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Attenuation of neurovirulence of chikungunya virus by a single amino acid mutation in viral E2 envelope protein.
- Source :
-
Journal of Biomedical Science . 1/17/2024, Vol. 31 Issue 1, p1-22. 22p. - Publication Year :
- 2024
-
Abstract
- Background: Chikungunya virus (CHIKV) has reemerged as a major public health concern, causing chikungunya fever with increasing cases and neurological complications. Methods: In the present study, we investigated a low-passage human isolate of the East/ Central/South African (ECSA) lineage of CHIKV strain LK(EH)CH6708, which exhibited a mix of small and large viral plaques. The small and large plaque variants were isolated and designated as CHIKV-SP and CHIKV-BP, respectively. CHIKV-SP and CHIKV-BP were characterized in vitro and in vivo to compare their virus production and virulence. Additionally, whole viral genome analysis and reverse genetics were employed to identify genomic virulence factors. Results: CHIKV-SP demonstrated lower virus production in mammalian cells and attenuated virulence in a murine model. On the other hand, CHIKV-BP induced higher pro-inflammatory cytokine levels, compromised the integrity of the blood–brain barrier, and led to astrocyte infection in mouse brains. Furthermore, the CHIKV-SP variant had limited transmission potential in Aedesalbopictus mosquitoes, likely due to restricted dissemination. Whole viral genome analysis revealed multiple genetic mutations in the CHIKV-SP variant, including a Glycine (G) to Arginine (R) mutation at position 55 in the viral E2 glycoprotein. Reverse genetics experiments confirmed that the E2-G55R mutation alone was sufficient to reduce virus production in vitro and virulence in mice. Conclusions: These findings highlight the attenuating effects of the E2-G55R mutation on CHIKV pathogenicity and neurovirulence and emphasize the importance of monitoring this mutation in natural infections. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10217770
- Volume :
- 31
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Biomedical Science
- Publication Type :
- Academic Journal
- Accession number :
- 174817689
- Full Text :
- https://doi.org/10.1186/s12929-024-00995-x