H9N2亚型禽流感病毒HA蛋白S145N变异株致病性及抗原特性

为确定近年来H9N2亚型禽流感病毒(AIV) HA蛋白S145N点突变对病毒毒力变化和抗原性变异的影响,笔者对从全国不同地区分离的12株H9N2亚型AIV HA蛋白S145N变异株和HP疫苗参考株进行了半数鸡胚感染量(EID50)、半数鸡胚致死量(ELD50)、平均鸡胚致死时间(MDT)、雏鸡脑内致病指数(ICPI)、鸡静脉致病指数(IVPI)和8周龄SPF鸡感染排毒试验,并与抗H9N2亚型AIV HP参考株HA蛋白单抗2A4和F6的血凝抑制(HI)和中和反应特性进行测定.结果发现,H9N2亚型AIV HA蛋白S145N变异株毒力偏强,能引起部分SPF鸡发病和死亡,感染8周龄SPF鸡排毒时间更早,排毒期更长.单抗2A4和F6不能抑制H9N2亚型AIV HA蛋白S145N变异株的血凝特性,也不能中和病毒感染CEF细胞.研究结果表明,H9N2亚型AIV呈现变异趋势,有毒力增强和抗原性变异毒株出现.S145为H9N2亚型AIV HA蛋白的1个抗原位点,是血凝抑制抗体结合的位点,但有该位点漂变导致抗原变异毒株出现,并可逃避免疫作用.这提示该病的防控面临着新的挑战.

Characteristics of Pathogenic and Antigenic Variation of H9N2 Avian Influenza Viruses HA S145N Mutants in China

To investigate the effect of HA S145N mutation on pathogenicity and antigenicity of H9N2 avian influenza viruses(AIV),the EID50,ELD50,MDT,ICPI,IVPI and the duration of shedding virus from infected 8-week-old SPF chickens of different H9N2 AIV strains with HA S145N mutation isolated from Mainland China were determined.The HI and VN activity of monoclonal antibody 2A4 and F6 on different H9N2 AIV isolates were assayed.The determined pathogenicity suggested that the H9N2 AIVs with HA S145N mutation have higher pathogenicity and can cause the death of SPF chickens.The 8-week-old SPF chickens infected by H9N2 AIVs with HA S145N mutation shed virus earlier and last for a longer time.Monoclonal antibody 2A4 and F6 can inhibit the hemagglutinin activity of H9N2 AIVs with HA S145N mutation,however it can not neutralize the virus infection on CEF cells.The results showed that the H9N2 subtype AIVs have the tendency to evolve,resulting in the occurrence of mutants which have higher virulence and variable antigenicity.The site(S145) is one of HA protein epitope of the H9N2 subtype AIV.The higher virulent mutants may cause death of chickens and lead to more economic loss.The antigenic mutants may escape from immune clearance,which pose a new challenge to the immunoprophylaxis for the H9N2 avian influenza.