Koel Björn F, van der Vliet Stefan, Burke David F, Bestebroer Theo M, Bharoto Eny E, Yasa I Wayan W, Herliana Inna, Laksono Brigitta M, Xu Kemin, Skepner Eugene, Russell Colin A, Rimmelzwaan Guus F, Perez Daniel R, Osterhaus Albert D M E, Smith Derek J, Prajitno Teguh Y, Fouchier Ron A M
Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
JAPFA Comfeed, Indonesia.
mBio. 2014 Jun 10;5(3):e01070-14. doi: 10.1128/mBio.01070-14.
Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype are genetically highly variable and have diversified into multiple phylogenetic clades over the past decade. Antigenic drift is a well-studied phenomenon for seasonal human influenza viruses, but much less is known about the antigenic evolution of HPAI H5N1 viruses that circulate in poultry. In this study, we focused on HPAI H5N1 viruses that are enzootic to Indonesia. We selected representative viruses from genetically distinct lineages that are currently circulating and determined their antigenic properties by hemagglutination inhibition assays. At least six antigenic variants have circulated between 2003, when H5N1 clade 2.1 viruses were first detected in Indonesia, and 2011. During this period, multiple antigenic variants cocirculated in the same geographic regions. Mutant viruses were constructed by site-directed mutagenesis to represent each of the circulating antigenic variants, revealing that antigenic differences between clade 2.1 viruses were due to only one or very few amino acid substitutions immediately adjacent to the receptor binding site. Antigenic variants of H5N1 virus evaded recognition by both ferret and chicken antibodies. The molecular basis for antigenic change in clade 2.1 viruses closely resembled that of seasonal human influenza viruses, indicating that the hemagglutinin of influenza viruses from different hosts and subtypes may be similarly restricted to evade antibody recognition.
Highly pathogenic avian influenza (HPAI) H5N1 viruses are responsible for severe outbreaks in both commercial and backyard poultry, causing considerable economic losses and regular zoonotic transmissions to humans. Vaccination is used increasingly to reduce the burden of HPAI H5N1 virus in poultry. Influenza viruses can escape from recognition by antibodies induced upon vaccination or infection through genetic changes in the hemagglutinin protein. The evolutionary patterns and molecular basis of antigenic change in HPAI H5N1 viruses are poorly understood, hampering formulation of optimal vaccination strategies. We have shown here that HPAI H5N1 viruses in Indonesia diversified into multiple antigenic variants, that antigenic differences were due to one or a very few substitutions near the receptor binding site, and that the molecular basis for antigenic change was remarkably similar to that for seasonal human influenza viruses. These findings have consequences for future vaccination and surveillance considerations and contribute to the understanding of the antigenic evolution of influenza viruses.
H5N1亚型高致病性禽流感（HPAI）病毒在基因上具有高度变异性，在过去十年中已分化为多个系统发育分支。抗原漂移是季节性人流感病毒中一个研究充分的现象，但对于在家禽中传播的HPAI H5N1病毒的抗原进化了解较少。在本研究中，我们聚焦于在印度尼西亚呈地方流行的HPAI H5N1病毒。我们从当前正在传播的基因不同的谱系中选择代表性病毒，并通过血凝抑制试验确定其抗原特性。在2003年（印度尼西亚首次检测到H5N1 2.1分支病毒）至2011年期间，至少有六种抗原变体传播。在此期间，多种抗原变体在同一地理区域共同传播。通过定点诱变构建突变病毒以代表每种传播的抗原变体，结果显示2.1分支病毒之间的抗原差异仅归因于紧邻受体结合位点的一个或极少数氨基酸替换。H5N1病毒的抗原变体逃避了雪貂和鸡抗体的识别。2.1分支病毒抗原变化的分子基础与季节性人流感病毒极为相似，表明来自不同宿主和亚型的流感病毒血凝素可能同样受到限制以逃避抗体识别。
高致病性禽流感（HPAI）H5N1病毒导致商业和后院家禽的严重疫情，造成相当大的经济损失，并经常发生人畜共患病传播给人类。疫苗接种越来越多地用于减轻家禽中HPAI H5N1病毒的负担。流感病毒可通过血凝素蛋白的基因变化逃避疫苗接种或感染诱导产生的抗体的识别。HPAI H5N1病毒抗原变化的进化模式和分子基础了解甚少，这阻碍了最佳疫苗接种策略的制定。我们在此表明，印度尼西亚的HPAI H5N1病毒分化为多种抗原变体，抗原差异归因于受体结合位点附近的一个或极少数替换，并且抗原变化的分子基础与季节性人流感病毒非常相似。这些发现对未来疫苗接种和监测考量具有影响，并有助于理解流感病毒的抗原进化。
