Malaria Molecular Epidemiology Unit, Malaria Translational Research Unit, Institut Pasteur du Cambodge, Institut Pasteur, Phnom Penh, Cambodia.
Center for Global Health and Diseases, Case Western Reserve University, School of Medicine, Cleveland, OH, 44106, USA.
Nat Commun. 2020 Feb 19;11(1):953. doi: 10.1038/s41467-020-14574-9.
Antigenic variation, the capacity to produce a range of variable antigens, is a well-described strategy of Plasmodium and other parasites to evade host immunity. Here, we show that gene amplification is an additional evasion mechanism used by Plasmodium vivax to escape humoral immunity targeting PvDBP, the key ligand involved in reticulocyte invasion. PvDBP gene amplification leads to increased mRNA levels and protects P. vivax in vitro against invasion inhibitory human monoclonal antibodies targeting a conserved binding domain of DBP. Patient samples suggest that parasites with increased pvdbp copy number are able to infect individuals with naturally acquired antibodies highly blocking the binding of PvDBP to the Duffy receptor. These results show that gene copy number variation affect the parasite's ability to evade anti-PvDBP humoral immunity.
抗原变异，即产生一系列变异抗原的能力，是疟原虫和其他寄生虫逃避宿主免疫的一种众所周知的策略。在这里，我们表明基因扩增是恶性疟原虫逃避针对 PfEMP1，即参与网织红细胞入侵的关键配体的体液免疫的另一种逃避机制。PfEMP1 基因扩增导致 mRNA 水平升高，并在体外保护恶性疟原虫免受针对 DBP 保守结合域的入侵抑制性人源单克隆抗体的侵袭。患者样本表明， PfEMP1 拷贝数增加的寄生虫能够感染自然获得的抗体高度阻断 PfEMP1 与 Duffy 受体结合的个体。这些结果表明基因拷贝数变异会影响寄生虫逃避抗 PfEMP1 体液免疫的能力。
