Sharma Navita, Mishra Kamla Prasad, Chanda Sudipta, Bhardwaj Varun, Tanwar Himanshi, Ganju Lilly, Kumar Bhuvnesh, Singh Shashi Bala
Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Lucknow Road, Timarpur, New Delhi, Delhi, 110054, India.
O/o Director General (Life Sciences), Defence Research and Development Organization, New Delhi, 110011, India.
Arch Virol. 2019 Apr;164(4):1095-1110. doi: 10.1007/s00705-019-04179-z. Epub 2019 Feb 21.
Dengue disease is characterized by a marked decrease in platelet count, which is life threatening. In the present study, we investigated the antiviral activity of an aqueous extract of Carica papaya leaves (PLE) against dengue virus (DENV) and its effect on platelet augmentation. The anti-dengue activity of PLE in DENV-infected THP-1 cells was examined by immunoblotting and flow cytometry. The effect of PLE on erythrocyte damage was investigated using hemolytic and anti-hemolytic assays. Virus-infected THP-1 cells were assayed for IFN-α secretion. The effect of PLE on platelet augmentation in rats with cyclophosphamide-induced thrombocytopenia was also investigated. The platelet count of blood from the retro-orbital plexus of rats was determined on the 1, 4, 7, 11 and 14 day of study. On the 14 day, the rats were sacrificed for histopathological examination of the liver, kidney and spleen. Plasma of thrombocytopenic rats was tested for thrombopoietin (TPO) and IL-6 secretion. The data suggest that PLE significantly decreases the expression of the envelope and NS1 proteins in DENV-infected THP-1 cells. A marked decrease in intracellular viral load upon PLE treatment confirmed its antiviral activity. This also resulted in a significant decrease in erythrocyte damage and hydrogen-peroxide-induced lipid peroxidation. A significant increase in the number of platelets was found in thrombocytopenic rats treated with PLE, along with an increase in IL-6 and TPO levels. These findings suggest that PLE can potentially be used as an antiviral agent, as it helps in platelet augmentation and exhibits antiviral activity against DENV.
登革热疾病的特征是血小板计数显著下降，这会危及生命。在本研究中，我们调查了番木瓜叶水提取物（PLE）对登革热病毒（DENV）的抗病毒活性及其对血小板增加的影响。通过免疫印迹和流式细胞术检测了PLE在DENV感染的THP-1细胞中的抗登革热活性。使用溶血和抗溶血试验研究了PLE对红细胞损伤的影响。检测了病毒感染的THP-1细胞中IFN-α的分泌情况。还研究了PLE对环磷酰胺诱导的血小板减少症大鼠血小板增加的影响。在研究的第1、4、7、11和14天测定大鼠眶后丛血液中的血小板计数。在第14天，处死大鼠以进行肝脏、肾脏和脾脏的组织病理学检查。检测血小板减少症大鼠血浆中血小板生成素（TPO）和IL-6的分泌情况。数据表明，PLE显著降低了DENV感染的THP-1细胞中包膜蛋白和NS1蛋白的表达。PLE处理后细胞内病毒载量显著降低，证实了其抗病毒活性。这也导致红细胞损伤和过氧化氢诱导的脂质过氧化显著减少。在用PLE处理的血小板减少症大鼠中发现血小板数量显著增加，同时IL-6和TPO水平也增加。这些发现表明，PLE有可能用作抗病毒剂，因为它有助于血小板增加并对DENV表现出抗病毒活性。
