Gene mutations and molecular evolution of the chikungunya virus E1 and E2 from 2014 to 2019

Chikungunya virus (CHIKV), a mosquito-borne Alphavirus, is the etiological agent of chikungunya fever. To investigate the prevalence and genetic characteristics of CHIKV in China, we performed a molecular epidemiological study during the 2014-2019 period. Phylogenetic analysis of CHIKV in the 2014-2019 shows that it is currently clustered geographically, which means that CHIKVs local adaptability is gradually strengthening. Focusing on CHIKV adaptive mutation E1-A226V is not obvious in our study. The CHIKV E1 amino acid non-synonymous mutation results revealed the common mutation site M343I. Most mutation sites belong to the American epidemic strains, and the mutation rate is 2.8%. In 31 sequences, 19 non-synonymous mutations were found in CHIKV E1 (total mutation rate 20/499 = 4%), and 37 non-synonymous mutations in CHIKV E2 (total mutation rate 30/425 = 7%). It is worth noting that the mutation of CHIKV E2 has changed more than that of CHIKV E1 between 2014 and 2019. CHIKV E2 screened out common mutation sites, and the results showed that there are five common mutation sites, namely S119G, L182M, G206D, S300N, and A345T. Eighty-three percent of the CHIKV E2 receptor binding domain mutations in the American strains, namely T3I and N6H, may cause immune escape. We constructed a new luciferase immunosorbent assay using CHIKV E2 antigen and mutant E2 antigen to test the serum of the CHIKV infected patients, and the detected samples and dilution ratios were different. The T3I, N6H, S119G, L182M, G206D, S300N, and A345T mutations in CHIKV E2 could explain these differences between patients. IMPORTANCECHIKV originated in Africa more than 500 years ago, with a common lineage dividing into two distinct branches called West Africa (West African, WA) and East/Central/South Africa (East/Central/South African, ECSA). Moreover, the E1-A226V mutation enhanced the replication and transmission capacity of CHIKV in Aedes albopictus. However, it should be noted that E1-A226V does not explain the CHIKV epidemic that has occurred in the Americas in recent years. We analyzed CHIKV samples in the 2014-2019, and the results showed that the mutation of CHIKV E1 protein occurred was not mainly concentrated in E1-A226V, but concentrated in M343I. This also means that CHIKV constantly mutates in the natural environment and is formed under natural conditions. Analysis of the common mutation sites of CHIKV E2 showed that there were seven common mutation sites S119G/L182M/ G206D /S300N/A345T, and the new mutation of CHIKV E2 may affect serological antibody detection.