Bibliographic Details
| Title: |
Alternative splicing and genetic variation of mhc-e: implications for rhesus cytomegalovirus-based vaccines. |
| Authors: |
Brochu, Hayden, Wang, Ruihan, Tollison, Tammy, Pyo, Chul-Woo, Thomas, Alexander, Tseng, Elizabeth, Law, Lynn, Picker, Louis J., Gale Jr., Michael, Geraghty, Daniel E., Peng, Xinxia |
| Source: |
Communications Biology; 12/19/2022, Vol. 5 Issue 1, p1-13, 13p |
| Subject Terms: |
ALTERNATIVE RNA splicing, GENETIC variation, SIMIAN immunodeficiency virus, MACAQUES, VACCINES, RHESUS monkeys, T cells |
| Abstract: |
Rhesus cytomegalovirus (RhCMV)-based vaccination against Simian Immunodeficiency virus (SIV) elicits MHC-E-restricted CD8+ T cells that stringently control SIV infection in ~55% of vaccinated rhesus macaques (RM). However, it is unclear how accurately the RM model reflects HLA-E immunobiology in humans. Using long-read sequencing, we identified 16 Mamu-E isoforms and all Mamu-E splicing junctions were detected among HLA-E isoforms in humans. We also obtained the complete Mamu-E genomic sequences covering the full coding regions of 59 RM from a RhCMV/SIV vaccine study. The Mamu-E gene was duplicated in 32 (54%) of 59 RM. Among four groups of Mamu-E alleles: three ~5% divergent full-length allele groups (G1, G2, G2_LTR) and a fourth monomorphic group (G3) with a deletion encompassing the canonical Mamu-E exon 6, the presence of G2_LTR alleles was significantly (p = 0.02) associated with the lack of RhCMV/SIV vaccine protection. These genomic resources will facilitate additional MHC-E targeted translational research. The alternative splicing and genetic variations across the whole MHC-E locus of Rhesus Macaques (Mamu-E) are analysed, which provides a foundation for more comprehensive research of Mamu-E and informs translational research of CMV-based vaccines. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
