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

Authors

Dhiraj Acharya, University of Southern MississippiFollow
Amber M. Paul, University of Southern MississippiFollow
John F. Anderson, Connecticut Agricultural Experiment StationFollow
Faqing Huang, University of Southern MississippiFollow
Fengwei Bai, University of Southern MississippiFollow

Document Type

Article

Publication Date

10-20-2015

Department

Biological Sciences

School

Biological, Environmental, and Earth Sciences

Abstract

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 (CHIKV_mos) has slower replication than mammalian cell-derived CHIKV (CHIKV_vero), when tested in both human and murine cell lines. Consistent with this, CHIKV_mos infection in both cell lines produce less cytopathic effects and reduced antiviral responses. In addition, infection in mice show that CHIKV_mos produces a lower level of viremia and less severe footpad swelling when compared with CHIKV_vero. Interestingly, CHIKV_mos 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. Moreover, CHIKV_mos progenies can regain GAG receptor binding capability and can replicate similarly to CHIKV_vero after a single passage in mammalian cells. Furthermore, CHIKV_vero and CHIKV_mos 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.

Publication Title

PLOS Neglected Tropical Diseases

Volume

9

First Page

1

Last Page

31

Recommended Citation

Acharya, D., Paul, A. M., Anderson, J. F., Huang, F., Bai, F. (2015). Loss of Glycosaminoglycan Receptor Binding After Mosquito Cell Passage Reduces Chikungunya Virus Infectivity. PLOS Neglected Tropical Diseases, 9, 1-31.
Available at: https://aquila.usm.edu/fac_pubs/15119