Loss of Glycosaminoglycan Receptor Binding after Mosquito Cell Passage Reduces Chikungunya Virus Infectivity

被引:25
作者
Acharya, Dhiraj [1 ]
Paul, Amber M. [1 ]
Anderson, John F. [2 ]
Huang, Faqing [3 ]
Bai, Fengwei [1 ]
机构
[1] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA
[2] Connecticut Agr Expt Stn, Dept Entomol, New Haven, CT 06504 USA
[3] Univ So Mississippi, Dept Chem & Biochem, Hattiesburg, MS 39406 USA
关键词
SEMLIKI-FOREST-VIRUS; HEPARAN-SULFATE BINDING; ROSS RIVER VIRUS; DENGUE-VIRUS; E2; GLYCOPROTEIN; SINDBIS VIRUS; ENCEPHALITIS-VIRUS; DC-SIGN; VIRULENCE ATTENUATION; CULTURED MOSQUITO;
D O I
10.1371/journal.pntd.0004139
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that can cause fever and chronic arthritis in humans. CHIKV that is generated in mosquito or mammalian cells differs in glycosylation patterns of viral proteins, which may affect its replication and virulence. Herein, we compare replication, pathogenicity, and receptor binding of CHIKV generated in Vero cells (mammal) or C6/36 cells (mosquito) through a single passage. We demonstrate that mosquito cell-derived CHIKV (CHIKVmos) has slower replication than mammalian cell-derived CHIKV (CHIKVvero), when tested in both human and murine cell lines. Consistent with this, CHIKVmos infection in both cell lines produce less cytopathic effects and reduced antiviral responses. In addition, infection in mice show that CHIKVmos produces a lower level of viremia and less severe footpad swelling when compared with CHIKVvero. Interestingly, CHIKVmos has impaired ability to bind to glycosaminoglycan (GAG) receptors on mammalian cells. However, sequencing analysis shows that this impairment is not due to a mutation in the CHIKV E2 gene, which encodes for the viral receptor binding protein. More-over, CHIKVmos progenies can regain GAG receptor binding capability and can replicate similarly to CHIKVvero after a single passage in mammalian cells. Furthermore, CHIKVvero and CHIKVmos no longer differ in replication when N-glycosylation of viral proteins was inhibited by growing these viruses in the presence of tunicamycin. Collectively, these results suggest that N-glycosylation of viral proteins within mosquito cells can result in loss of GAG receptor binding capability of CHIKV and reduction of its infectivity in mammalian cells.
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页数:31
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