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<p>The Galα1-3Galβ1-4GlcNAc-R (αGal) epitope is found in all non-primate mammals, lemurs, and New World monkeys, but not in Old World monkeys, apes, or humans. Humans possess natural anti-αGal antibodies, which are hypothesized to prevent virus spillover through neutralization and complement-mediated inactivation of glycosylated viruses carried by animal hosts. Low or absent titers of anti-αGal antibodies are found in newborns and certain populations, leading to a reduced natural antibody-mediated immune barrier. The expression of αGal in animal reservoirs of coronaviruses remains unclear. Surprisingly, the <i>α-1</i>,<i>3-galactosyltransferase (α1</i>,<i>3GT)</i> gene in pangolins is classified as inactive according to the National Center for Biotechnology Information (NCBI) Reference Sequence: XM_036915461.1. In this study, we cloned the α1,3GT family from animal reservoirs of coronaviruses and investigated its ability to modify surface glycoproteins of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) pseudovirus. The results showed that the bat and pangolin genomes contain functional <i>α1</i>,<i>3GT1</i> and <i>α1</i>,<i>3GT2</i> genes. The bat α1,3GT1 can catalyze the expression of the αGal epitope on SARS-CoV-2 envelope glycoproteins. Anti-αGal antibodies neutralized SARS-CoV-2 pseudoviruses packaged in glycoengineered 293T cells expressing the αGal epitopes. Our findings reveal the presence of functional <i>α1</i>,<i>3GT</i>s in animal reservoirs of coronaviruses, which may be exploited as a target for natural antibody neutralization to prevent virus spillover.</p>

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Genetic Basis of α-1,3 Galactose Epitopes in Animal Reservoirs of Coronaviruses

  • 期刊论文

  • 发表日期：

    2026年5月7日

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  • Xinjia Mai,
  • Chenxi Zhu,
  • Yu He,
  • Nian Wang,
  • Yue Ma,
  • Wen Zhang,
  • Yanping Wang,
  • Yunsen Li,
  • Dapeng Zhou

摘要

The Galα1-3Galβ1-4GlcNAc-R (αGal) epitope is found in all non-primate mammals, lemurs, and New World monkeys, but not in Old World monkeys, apes, or humans. Humans possess natural anti-αGal antibodies, which are hypothesized to prevent virus spillover through neutralization and complement-mediated inactivation of glycosylated viruses carried by animal hosts. Low or absent titers of anti-αGal antibodies are found in newborns and certain populations, leading to a reduced natural antibody-mediated immune barrier. The expression of αGal in animal reservoirs of coronaviruses remains unclear. Surprisingly, the α-1,3-galactosyltransferase (α1,3GT) gene in pangolins is classified as inactive according to the National Center for Biotechnology Information (NCBI) Reference Sequence: XM_036915461.1. In this study, we cloned the α1,3GT family from animal reservoirs of coronaviruses and investigated its ability to modify surface glycoproteins of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) pseudovirus. The results showed that the bat and pangolin genomes contain functional α1,3GT1 and α1,3GT2 genes. The bat α1,3GT1 can catalyze the expression of the αGal epitope on SARS-CoV-2 envelope glycoproteins. Anti-αGal antibodies neutralized SARS-CoV-2 pseudoviruses packaged in glycoengineered 293T cells expressing the αGal epitopes. Our findings reveal the presence of functional α1,3GTs in animal reservoirs of coronaviruses, which may be exploited as a target for natural antibody neutralization to prevent virus spillover.