Russcher Anne, Mohammed Yassene, Kraakman Margriet E M, Chow Xavier, Kok Stijn T, Claas Eric C J, Wuhrer Manfred, Vossen Ann C T M, Kroes Aloys C M, de Vries Jutte J C
Medical Microbiology and Infection Control, Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center (LUMC), 2333 ZA Leiden, The Netherlands.
Center for Proteomics and Metabolomics, Leiden University Medical Center (LUMC), 2333 ZA Leiden, The Netherlands.
Viruses. 2025 Jul 23;17(8):1034. doi: 10.3390/v17081034.
Parvovirus B19 (B19V) can cause severe relapsing episodes of pure red cell aplasia in immunocompromised individuals, which are commonly treated with intravenous immunoglobulins (IVIGs). Few data are available on B19V intra-host evolution and the role of humoral immune selection. Here, we report the dynamics of genomic mutations and subsequent protein changes during relapsing infection.
Longitudinal plasma samples from immunocompromised patients with relapsing B19V infection in the period 2011-2019 were analyzed using whole-genome sequencing to evaluate intra-host evolution. The impact of mutations on the 3D viral protein structure was predicted by deep neural network modeling.
Of the three immunocompromised patients with relapsing infections for 3 to 9 months, one patient developed two consecutive nonsynonymous mutations in the VP1/2 region: T372S/T145S and Q422L/Q195L. The first mutation was detected in multiple B19V IgG-seropositive follow-up samples and resolved after IgG seroreversion. Computational prediction of the VP1 3D structure of this mutant showed a conformational change in the proximity of the antibody binding domain. No conformational changes were predicted for the other mutations detected.
Analysis of relapsing B19V infections showed mutational changes occurring over time. Resulting amino acid changes were predicted to lead to a conformational capsid protein change in an IgG-seropositive patient. The impact of humoral response and IVIG treatment on B19V infections should be further investigated to understand viral evolution and potential immune escape.
细小病毒B19（B19V）可在免疫功能低下的个体中引起严重的纯红细胞再生障碍性贫血复发，通常采用静脉注射免疫球蛋白（IVIG）进行治疗。关于B19V在宿主体内的进化以及体液免疫选择的作用，目前可用的数据很少。在此，我们报告复发性感染期间基因组突变及随后蛋白质变化的动态情况。
对2011年至2019年期间免疫功能低下的B19V复发性感染患者的纵向血浆样本进行全基因组测序分析，以评估宿主体内的进化情况。通过深度神经网络建模预测突变对3D病毒蛋白结构的影响。
在3名免疫功能低下且复发感染3至9个月的患者中，1名患者在VP1/2区域出现了两个连续的非同义突变：T372S/T145S和Q422L/Q195L。第一个突变在多个B19V IgG血清学阳性的随访样本中被检测到，并在IgG血清学转阴后消失。对该突变体的VP1 3D结构进行的计算预测显示，抗体结合域附近发生了构象变化。对检测到的其他突变未预测到构象变化。
对B19V复发性感染的分析显示，随着时间的推移会发生突变变化。预测所产生的氨基酸变化会导致一名IgG血清学阳性患者的衣壳蛋白构象发生变化。应进一步研究体液反应和IVIG治疗对B19V感染的影响，以了解病毒进化和潜在的免疫逃逸情况。
