E2 and Erns of classical swine fever virus C-strain play central roles in its adaptation to rabbits
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The classical swine fever virus (CSFV) C-strain has been used as a vaccine strain for over 60 years in China. A recent study has demonstrated that the E2 protein of C-strain plays a major role in its adaptation to rabbits. E2 protein in combination with either Erns or E1 confers rabbit adaptation for the C-strain, and the residues P108 and T109 in domain I of E2 are critical for rabbit adaptation. To further identify the contributions of the glycoproteins to rabbit adaptation, a series of C-strain-based chimeric viruses containing single or double glycoprotein substitutions of the Shimen strain were generated and inoculated into rabbits. Profiles of rectal temperature, viral RNA, E2 protein expression, and antibody responses were compared among the chimeric viruses. Replacement of Erns, E2, Erns–E2, or E1–E2 of the C-strain with the counterpart(s) of the Shimen strain led to decreased fever response, reduction of viral RNA and antibody responses in rabbits, as compared with their parental C-strain. The C-strain-based chimeric virus expressing the Shimen strain E1 exhibited typical fever response and viral RNA level similar to the C-strain. However, substitution of both Erns and E2 in the C-strain backbone abolished fever response, and the chimeric virus did not show adaptation in rabbits as demonstrated by lack of viral RNA and E2 protein expression in the spleen and weak antibody responses. These results indicate that Erns has partial contribution to adaptation of the C-strain in rabbits, and combination of E2 and Erns is essential for the C-strain to have adaptive replication in rabbits.
KeywordsClassical swine fever virus C-strain Glycoproteins Rabbit adaptation
This study is part of the work sponsored by the Special Funding for Doctoral Programs at Institutions of High Learning, Chinese Ministry of Education (20120101130014) and Dabeinong Funds for Discipline Development and Talent Training in Zhejiang University, and Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai, China (KLAB201711).
TC, XL, and WF designed the experiments. TC, ZW, XL, SZ, and XZ performed the experiments. TC and WF analyzed the data and designed the figures. TC, NP, and WF wrote the manuscript. All authors read and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
All the authors declare no conflict of interest.
Animal experiments were conducted following the guidelines and approved protocols of the Laboratory Animal Management Committee of Zhejiang University, China (Approval number: ZJU20180766).
All authors read and approved the manuscript.
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