Since the initial detection in 2003, Indonesia has reported 200 human cases of highly pathogenic avian influenza H5N1 (HPAI H5N1), associated with an exceptionally high case fatality rate (84%) compared to other geographical regions affected by other genetic clades of the virus. However, there is limited information on the genetic diversity of HPAI H5N1 viruses, especially those isolated from humans in Indonesia. In this study, the genetic and antigenic characteristics of 35 HPAI H5N1 viruses isolated from humans were analyzed. Full genome sequences were analyzed for the presence of substitutions in the receptor binding site, and polymerase complex, as markers for virulence or human adaptation, as well as antiviral drug resistance substitutions. Only a few substitutions associated with human adaptation were observed, a remarkably low prevalence of the human adaptive substitution PB2-E627K, which is common during human infection with other H5N1 clades and a known virulence marker for avian influenza viruses during human infections. In addition, the antigenic profile of these Indonesian HPAI H5N1 viruses was determined using serological analysis and antigenic cartography. Antigenic characterization showed two distinct antigenic clusters, as observed previously for avian isolates. These two antigenic clusters were not clearly associated with time of virus isolation. This study provides better insight in genetic diversity of H5N1 viruses during human infection and the presence of human adaptive markers. These findings highlight the importance of evaluating virus genetics for HPAI H5N1 viruses to estimate the risk to human health and the need for increased efforts to monitor the evolution of H5N1 viruses across Indonesia.

自 2003 年首次发现以来，印度尼西亚报告了 200 例高致病性禽流感 H5N1 (HPAI H5N1) 人类病例，与受该病毒其他遗传分支影响的其他地理区域相比，病死率异常高 (84%)。然而，关于 HPAI H5N1 病毒的遗传多样性的信息有限，尤其是那些从印度尼西亚人类中分离出来的病毒。在这项研究中，分析了从人类中分离出的 35 种 HPAI H5N1 病毒的遗传和抗原特征。分析了全基因组序列中受体结合位点和聚合酶复合物的替代存在，作为毒力或人类适应的标记，以及抗病毒药物抗性替代。仅观察到与人类适应相关的少数替换，人类适应性替代 PB2-E627K 的流行率非常低，这在人类感染其他 H5N1 进化枝时很常见，也是人类感染期间禽流感病毒的已知毒力标志物。此外，这些印尼 HPAI H5N1 病毒的抗原谱是使用血清学分析和抗原图来确定的。抗原表征显示出两个不同的抗原簇，如先前对禽分离物所观察到的。这两个抗原簇与病毒分离的时间没有明显的关系。这项研究为人类感染期间 H5N1 病毒的遗传多样性和人类适应性标记的存在提供了更好的见解。