Dysfunction of Complementarity Determining Region 1 Encoded by T Cell Receptor Beta Variable Gene Is Potentially...

Area of Science:

• Immunogenetics
• Comparative genomics
• Veterinary virology

Background:

• The beta T-cell receptor (TRB) is crucial for recognizing foreign antigens via its complementarity determining regions (CDRs).
• African suids naturally lack a specific segment in the TRBV27 gene encoding CDR1, unlike domestic pigs.
• The functional significance of this TRBV27-encoded CDR1 in pathogen resistance remains unclear.

Purpose of the Study:

• To investigate the impact of deleting the TRBV27-encoded CDR1 sequence on domestic pigs' resistance to African swine fever virus (ASFV).
• To utilize CRISPR/Cas9 gene-editing technology to create pigs with a disrupted TRBV27 CDR1 sequence.

Main Methods:

• Generated TRBV27-edited fibroblasts using CRISPR/Cas9 technology.
• Produced gene-edited pigs via somatic cell nuclear transfer from edited fibroblasts.
• Infected both gene-edited and wild-type pigs with ASFV for comparative analysis.

Main Results:

• TRBV27-edited pigs exhibited reduced white blood cell counts prior to infection.
• Both edited and wild-type pigs were susceptible to ASFV, showing fever and mortality within 10 days.
• Gene-edited pigs displayed higher viral loads and more severe clinical signs compared to wild-type controls.

Conclusions:

• Deletion of the TRBV27-encoded CDR1 sequence in pigs does not confer resistance to ASFV.
• The absence of TRBV27 CDR1 may increase susceptibility to ASFV infection.
• Further research with attenuated ASFV strains is recommended to explore long-term effects and host-pathogen interactions.