Autor(es): Acharya Dhiraj, Paul Amber M, Anderson John F, Huang Faqing, Bai Fengwei

Resumo: Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that can cause fever - 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 - virulence. Herein, we compare replication, pathogenicity, - 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 - murine cell lines. Consistent with this, CHIKV mos infection in both cell lines produce less cytopathic effects - reduced antiviral responses. In addition, infection in mice show that CHIKV mos produces a lower level of viremia - 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 - can replicate similarly to CHIKV vero after a single passage in mammalian cells. Furthermore, CHIKV vero - 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 - reduction of its infectivity in mammalian cells.

Imprenta: PLoS Neglected Tropical Diseases, v. 9, n. 10, p. e0004139, 2015

Identificador do objeto digital: 10.1371/journal.pntd.0004139

Descritores: Chikungunya virus - Biochemistry ; Chikungunya virus - Cell ; Chikungunya virus - Proteins ; Chikungunya Virus - Virus ; Chikungunya virus - Chikungunya fever

Data de publicação: 2015