Lin Jie, Zhou Lei, Zhu Chenglin, Wei Jinhang, Lv Bo, Si Yuan, Zhu Shuangli, Ji Tianjiao, Wang Dongyan, Yang Qian, Xiao Jinbo, Yang Lan, Xiao Kaitao, Shao Kexin, Zhang Yong, Yan Dongmei
National Polio Laboratory, WHO WPRO Regional Polio Reference Laboratory, National Health Commission Key Laboratory for Biosecurity, National Health Commission Key Laboratory for Medical Virology, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
Microbiol Spectr. 2025 Sep 2;13(9):e0133425. doi: 10.1128/spectrum.01334-25. Epub 2025 Aug 8.
Since the establishment of the Chinese acute flaccid paralysis (AFP) case surveillance system in 1999, around 7,200 strains of poliovirus (PV) type 1 have been identified and isolated. Among these, the VP1 region of 5,649 strains has been sequenced. Based on the existing VP1 region sequence library, four strains of type 1 PV with six-nucleotide deletion in the VP1 region, identified from AFP cases, healthy children, and environmental sewage samples, were identified, and their biological characteristics were investigated. Whole-genome sequence analysis showed that the similarity with the Sabin 1 strain was 99.5-99.8%, and the mutation rate in the VP1 region was only 0.11-0.55%, indicating that these strains are not vaccine-derived PVs. The missing nucleotide is located at positions 2,783-2,788 in the VP1 region, resulting in the deletion of amino acids 102 and 103 at neutralizing antigen site 1 (N-Ag I) in the BC loop. It is worth noting that the neutralization test results showed that the two strains detected from AFP and healthy children evaded immune recognition, whereas the other two from environmental sewage did not. Molecular docking and neutralization antigen site analyzes indicate that the deletion of nucleotides 2,783-2,788 in N-Ag I is not a critical factor leading to the development of neutralization escape variants.IMPORTANCEInterestingly, we observed that the VP3-60 mutation in N-Ag IIIa may be the main reason for the immune evasion of these two viruses. In addition, based on the temperature sensitivity experiments, the four viruses exhibited similar temperature sensitivity to the Sabin 1 strain and their replication ability at 39.5°C was comparable to vaccine-derived polioviruses. Although variants with six-nucleotide deletion (2,783-2,788 nt) in the VP1 region do not cause significant biological changes, they can still spread in the environment and among populations, posing a certain risk of transmission.
自1999年中国急性弛缓性麻痹(AFP)病例监测系统建立以来,已鉴定并分离出约7200株1型脊髓灰质炎病毒(PV)。其中,5649株的VP1区域已进行测序。基于现有的VP1区域序列库,从AFP病例、健康儿童和环境污水样本中鉴定出4株在VP1区域有6个核苷酸缺失的1型PV,并对其生物学特性进行了研究。全基因组序列分析表明,它们与Sabin 1株的相似性为99.5%-99.8%,VP1区域的突变率仅为0.11%-0.55%,表明这些毒株不是疫苗衍生的PV。缺失的核苷酸位于VP1区域的2783-2788位,导致BC环中和抗原位点1(N-Ag I)的102和103位氨基酸缺失。值得注意的是,中和试验结果表明,从AFP病例和健康儿童中检测到的两株病毒逃避了免疫识别,而从环境污水中检测到的另外两株则没有。分子对接和中和抗原位点分析表明,N-Ag I中2783-2788位核苷酸的缺失不是导致中和逃逸变异体产生的关键因素。有趣的是,我们观察到N-Ag IIIa中的VP3-60突变可能是这两种病毒免疫逃逸的主要原因。此外,基于温度敏感性实验,这四种病毒对Sabin 1株表现出相似的温度敏感性,它们在39.5°C时的复制能力与疫苗衍生的脊髓灰质炎病毒相当。虽然VP1区域有6个核苷酸缺失(2783-2788 nt)的变异体不会引起显著的生物学变化,但它们仍可在环境和人群中传播,存在一定的传播风险。