Abstract
It has been observed that replication of Chikungunya virus (CHIKV) in C6/36 Aedes albopictus cells has little effect on virus evolution. To characterize evolutionary patterns associated with CHIKV replication in mosquito cells, we performed serial passages of the LR2006 strain in Ae. albopictus cells (75 and 30 passages in C6/36 and U4.4 respectively) and Ae. aegypti cells (100 passages in AA-A20 and in AE) and studied genotypic changes accompanying adaptation during this evolutionary process. Quantitative analysis revealed cell specific patterns: low mutation rates in C6/36 cells except when a CHIKV strain pre-adapted to mammalian was used and typical features of adaptation to cell culture conditions with a high number of fixed mutations in AE and AA-A20 cells probably due to the weak permissiveness of these latter cell lines. Altogether, these results suggested that both cell line and viral strain influence rates of viral evolution. In contrast, characteristics and distribution of mutations were qualitatively very similar in all mosquito cells with a high level of parallel evolution including 4 deletion mutations. Serial passage in mammalian cells of viruses pre-adapted to mosquito cells revealed disappearance of almost all shared mutations suggesting that many of these mutational patterns are vector-specific.
Highlights
RNA viruses are characterized by high mutation rates[1,2,3]
These studies revealed general patterns of arbovirus evolution: (i) most of the time, adaptation of the virus to a single host resulted in a fitness gain in the same environment[18], (ii) observation of fitness trade-offs was unpredictable and sometimes fitness trade-offs were asymmetrical[10,11,12,13,14,15,16,17], (iii) alternation between vector and host cells generally resulted in fitness increases in one or both vector/host cells[10,11,12,13,14,15,16,17]
When working with arboviruses transmitted by mosquitoes such as dengue virus, eastern equine encephalitis virus, Sindbis virus or chikungunya virus (CHIKV), it was often observed that the rate of mutation accumulation was slower when viruses were serially passaged in mosquito cells suggesting that replication in mosquito
Summary
RNA viruses are characterized by high mutation rates[1,2,3]. Mutations are frequently incorporated during viral RNA replication due to low fidelity of the viral RNA dependent RNA polymerase (RdRP) and the inability to correct errors[4]. Arboviruses were serially passaged either in vertebrate or arthropod cells or in each cell line alternately to simulate the natural cycle of the virus and the fitness of progeny viruses was assessed relative to progenitors These studies revealed general patterns of arbovirus evolution: (i) most of the time, adaptation of the virus to a single host resulted in a fitness gain in the same environment[18], (ii) observation of fitness trade-offs (i.e. adaption to vector/host cells resulting in loss of fitness in the bypassed host/vector cells) was unpredictable and sometimes fitness trade-offs were asymmetrical[10,11,12,13,14,15,16,17], (iii) alternation between vector and host cells generally resulted in fitness increases in one or both vector/host cells[10,11,12,13,14,15,16,17]. When working with arboviruses transmitted by mosquitoes such as dengue virus, eastern equine encephalitis virus, Sindbis virus or chikungunya virus (CHIKV), it was often observed that the rate of mutation accumulation was slower when viruses were serially passaged in mosquito cells suggesting that replication in mosquito www.nature.com/scientificreports/
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