Humans are infected with paramyxoviruses of different genera early in life, which induce cytotoxic T cells that may recognize conserved epitopes. This raises the question of whether cross-reactive T cells induced by antecedent paramyxovirus infections provide partial protection against highly lethal zoonotic Nipah virus infections. By characterizing a measles virus-specific but paramyxovirus cross-reactive human T cell clone, we discovered a highly conserved HLA-B*1501-restricted T cell epitope in the fusion protein. Using peptides, tetramers, and single cell sorting, we isolated a parainfluenza virus-specific T cell clone from a healthy adult and showed that both clones cleared Nipah virus-infected cells. We identified multiple conserved hot spots in paramyxovirus proteomes that contain other potentially cross-reactive epitopes. Our data suggest that, depending on HLA haplotype and history of paramyxovirus exposures, humans may have cross-reactive T cells that provide protection against Nipah virus. The effect of preferential boosting of these cross-reactive epitopes needs to be further studied in light of paramyxovirus vaccination studies.IMPORTANCE Humans encounter multiple paramyxoviruses early in life. This study shows that infection with common paramyxoviruses can induce T cells cross-reactive with the highly pathogenic Nipah virus. This demonstrates that the combination of paramyxovirus infection history and HLA haplotype affects immunity to phylogenetically related zoonotic paramyxoviruses.

, , , ,,
Erasmus MC: University Medical Center Rotterdam

de Vries, R.D, de Jong, A. (Alwin), Verburgh, R.J, Sauerhering, L. (Lucie), van Nierop, G.P, van Binnendijk, R.S, … de Swart, R.L. (2020). Human Paramyxovirus Infections Induce T Cells That Cross-React with Zoonotic Henipaviruses. mBio, 11(4). doi:10.1128/mBio.00972-20