Boston College Biology Department, Chestnut Hill, Massachusetts.
Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts.
Endocrinology. 2019 Sep 1;160(9):2165-2179. doi: 10.1210/en.2019-00271.
Viruses have developed different mechanisms to manipulate their hosts, including the process of viral mimicry in which viruses express important host proteins. Until recently, examples of viral mimicry were limited to mimics of growth factors and immunomodulatory proteins. Using a comprehensive bioinformatics approach, we have shown that viruses possess the DNA/RNA with potential to encode 16 different peptides with high sequence similarity to human peptide hormones and metabolically important regulatory proteins. We have characterized one of these families, the viral insulin/IGF-1-like peptides (VILPs), which we identified in four members of the Iridoviridae family. VILPs can bind to human insulin and IGF-1 receptors and stimulate classic postreceptor signaling pathways. Moreover, VILPs can stimulate glucose uptake in vitro and in vivo and stimulate DNA synthesis. DNA sequences of some VILP-carrying viruses have been identified in the human enteric virome. In addition to VILPs, sequences with homology to 15 other peptide hormones or cytokines can be identified in viral DNA/RNA sequences, some with a very high identity to hormones. Recent data by others has identified a peptide that resembles and mimics α-melanocyte-stimulating hormone's anti-inflammatory effects in in vitro and in vivo models. Taken together, these studies reveal novel mechanisms of viral and bacterial pathogenesis in which the microbe can directly target or mimic the host endocrine system. These findings also introduce the concept of a system of microbial hormones that provides new insights into the evolution of peptide hormones, as well as potential new roles of microbial hormones in health and disease.
病毒已经开发出不同的机制来操纵它们的宿主，包括病毒模拟的过程，其中病毒表达重要的宿主蛋白。直到最近，病毒模拟的例子还仅限于生长因子和免疫调节蛋白的模拟物。我们使用全面的生物信息学方法，表明病毒具有 DNA/RNA 的潜力，可以编码 16 种不同的肽，这些肽与人肽激素和代谢重要的调节蛋白具有高度的序列相似性。我们已经描述了其中一种家族，即病毒胰岛素/IGF-1 样肽（VILP），我们在虹彩病毒科的四个成员中发现了这种肽。VILP 可以与人胰岛素和 IGF-1 受体结合，并刺激经典的受体后信号通路。此外，VILP 可以刺激体外和体内的葡萄糖摄取，并刺激 DNA 合成。一些携带 VILP 的病毒的 DNA 序列已在人类肠道病毒组中被识别。除了 VILP，还可以在病毒 DNA/RNA 序列中鉴定出与 15 种其他肽激素或细胞因子具有同源性的序列，其中一些与激素非常相似。其他人的最新数据已经确定了一种肽，它在体外和体内模型中类似于并模拟α-黑色素细胞刺激激素的抗炎作用。总之，这些研究揭示了病毒和细菌发病机制的新机制，其中微生物可以直接靶向或模拟宿主内分泌系统。这些发现还引入了微生物激素系统的概念，为肽激素的进化提供了新的见解，以及微生物激素在健康和疾病中的潜在新作用。
