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Characterization of EIAV env Quasispecies during Long-Term Passage In Vitro: Gradual Loss of Pathogenicity

1
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150069, China
2
Key Laboratory of Special Animal Epidemic Disease of Ministry of Agriculture, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China
3
Department of Microbiology, Harbin Medical University, Harbin 150069, China
*
Authors to whom correspondence should be addressed.
These authors contribute equally to the work.
Viruses 2019, 11(4), 380; https://doi.org/10.3390/v11040380
Received: 15 February 2019 / Revised: 8 April 2019 / Accepted: 17 April 2019 / Published: 24 April 2019
(This article belongs to the Special Issue Nonprimate Lentivirus)
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Abstract

As the only widely used live lentiviral vaccine, the equine infectious anima virus (EIAV) attenuated vaccine was developed by in vitro passaging of a virulent strain for 121 generations. In our previous study, we observed that the attenuated vaccine was gradually selected under increased environmental pressure at the population level (termed a quasispecies). To further elucidate the potential correlation between viral quasispecies evolution and pathogenesis, a systematic study was performed by sequencing env using several methods. Some key mutations were identified within Env, and we observed that increased percentages of these mutations were accompanied by an increased passage number and attenuated virulence. Phylogenetic analysis revealed that env mutations related to the loss of virulence might have occurred evolutionarily. Among these mutations, deletion of amino acid 236 in the V4 region of Env resulted in the loss of one N-glycosylation site that was crucial for virulence. Notably, the 236-deleted sequence represented a “vaccine-specific” mutation that was also found in wild EIAVLN40 strains based on single genome amplification (SGA) analysis. Therefore, our results suggest that the EIAV attenuated vaccine may originate from a branch of quasispecies of EIAVLN40. Generally, the presented results may increase our understanding of the attenuation mechanism of the EIAV vaccine and provide more information about the evolution of other lentiviruses. View Full-Text
Keywords: EIAV; SGA (single genome amplification); quasispecies; virulence EIAV; SGA (single genome amplification); quasispecies; virulence
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Liu, C.; Wang, X.-F.; Wang, Y.; Chen, J.; Zhong, Z.; Lin, Y.; Wang, X. Characterization of EIAV env Quasispecies during Long-Term Passage In Vitro: Gradual Loss of Pathogenicity. Viruses 2019, 11, 380.

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