RESUMO
Chikungunya fever (CHIKF) is an acute febrile illness caused by a mosquito-borne alphavirus, chikungunya virus (CHIKV). This disease re-emerged in Kenya in 2004, and spread to the countries in and around the Indian Ocean. The re-emerging epidemics rapidly spread to regions like India and Southeast Asia, and it was subsequently identified in Europe in 2007, probably as a result of importation of chikungunya cases. On the one hand, chikungunya is one of the neglected diseases and has only attracted strong attention during large outbreaks. In 2008-2009, there was a major outbreak of chikungunya fever in Thailand, resulting in the highest number of infections in any country in the region. However, no update of CHIKV circulating in Thailand has been published since 2009. In this study, we examined the viral growth kinetics and sequences of the structural genes derived from CHIKV clinical isolates obtained from the serum specimens of CHIKF-suspected patients in Central Thailand in 2010. We identified the CHIKV harboring two mutations E1-A226V and E2-I211T, indicating that the East, Central, and South African lineage of CHIKV was continuously circulating as an indigenous population in Thailand.
Assuntos
Febre de Chikungunya/epidemiologia , Febre de Chikungunya/virologia , Vírus Chikungunya/isolamento & purificação , Vírus Chikungunya/classificação , Vírus Chikungunya/genética , Análise por Conglomerados , Variação Genética , Humanos , Modelos Moleculares , Epidemiologia Molecular , Dados de Sequência Molecular , Filogenia , Conformação Proteica , RNA Viral/genética , Análise de Sequência de DNA , Homologia de Sequência , Soro/virologia , Tailândia/epidemiologia , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genéticaRESUMO
The molecular basis of antibody neutralization against hepatitis C virus (HCV) is poorly understood. The E2 glycoprotein of HCV is critically involved in viral infectivity through specific binding to the principal virus receptor component CD81, and is targeted by anti-HCV neutralizing antibodies. A previous study showed that a mutation at position 534 (N534H) within the sixth N-glycosylation motif of E2 of the J6/JFH1 strain of HCV genotype 2a (HCV-2a) was responsible for more efficient access of E2 to CD81 so that the mutant virus could infect the target cells more efficiently. The purpose of this study was to analyze the sensitivity of the parental J6/JFH1, its cell culture-adapted variant P-47 possessing 10 amino acid mutations and recombinant viruses with the adaptive mutations to neutralization by anti-HCV antibodies in sera of HCV-infected patients. The J6/JFH1 virus was neutralized by antibodies in sera of patients infected with HCV-2a and -1b, with mean 50% neutralization titers being 1:670 and 1:200, respectively (P < 0.00001). On the other hand, the P-47 variant showed 50- to 200-times higher sensitivity to antibody neutralization than the parental J6/JFH1 without genotype specificity. The N534H mutation, and another one at position 416 (T416A) near the first N-glycosylation motif to a lesser extent, were shown to be responsible for the enhanced sensitivity to antibody neutralization. The present results suggest that the residues 534, and 416 to a lesser extent, of the E2 glycoprotein are critically involved in the HCV infectivity and antibody neutralization.
Assuntos
Hepacivirus/genética , Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/imunologia , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia , Motivos de Aminoácidos , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Linhagem Celular , Glicosilação , Hepacivirus/patogenicidade , Anticorpos Anti-Hepatite C/sangue , Humanos , Mutação PuntualRESUMO
Subacute sclerosing panencephalitis (SSPE) is a fatal neurodegenerative disease caused by prolonged persistent infection of the central nervous system with a measles virus (MV) mutant called SSPE virus. At present, there is no effective treatment to completely cure SSPE and development of a new therapeutic measure(s) against this fatal slow virus infection is needed. We previously reported that replication of MV and SSPE virus was effectively inhibited by small interfering RNA (siRNA), either chemically synthetic or plasmid-driven ones, that were targeted against different sequences of the mRNA for the L protein of MV. In this study, we have generated recombinant adenovirus expressing the siRNAs (rAd-siRNA-MV-L2, -L4 and -L5) and demonstrated that these rAd-siRNAs efficiently inhibited replication of MV and SSPE virus in a dose-dependent manner. Due to their high capacity for gene delivery to nerve cells and the potential to inhibit SSPE virus replication, the rAd-siRNAs could be a good candidate for a novel therapeutic measure against SSPE.