RESUMO
Among a panel of 788 clinical influenza H3N2 isolates, two isolates were characterized by an oseltamivir-resistant phenotype linked to the absence of any detectable NA activity. Here, we established that the two H3NA- isolates lack any detectable full-length NA segment, and one of these could be rescued by reverse genetics in the absence of any NA segment sequence. We found that the absence of NA segment induced a moderate growth defect of the H3NA- viruses as on cultured cells. The glycoproteins density at the surface of H3NA- virions was unchanged as compared to H3N2 virions. The HA protein as well as residues 188 and 617 of the PB1 protein were shown to be strong determinants of the ability of H3NA- viruses to grow in the absence of the NA segment. The significance of these findings about naturally occurring seven-segment influenza A viruses is discussed.
Assuntos
Vírus da Influenza A/genética , Neuraminidase/genética , Replicação Viral/fisiologia , Sequência de Aminoácidos , Animais , Antivirais/farmacologia , Linhagem Celular , Microscopia Crioeletrônica , Cães , Farmacorresistência Viral/genética , Inibidores Enzimáticos/farmacologia , Regulação Enzimológica da Expressão Gênica , Regulação Viral da Expressão Gênica/fisiologia , Humanos , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/enzimologia , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/enzimologia , Vírus da Influenza A/fisiologia , Modelos Moleculares , Neuraminidase/antagonistas & inibidores , Neuraminidase/química , Oseltamivir/farmacologia , Conformação Proteica , Alinhamento de Sequência , Vírion/ultraestruturaRESUMO
BACKGROUND: Respiratory infections caused by viruses are major causes of upper and lower respiratory tract infections. They account for an important mortality and morbidity worldwide. Amongst these viruses, influenza viruses and paramyxoviruses are major pathogens. Their transmission is mainly airborne, by direct transmission through droplets from infected cases. OBJECTIVES: In the context of an influenza pandemic, as well as for the reduction of nosocomial infections, systems that can reduce or control virus transmission will reduce the burden of this disease. It may also be part of the strategy for pandemic mitigation. STUDY DESIGN: A new system based on physical decontamination of surface and air has been developed. This process generates cold oxygen plasma (COP) by subjecting air to high-energy deep-UV light. To test its efficiency, we have developed an experimental device to assess for the decontamination of nebulized respiratory viruses. High titer suspensions of influenza virus type A, human parainfluenza virus type 3 and RSV have been tested. RESULTS: Different experimental conditions have been evaluated against these viruses. The use of COP with an internal device allowed the best results against all viruses tested. We recorded a reduction of 6.5, 3.8 and 4 log(10) TCID50/mL of the titre of the hPIV-3, RSV and influenza virus A (H5N2) suspensions. CONCLUSIONS: The COP technology is an efficient and innovative strategy to control airborne virus dissemination. It could successfully control nosocomial diffusion of respiratory viruses in hospital setting, and could be useful for the reduction of influenza transmission in the various consultation settings implemented for the management of cases during a pandemic.