Marquine Solène, Briolant Sébastien, Claverie Damien, Denis Jessica, Geulen Manon, Bosio Laurent, Tenebray Bernard, Attoumani Sarah, Garnier Annabelle, Cheutin Laurence, Grard Gilda, Coutard Bruno, Durand Guillaume A, Badaut Cyril
Unité de Virologie, Institut de Recherche Biomédicale des Armées (IRBA), Marseille, France.
Unité des Virus Émergents (UVE: Aix-Marseille Univ, Università di Corsica, Inserm, France.
PLoS Negl Trop Dis. 2025 Jul 9;19(7):e0013274. doi: 10.1371/journal.pntd.0013274. eCollection 2025 Jul.
Due to their expanding geographical distribution, many orthoflaviviruses co-circulate, increasing the likelihood of serial infections in individuals living in endemic areas. The consequences of such infection histories remain poorly understood. Using a cohort of Zika virus-infected patients, we modeled the kinetics of individual humoral responses to Zika virus (ZIKV) infection. We compared them between patients with and without prior orthoflavivirus exposure. We determined the day the humoral response was maximal and the maximum amplitude. We then determined the characteristic values of specific and cross-reactive responses for each individual, whether previously infected with dengue virus (DENV) or not. ZIKV neutralization by sera from ZIKV-infected individuals was mainly attributable to virus-specific antibodies. However, the same sera were able to neutralize all four DENV serotypes. ZIKV neutralization by sera from patients with prior DENV infection was mainly due to cross-reactive antibodies, which were also able to seroneutralize all four DENV serotypes. The de-novo antibody response induced against ZIKV was masked by the anamnestic response against DENV. Overall, our results show that the humoral response to an orthoflavivirus infection is influenced by the patient's history of prior orthologous orthoflavivirus infections.
由于其地理分布不断扩大，许多正黄病毒共同传播，增加了流行地区居民发生连续感染的可能性。这种感染史的后果仍知之甚少。我们以一组寨卡病毒感染患者为对象，模拟了个体对寨卡病毒（ZIKV）感染的体液免疫反应动力学。我们比较了有和没有正黄病毒既往暴露史的患者之间的情况。我们确定了体液免疫反应达到最大值的日期和最大幅度。然后，我们确定了每个个体（无论之前是否感染过登革病毒（DENV））特异性和交叉反应性反应的特征值。寨卡病毒感染个体血清对寨卡病毒的中和作用主要归因于病毒特异性抗体。然而，相同的血清能够中和所有四种登革病毒血清型。既往感染过登革病毒的患者血清对寨卡病毒的中和作用主要是由于交叉反应性抗体，这些抗体也能够对所有四种登革病毒血清型进行血清中和。针对寨卡病毒诱导的从头抗体反应被针对登革病毒的回忆反应所掩盖。总体而言，我们的结果表明，对正黄病毒感染的体液免疫反应受患者既往同源正黄病毒感染史的影响。
