中文摘要：

目的 探索季节性流感病毒H1N1和H3N2疫苗株在BALB/c小鼠中传代适应的可能性.方法 将2008-2009年度季节性流感病毒疫苗株滴鼻感染BALB/c小鼠,在病毒增殖高峰期取肺组织制备肺悬液,连续传代10代,并对野生型与鼠肺适应株在小鼠中的致死性与全基因组序列进行比较.结果 H3N2疫苗株感染BALB/c小鼠后均未在肺部检测到病毒;而H1N1疫苗株感染小鼠后第2天为病毒生长高峰期,病毒滴度随传代次数的增加而升高;全基因组序列分析结果表明HA-N142D突变与病毒毒力的的提高密切相关.结论 H3N2疫苗株难以在BALB/c小鼠中有效复制与适应;而H1N1疫苗株能够在BALB/c小鼠中有效复制,其毒力可以通过连续的鼠肺传代而提高,HA-N142D突变对H1N1疫苗株致病性的增加密切相关,为进一步研究流感病毒鼠肺适应的分子机理奠定了基础.

英文摘要：

Objective To investigate the possibility of adaptation seasonal influenza virus H1N1 and H3N2 vaccine strains in BALB/C mice.Methods BALB/c mice were infected with wild-type virus and lungs were dissected out at peak of virus multiplication to generate the first passage of mouse adapted virus （P1）,which was subjected serial mouse lung-to-lung passages （from P1 to P10）.Pathogenicity and genome sequences of wide-type and mouse-adapted virus were compared.Results For H3N2 vaccine strain,virus titer was under detection at any passages.In contrast,for H1N1 vaccine strain,virus replication ability and pathogenicity increased by lung-to-lung passage.Genome sequence analysis of H1Nlwt and H1N1MA indicated that mutation of HA-N142D contributed to the enhanced virulence.Conclusions H3N2 vaccine strain was difficult to replicate in mice while H1 N1 vaccine strain could effectively replicate in BALB/c mice and mutation of HA-N142D contributed to the enhanced virulence.