Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
Center for Biomedical Research Support, The University of Texas at Austin, Austin, TX, USA.
Nat Commun. 2024 Oct 30;15(1):9403. doi: 10.1038/s41467-024-53658-8.
Mimicry of host protein structures, or 'molecular mimicry', is a common mechanism employed by viruses to evade the host's immune system. Short linear amino acid (AA) molecular mimics can elicit cross-reactive antibodies and T cells from the host, but the prevalence of such mimics throughout the human virome has not been fully explored. Here we evaluate 134 human-infecting viruses and find significant usage of linear mimicry across the virome, particularly those in the Herpesviridae and Poxviridae families. Furthermore, host proteins related to cellular replication and inflammation, autosomes, the X chromosome, and thymic cells are enriched as viral mimicry targets. Finally, we find that short linear mimicry from Epstein-Barr virus (EBV) is higher in auto-antibodies found in patients with multiple sclerosis than previously appreciated. Our results thus hint that human-infecting viruses leverage mimicry in the course of their infection, and that such mimicry may contribute to autoimmunity, thereby prompting potential targets for therapies.
宿主蛋白结构的模拟，或“分子模拟”，是病毒逃避宿主免疫系统的常见机制。短线性氨基酸 (AA) 分子模拟物可以从宿主中引发交叉反应性抗体和 T 细胞，但这种模拟物在人类病毒组中的普遍性尚未得到充分探索。在这里，我们评估了 134 种感染人类的病毒，发现病毒组中广泛存在线性模拟，特别是在疱疹病毒科和痘病毒科中。此外，与细胞复制和炎症、常染色体、X 染色体和胸腺细胞相关的宿主蛋白是病毒模拟物的富集靶点。最后，我们发现，与之前的认识相比，多发性硬化症患者自身抗体中发现的 EBV 短线性模拟物更高。因此，我们的研究结果表明，感染人类的病毒在其感染过程中利用模拟，并且这种模拟可能导致自身免疫，从而提示治疗的潜在靶点。
