Carvalho Valéria L, Nunes Márcio R T, da Silva Eliana V P, Vieira Conceição M A, Gomes Manoel, Casseb Samir M, Rodrigues Sueli G, Nunes-Neto Joaquim P, Quaresma Juarez A O, Vasconcelos Pedro F C
WHO Collaborating Center for Arbovirus Reference and Research, Department of Arbovirology and Hemorrhagic Fevers at Instituto Evandro Chagas, Ministry of Health, Belém, Pará State, Brazil.
J Gen Virol. 2009 Jan;90(Pt 1):223-33. doi: 10.1099/vir.0.002360-0.
Melao virus (MELV) strains BE AR8033 and BE AR633512 were isolated from pools of Ochlerotatus scapularis mosquitoes in Belém, Pará State (1955), and Alta Floresta, Rondônia State (2000), Brazil, respectively. The aim of the present study was to molecularly characterize these strains and to describe the histopathological, biochemical and immunological changes in golden hamsters (Mesocricetus auratus) following intraperitoneal injection of MELV strains. Hamsters were susceptible to both of the MELV strains studied. Viraemia was observed 3-6 days post-infection (p.i.) for BE AR633512 and only on the second day p.i. for BE AR8033. Neutralizing antibodies against both strains were detected in blood samples obtained at 5 days p.i. and persisted up to 30 days p.i. Aspartate aminotransferase, alanine aminotransferase and blood urea nitrogen were significantly altered in animals infected with the two MELV strains, while creatinine was only altered in animals inoculated with BE AR633512. Histopathological changes were observed in the central nervous system, liver, kidney and spleen of hamsters, and infection was confirmed by detection of specific MELV antigens by immunohistochemistry. Strain BE AR633512 caused more severe tissue damage than strain BE AR8033, showing increased neurovirulence and pathogenicity. Genetic analysis based on the full-length sequences of the glycoprotein (Gn and Gc) and nucleocapsid protein (N) genes revealed high levels of homology between the MELV strains. Interestingly, the greatest genetic divergence was found for the Gn gene of strain BE AR633512, in which several synonymous and non-synonymous mutations causing changes in RNA secondary structure were observed. Further studies will be necessary to investigate the role of Gn and Gc mutations in the MELV pathogenicity.
梅劳病毒（MELV）毒株BE AR8033和BE AR633512分别于1955年从巴西帕拉州贝伦市的肩突伊蚊群体中以及2000年从朗多尼亚州阿尔塔弗洛雷斯塔市的肩突伊蚊群体中分离得到。本研究的目的是对这些毒株进行分子特征分析，并描述金黄仓鼠（Mesocricetus auratus）腹腔注射MELV毒株后的组织病理学、生化和免疫学变化。仓鼠对所研究的两种MELV毒株均易感。感染BE AR633512后3 - 6天观察到病毒血症，而感染BE AR8033仅在感染后第二天观察到病毒血症。在感染后5天采集的血液样本中检测到针对两种毒株的中和抗体，并且这些抗体一直持续到感染后30天。感染两种MELV毒株的动物体内天冬氨酸转氨酶、丙氨酸转氨酶和血尿素氮均有显著变化，而肌酐仅在接种BE AR633512的动物体内发生变化。在仓鼠的中枢神经系统、肝脏、肾脏和脾脏中观察到组织病理学变化，并且通过免疫组织化学检测特异性MELV抗原证实了感染。毒株BE AR633512比毒株BE AR8033造成更严重的组织损伤，表现出更高的神经毒力和致病性。基于糖蛋白（Gn和Gc）和核衣壳蛋白（N）基因全长序列的遗传分析显示，MELV毒株之间具有高度同源性。有趣的是，在毒株BE AR633512的Gn基因中发现了最大的遗传差异，其中观察到几个导致RNA二级结构变化的同义突变和非同义突变。有必要进行进一步研究以调查Gn和Gc突变在MELV致病性中的作用。
