Abstract：
Merozoites utilize sialic acids on the red blood cell (RBC) cell surface to rapidly adhere to and invade the RBCs. Newcastle disease virus (NDV) displays a strong affinity toward membrane-bound sialic acids. Incubation of NDV with the malaria parasites dose-dependently reduces its cellular viability. The antiplasmodial activity of NDV is specific, as incubation with Japanese encephalitis virus, duck enteritis virus, infectious bronchitis virus, and influenza virus did not affect the parasite propagation. Interestingly, NDV is reducing more than 80% invasion when RBCs are pretreated with the virus. Removal of the RBC surface proteins or the NDV coat proteins results in disruption of the virus binding to RBC. It suggests the involvement of specific protein: ligand interaction in virus binding. We established that the virus engages with the parasitized RBCs (PRBCs) through its hemagglutinin neuraminidase (HN) protein by recognizing sialic acid-containing glycoproteins on the cell surface. Blocking of the HN protein with free sialic acid or anti-HN antibodies abolished the virus binding as well as its ability to reduce parasite growth. Interestingly, the purified HN from the virus alone could inhibit the parasite\'s growth in a dose-dependent manner. NDV binds strongly to knobless murine parasite strain Plasmodium yoelii and restricted the parasite growth in mice. Furthermore, the virus was found to preferentially target the PRBCs compared to normal erythrocytes. Immunolocalization studies reveal that NDV is localized on the plasma membrane as well as weakly inside the PRBC. NDV causes neither any infection nor aggregation of the human RBCs. Our findings suggest that NDV is a potential candidate for developing targeted drug delivery platforms for the Plasmodium-infected RBCs.
摘要：
孢子利用红细胞(RBC)细胞表面上的唾液酸快速粘附并侵入RBC。新城疫病毒（NDV）对膜结合的唾液酸具有很强的亲和力。NDV与疟疾寄生虫的孵育剂量依赖性地降低其细胞活力。NDV的抗疟药活性是特异性的，与日本脑炎病毒一起孵化，鸭肠炎病毒,传染性支气管炎病毒，流感病毒并不影响寄生虫的繁殖。有趣的是,当用病毒预处理RBC时,NDV减少超过80%的侵袭。去除RBC表面蛋白或NDV外壳蛋白导致病毒与RBC结合的破坏。这表明特定蛋白质：配体相互作用参与病毒结合。我们确定，该病毒通过识别细胞表面含唾液酸的糖蛋白，通过其血凝素神经氨酸酶（HN）蛋白与寄生的红细胞（PRBC）结合。用游离唾液酸或抗HN抗体阻断HN蛋白消除了病毒结合以及其减少寄生虫生长的能力。有趣的是,单独从病毒中纯化的HN可以以剂量依赖的方式抑制寄生虫的生长。NDV与无节诺鼠寄生虫菌株约氏疟原虫强烈结合，并限制了小鼠的寄生虫生长。此外，与正常红细胞相比,发现该病毒优先靶向PRBC.免疫定位研究表明，NDV位于质膜上以及PRBC内部。NDV既不引起任何感染也不引起人RBC的聚集。我们的研究结果表明，NDV是开发针对疟原虫感染的红细胞的靶向药物递送平台的潜在候选者。
