RESUMO
We report the molecular investigations of a large influenza A(H3N2) outbreak, in a season characterised by sharp increase in influenza admissions since December 2016. Analysis of haemagglutinin (HA) sequences demonstrated co-circulation of multiple clades (3C.3a, 3C.2a and 3C.2a1). Most variants fell into a novel subclade (proposed as 3C.2a2); they possessed four unique amino acid substitutions in the HA protein and loss of a potential glycosylation site. These changes potentially modify the H3N2 strain antigenicity.
Assuntos
Doenças Transmissíveis Emergentes/genética , Epidemias , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Hemaglutininas/genética , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , Criança , Pré-Escolar , Doenças Transmissíveis Emergentes/epidemiologia , Feminino , Deriva Genética , Variação Genética , Glicosilação , Humanos , Lactente , Recém-Nascido , Vírus da Influenza A Subtipo H3N2/classificação , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Influenza Humana/diagnóstico , Influenza Humana/virologia , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Filogenia , RNA Viral/genética , RNA Viral/isolamento & purificação , Análise de Sequência de DNA , Adulto JovemRESUMO
OBJECTIVES: To monitor HIV-1 integrase resistance mutations during raltegravir (RAL) therapy, including the impact of RAL interruption. DESIGN AND METHOD: An analysis of viral load and the HIV-1 integrase gene evolution in 26 HIV-1 treatment-experienced patients undergoing RAL therapy. RESULTS: Initial suppression of viral load was observed in all patients; however, four patients failed to maintain suppression and subsequently developed resistance at viral load rebound. Mutations Q148R (2 months) followed by G140A/Q148R and then G140A/Y143CHR/Q148R/G163R were detected in the virus from one patient, and these reverted to wild type when treatment was withdrawn, although clonal analysis identified maintenance of RAL resistance minority species at this time point. RAL treatment was restarted after 6 months, and 2 weeks later, Y143CY/G163RG mutations appeared. In three other patients, viruses with N155H emerged at viral rebound either alone (2 months), followed by V151I (8 months) or alone (10 months), or together with V151I/G163RG (7 months). Loss of virus with the N155H mutation occurred in these patients when RAL therapy was terminated, despite maintenance of reverse transcriptase/polymerase resistance mutations. CONCLUSION: Complete viral suppression was important in order to prevent resistance emerging. RAL-resistance mutations were detected in the presence of other antiviral treatments, and the reverse of these mutations following RAL cessation suggests that a fitness deficit was conferred by these mutants. The observation that following RAL interruption virus rebound was with previously existing reverse transcriptase/polymerase mutations in the absence of integrase mutations implies that it is pre-RAL-archived viruses that re-emerge.
