas cidofovir (CDV) has been used off indication to manage AdV infections. We report a child with myelodysplastic syndrome undergoing multiple SCT, who experienced HSV-1 disease including severe mucositis and herpetic whitlow, as well as high viral load AdV DNAemia. Both ACV and CDV were ineffective; however, viral loads were decreased with brincidofovir, resulting in viral clearance. A subsequent Epstein-Barr virus disease with relevant meningoencephalitis responded to rituximab.
Assuntos
Adenoviridae/fisiologia , Infecções por Adenovirus Humanos/tratamento farmacológico , Antivirais/uso terapêutico , Citosina/análogos & derivados , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpes Simples/tratamento farmacológico , Herpes Zoster/tratamento farmacológico , Meningoencefalite/tratamento farmacológico , Mucosite/tratamento farmacológico , Síndromes Mielodisplásicas/cirurgia , Organofosfonatos/uso terapêutico , Aciclovir/administração & dosagem , Aciclovir/uso terapêutico , Adenoviridae/isolamento & purificação , Infecções por Adenovirus Humanos/sangue , Infecções por Adenovirus Humanos/virologia , Antibioticoprofilaxia , Antivirais/administração & dosagem , Pré-Escolar , Cidofovir , Citosina/administração & dosagem , Citosina/uso terapêutico , DNA Viral/sangue , Farmacorresistência Viral , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/virologia , Feminino , Foscarnet/administração & dosagem , Foscarnet/uso terapêutico , Herpes Simples/virologia , Herpes Zoster/virologia , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 3/isolamento & purificação , Herpesvirus Humano 4 , Humanos , Hospedeiro Imunocomprometido , Meningoencefalite/virologia , Mucosite/virologia , Organofosfonatos/administração & dosagem , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Carga ViralRESUMO
Varicella-zoster virus (VZV), an important member of the Herpesviridae family, is the etiological agent of varicella as primary infection and zoster as recurrence. An outstanding feature is the lifelong viral latency in dorsal root and cranial nerve ganglia. Both varicella and zoster are worldwide widespread diseases that may be associated with significant complications. However, there is a broad spectrum of laboratory methods to diagnose VZV infections. In contrast to many other viral infections, antiviral treatment of VZV infections and their prevention by vaccination or passive immunoprophylaxis are well established in medical practice. The present manuscript provides an overview about the basic knowledge of VZV infections, their laboratory diagnosis, antiviral therapy, and the prevention procedures, especially in Germany.
Assuntos
Varicela/diagnóstico , Varicela/tratamento farmacológico , Varicela/prevenção & controle , Herpesvirus Humano 3/fisiologia , Antivirais/uso terapêutico , Varicela/epidemiologia , Vacina contra Varicela/imunologia , Farmacorresistência Viral , Herpes Zoster/diagnóstico , Herpes Zoster/tratamento farmacológico , Herpes Zoster/epidemiologia , Herpes Zoster/prevenção & controle , Humanos , Imunização Passiva , Imunoensaio , Vacinação , Latência ViralRESUMO
Streptococcus (S.) pneumoniae is a major cause of secondary bacterial pneumonia during influenza epidemics. Neuraminidase (NA) is a virulence factor of both pneumococci and influenza viruses. Bacterial neuraminidases (NAs) are structurally related to viral NA and susceptible to oseltamivir, an inhibitor designed to target viral NA. This prompted us to evaluate the antipneumococcal potential of two NA inhibiting natural compounds, the diarylheptanoid katsumadain A and the isoprenylated flavone artocarpin. Chemiluminescence, fluorescence-, and hemagglutination-based enzyme assays were applied to determine the inhibitory efficiency (IC(50) value) of the tested compounds towards pneumococcal NAs. The mechanism of inhibition was studied via enzyme kinetics with recombinant NanA NA. Unlike oseltamivir, which competes with the natural substrate of NA, artocarpin exhibits a mixed-type inhibition with a Ki value of 9.70 µM. Remarkably, artocarpin was the only NA inhibitor (NAI) for which an inhibitory effect on pneumococcal growth (MIC: 0.99-5.75 µM) and biofilm formation (MBIC: 1.15-2.97 µM) was observable. In addition, we discovered that the bactericidal effect of artocarpin can reduce the viability of pneumococci by a factor of >1000, without obvious harm to lung epithelial cells. This renders artocarpin a promising natural product for further investigations.
Assuntos
Antibacterianos/farmacologia , Inibidores Enzimáticos/farmacologia , Lectinas de Ligação a Manose/farmacologia , Neuraminidase/antagonistas & inibidores , Lectinas de Plantas/farmacologia , Streptococcus pneumoniae/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Diarileptanoides/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/fisiologia , Humanos , Concentração Inibidora 50 , Cinética , Lectinas de Ligação a Manose/toxicidade , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Neuraminidase/metabolismo , Lectinas de Plantas/toxicidade , Streptococcus pneumoniae/crescimento & desenvolvimento , Streptococcus pneumoniae/fisiologiaRESUMO
After successful invasion of susceptible hosts, systemic distribution of coxsackievirus B3 (CVB3) most likely requires interactions with the endothelial system. Thereby, infection of endothelial cells occurs directly or viruses and/or virus-infected leukocytes migrate through the endothelial barrier. Many of these processes have not been studied so far. In order to analyze viral replication in the endothelium, human umbilical vein endothelial cells (HUVEC) were isolated and infected with CVB3. Time-course experiments revealed maximal viral replication at 10-24 h and viral RNA persistence up to 120 h post-infection (p. i.) without the induction of obvious general cytopathic effects or the loss of cellular viability. However, the application of the EGFP-expressing recombinant virus variant CVB3/EGFP revealed shrinkage and death of individual cells. Using infectious center assays, a noticeable CVB3 replication occurred on an average of 20 % of HUVEC at 10 h p. i. This may be in part due to a higher coxsackievirus/adenovirus receptor expression in a small subgroup of HUVEC (5-7 %) as analyzed by flow cytometry. Interestingly, CVB3 replication escalated and cellular susceptibility increased significantly after reversal of cell cycle arrest caused by serum deprivation indicating that reactivation of cellular metabolism may help to promote CVB3 replication. Finally, CVB3-infected HUVEC cultures revealed increased DNA fragmentation, and inhibition of caspase activity caused an accumulation of intracellular virus particles indicating that apoptotic processes are involved in virus release mechanisms. Based on these observations, it is assumed that CVB3 replicates efficiently in human endothelial cells. But how this specific infection of the endothelium may influence viral spread in the infected host needs to be investigated in the future.
Assuntos
Enterovirus Humano B/fisiologia , Células Endoteliais da Veia Umbilical Humana/virologia , Replicação Viral , Apoptose , Sobrevivência Celular , Células Cultivadas , Efeito Citopatogênico Viral , Humanos , Fatores de Tempo , Cultura de VírusRESUMO
The prevalence of influenza A and B virus-specific IgG was determined in sera taken between 2008 and 2010 from 1,665 children aged 0-17 years and 400 blood donors in Germany. ELISA on the basis of whole virus antigens was applied. Nearly all children aged nine years and older had antibodies against influenza A. In contrast, 40% of children aged 0-4 years did not have any influenza A virus-specific IgG antibodies. Eightysix percent of 0-6 year-olds, 47% of 7-12 year-olds and 20% of 13-17 year-olds were serologically naïve to influenza B viruses. By the age of 18 years, influenza B seroprevalence reached approximately 90%. There were obvious regional differences in the seroprevalence of influenza B in Germany. In conclusion, seroprevalences of influenza A and influenza B increase gradually during childhood. The majority of children older than eight years have basal immunity to influenza A, while comparable immunity against influenza B is only acquired at the age of 18 years. Children aged 0-6 years, showing an overall seroprevalence of 67% for influenza A and of 14% for influenza B, are especially at risk for primary infections during influenza B seasons.
Assuntos
Anticorpos Antivirais/sangue , Vírus da Influenza A/imunologia , Vírus da Influenza B/imunologia , Influenza Humana/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Alemanha/epidemiologia , Humanos , Imunoglobulina G/sangue , Lactente , Influenza Humana/sangue , Influenza Humana/imunologia , Masculino , Prevalência , Estudos Soroepidemiológicos , Adulto JovemRESUMO
Since hepatitis A virus (HAV) infection during childhood is mostly asymptomatic, only seroprevalence studies can provide reliable information on incidence of HAV infection in children. The prevalence of anti-HAV antibodies was determined in sera taken in 2008 to 2010 from 1,645 children aged 0-17 years and in sera taken in 2010-2011 from 400 adult blood donors in Germany. For examination of trend over time, 715 sera collected between 1999 and 2006 from children at the age of 0-17 years within the federal state Thuringia were included. Antibody testing was carried out using the test kits ETI-AB-HAVK PLUS and ETI-HA-IGMK PLUS from DiaSorin. In children, the overall prevalence of antibodies was 10.8 %. After the seroprevalence declined from 8.8 % among the 0-2 year-olds to 2.4 % among the 3-4 year-olds, there was a significant increase to 20.5 % in the group of the 15-17 year-olds. Boys had with 12.7 % a significantly higher seroprevalence of anti-HAV antibodies compared to 8.8 % among girls. In adult blood donors, there was a HAV seroprevalence of 19.3 %. The likelihood of past infection or immunization within the age groups of children from 0 to 12 years differed significantly from that of adults. In conclusion, in Germany, only a small number of HAV infections occur in children, especially up to the age of 12 years. The proportion of susceptible children is greater than the proportion of susceptible adults. Thus, during outbreaks, the rate of infection among children would usually be higher than the rate among adults.
Assuntos
Anticorpos Anti-Hepatite A/sangue , Hepatite A/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Feminino , Alemanha/epidemiologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Fatores Sexuais , Adulto JovemRESUMO
After allogeneic hematopoietic stem cell transplantation (HSCT), viral infections/reactivations are a frequent complication, sometimes with fatal outcome. Thus, early diagnosis is recommended by screening of whole blood or plasma preparations using highly sensitive molecular techniques that test for the most common viral pathogens, such as Epstein-Barr virus, cytomegalovirus, and adenoviruses (ADVs). Despite this approach, not every reactivation/infection can be adequately detected or excluded, even with highly sensitive polymerase chain reaction. Particularly after toxic treatment, uncommon infections or infections resistant to first-line treatment can occur, even in unusual locations. Herein, we present the case of a child with Philadelphia chromosome-positive acute lymphoblastic leukemia after allogeneic HSCT who suffered from 5 different viral reactivations/infections, including acyclovir-resistant herpes simplex virus type 1 esophagitis, human herpesvirus 6 encephalitis, rotavirus gastroenteritis, respiratory syncytial virus pneumonia, and ADV esophagitis, despite routinely performed blood examinations for viral pathogens remaining unrevealing at all times.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Viroses/diagnóstico , Viroses/virologia , Adenovírus Humanos/isolamento & purificação , Adolescente , Feminino , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 6/isolamento & purificação , Humanos , Vírus Sinciciais Respiratórios/isolamento & purificação , Rotavirus/isolamento & purificação , Transplante Homólogo/efeitos adversos , Ativação Viral , Viroses/patologiaRESUMO
Genital herpes, usually caused by herpes simplex virus type 2 (HSV-2), is one of the most common sexually transmitted diseases in humans. By contrast, intrauterine HSV-2 infections have been described rarely in the literature. Our report describes a case of neonate who was delivered after 30+2 gestational weeks by cesarean section. He presented with a respiratory distress syndrome resulting in broncho-pulmonary dysplasia. At the age of 6 weeks, a chorioretinal scar was detected. During the 4th month of age, the infant developed recurrent HSV-2 infection with nasal lesions. The retrospective type-specific serologic diagnosis revealed previous HSV-2 infection of the mother resulting in prenatal HSV-2 infection of the infant. In conclusion, intrauterine HSV-2 infections may be underrepresented since they may not be associated with severe congenital malformations and the diagnosis requires the use of HSV type-specific serologic methods not widely applied in microbiological laboratories.
Assuntos
Herpes Simples/congênito , Herpes Simples/virologia , Herpesvirus Humano 2/classificação , Herpesvirus Humano 2/isolamento & purificação , Anticorpos Antivirais/sangue , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/patologia , Displasia Broncopulmonar/virologia , Coriorretinite/patologia , Feminino , Herpes Simples/complicações , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Masculino , Nariz/patologia , Gravidez , Síndrome do Desconforto Respiratório do Recém-Nascido/complicações , Síndrome do Desconforto Respiratório do Recém-Nascido/diagnóstico , Síndrome do Desconforto Respiratório do Recém-Nascido/patologia , Síndrome do Desconforto Respiratório do Recém-Nascido/virologia , SorotipagemRESUMO
The prevalence of herpes simplex virus (HSV) type-specific IgG was determined in sera taken in 1999 to 2006 from 1,100 children aged 018 years, 800 blood donors and 200 pregnant women in Thuringia, Germany, using tests based on the HSV glycoproteins (g) gG. By the age of 1012 years, HSV-1 IgG prevalence reached 57.3%, rising to 69.3% by the age of 1618 years and to 78.0% by the age of 2830 years. Between 2.7% and 4.7% of the children aged up to 15 years had HSV-2 antibodies, increasing to 7.3% at the age of 1618 years and to 13.6% among adults. The prevalence of HSV-1 antibodies among girls was significantly lower than among boys and a significantly higher prevalence of HSV-2 IgG in women than in men was detected. The reduced incidence of HSV-1 infections during childhood, especially in girls, has to be followed up since a higher number of primary HSV-2 infections may result. Between 2.7% and 4.7% of all children tested seemed to acquire HSV-2 by intrauterine or neonatal infection. We also compared the use of gG-1 with gC-1: the agreement of 97.2% between the two ELISAs suggests that gG-1 and gC-1 can be considered equivalent antigenic targets.
Assuntos
Herpes Simples/epidemiologia , Herpesvirus Humano 1/imunologia , Herpesvirus Humano 2/imunologia , Adolescente , Adulto , Doadores de Sangue , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Alemanha/epidemiologia , Antígenos de Hepatite/imunologia , Herpes Simples/sangue , Herpes Simples/imunologia , Herpes Simples/virologia , Herpesvirus Humano 1/patogenicidade , Herpesvirus Humano 2/patogenicidade , Humanos , Imunoglobulina G/sangue , Lactente , Masculino , Gravidez , Estudos Soroepidemiológicos , Proteínas do Envelope Viral/sangue , Proteínas do Envelope Viral/imunologia , Adulto JovemRESUMO
The objective was to verify specific antibody response of varicella vaccinees to varicella-zoster virus (VZV) strains of different major clades and subclades circulating currently in Germany. The neutralization test and the fluorescent antibody to membrane antigen test measuring VZV glycoprotein (gp)-specific antibodies were used as methods. All VZV strains clustering into the main clades 1, 3 and 5 were neutralized by vaccine-induced antibodies and showed specific reaction with VZVgp-specific antibodies of vaccinees. In conclusion, this study provides first experimental evidence that varicella vaccines based on the Japanese Oka strain induce antibody response directed to VZV strains circulating currently in Germany.
Assuntos
Anticorpos Antivirais/sangue , Vacina contra Varicela/imunologia , Herpesvirus Humano 3/genética , Herpesvirus Humano 3/imunologia , Adolescente , Adulto , Anticorpos Neutralizantes/sangue , Vacina contra Varicela/administração & dosagem , Vacina contra Varicela/genética , Criança , Pré-Escolar , Genótipo , Alemanha , Humanos , Imunoensaio/métodos , Adulto JovemRESUMO
The global surveillance of varicella-zoster virus (VZV) clades is an important tool for investigation into viral evolution, host-virus interactions, role of immigration and travel for importation of viral strains as well as possible recombination events between wild- and vaccine-type VZV strains. In this prospective study, comprehensive data on the current distribution of VZV clades in Germany were collected. VZV strains from 213 patients with varicella and 109 with zoster were genotyped using the scattered single-nucleotide polymorphism method on the basis of sequencing open reading frames 1, 21, 22, 37, 50, 54 and 60. In varicella, clade 3 was detected in 45.5%, clade 1 in 30.0%, clade 5 in 21.1% and clade 2 in 0.9% of the cases. The analysis of zoster strains revealed clade 3 in 50.5%, clade 1 in 46.8%, clade 2 and clade 4 in 0.9% of the cases each. Five strains from varicella and one strain from zoster could not be attributed to any of the major and provisional VZV clades. Statistical analysis verified significantly lower frequency of clade 1 and significantly higher frequency of clade 5 in patients with varicella compared to zoster. In addition, varicella patients with clade 5 strains were significantly younger than the patients with clade 3. In conclusion, almost one half of VZV infections in Germany were caused currently by VZV clade 3. In primary VZV infection, nearly 20% of clade 1 has been replaced by clade 5 that might spread more effectively in the population than the European VZV clades.
Assuntos
Varicela/epidemiologia , Herpes Zoster/epidemiologia , Herpesvirus Humano 3/classificação , Herpesvirus Humano 3/genética , Idoso , Linhagem Celular , Varicela/virologia , Criança , Feminino , Fibroblastos/virologia , Genótipo , Alemanha/epidemiologia , Herpes Zoster/virologia , Herpesvirus Humano 3/isolamento & purificação , Humanos , Pulmão/citologia , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Fases de Leitura Aberta , Filogenia , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Prevalência , Estudos Prospectivos , Análise de Sequência de DNARESUMO
AIMS: The objective of this study was to evaluate virucidal efficacy of the commercially available povidone-iodine formulations Betaisodona solution and Betaseptic Mundipharma (Mundipharma). METHODS AND RESULTS: The quantitative suspension test for virucidal testing of biocides according to the German guideline was used as method. The use of Betaisodona solution resulted in virucidal efficacy, corresponding to >or=10(4)-fold reduction in viral titre, against vaccinia virus, bovine viral diarrhoea virus and polyomavirus SV40 within 0.5 min and adenovirus type 5 within 3-5 min without and with organic load. For inactivation of the most resistant poliovirus type 1, a time interval of >or=60 min was needed. By contrast, Betaseptic Mundipharma inactivated significantly all model viruses for virucidal testing including poliovirus type 1 within 5 min independently from the addition of proteins. CONCLUSIONS: Betaisodona solution shows a good efficacy against enveloped model viruses as well as against some nonenveloped human viruses, e.g. adenovirus and polyomavirus. Betaseptic Mundipharma has an excellent virucidal efficacy including the inactivation of the most resistent poliovirus type 1. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings of this study make Betaseptic Mundipharma suitable for virucidal disinfection of the skin within short time intervals.
Assuntos
Desinfetantes/farmacologia , Povidona-Iodo/farmacologia , Vírus/efeitos dos fármacos , Animais , Linhagem Celular , Humanos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Fatores de Tempo , Carga ViralRESUMO
Sixteen herpes simplex virus type 1 (HSV-1) and four type 2 (HSV-2) isolates resistant to acyclovir (ACV) were characterized retrospectively for drug resistance. Phenotypic testing was performed by means of tetrazolium reduction assay and genotypic analysis was carried out by sequencing of thymidine kinase (TK) and DNA-polymerase (pol) genes. All strains were characterized as cross-resistant to penciclovir, brivudin and susceptible to cidofovir. In addition, three strains were resistant to foscarnet. Genotypic analysis revealed two to seven non-synonymous mutations in the TK gene of HSV-1 and one to seven non-synonymous mutations in the DNA pol gene of HSV-1 and 2 associated with the gene polymorphism. Seventeen strains contained at least one non-synonymous resistant-related mutation in the TK gene and three strains, which were additionally foscarnet-resistant, revealed one resistance-associated mutation in the DNA pol gene. In most strains, resistant-related mutations in TK gene represented frameshift mutations and single non-synonymous nucleotide substitutions of conserved gene regions. However, numerous amino acid changes could not be interpreted clearly as accounting for resistance. In conclusion, further studies, e.g. site-directed mutagenesis experiments are required to characterize mutations of the TK and DNA pol genes in ACV-resistant viral strains as part of viral gene polymorphism or as cause of drug resistance.
Assuntos
Aciclovir/farmacologia , Antivirais/farmacologia , Farmacorresistência Viral , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 1/fisiologia , Herpesvirus Humano 2/isolamento & purificação , Herpesvirus Humano 2/fisiologia , Aciclovir/análogos & derivados , Animais , Bromodesoxiuridina/análogos & derivados , Bromodesoxiuridina/farmacologia , Sobrevivência Celular , Células Cultivadas , Cidofovir , Citosina/análogos & derivados , Citosina/farmacologia , DNA Polimerase Dirigida por DNA/genética , Exodesoxirribonucleases/genética , Foscarnet/farmacologia , Guanina , Herpesvirus Humano 1/genética , Herpesvirus Humano 2/genética , Humanos , Testes de Sensibilidade Microbiana , Mutação de Sentido Incorreto , Organofosfonatos/farmacologia , Oxirredução , Análise de Sequência de DNA , Coloração e Rotulagem/métodos , Sais de Tetrazólio/metabolismo , Timidina Quinase/genética , Proteínas Virais/genéticaRESUMO
Varicella-zoster virus strains of European genotypes have developed a high variability of open reading frame (ORF) 62 during their occurrence over many years in Germany. M1 strains in Germany display a uniform ORF 62 pattern, suggesting that these strains were introduced from Africa and/or Asia via few sources during the last years.