Department of Anthropology, University of Massachusetts at Amherst, Amherst, Massachusetts, USA.
J Virol. 2013 Aug;87(15):8317-26. doi: 10.1128/JVI.01118-13. Epub 2013 Jun 5.
Due to inactivation of the α1,3-galactosyltransferase gene (GGTA1, or the α1,3GT gene) approximately 28 million years ago, the carbohydrate αGal (Galα1,3Galβ1,4GlcNAc) is not expressed on the cells of Old World monkeys and apes (including humans) but is expressed in all other mammals. The proposed selective advantage of this mutation for these primates is the ability to produce anti-Gal antibodies, which may be an effective immune component in neutralizing αGal-expressing pathogens. However, loss of α1,3GT expression may have been advantageous by providing natural resistance against viral pathogens that exploited the α1,3GT pathway or cell surface αGal for infection. Infections of paired cell lines with differential expression of α1,3GT showed that Sindbis viruses (SINV) preferentially replicate in α1,3GT-positive cells, whereas herpes simplex viruses type 1 and type 2 (HSV-1 and HSV-2) preferentially grow in cells lacking α1,3GT. Viral growth and spread correlated with the ability of the different viruses to successfully initiate infection in the presence or absence of α1,3GT expression. GT knockout (KO) suckling mice infected with SINV strains (AR339 and S.A.AR86) experienced significant delay in onset of disease symptoms and mortality compared to wild-type (WT) B6 suckling mice. In contrast, HSV-2-infected GT KO mice had higher viral titers in spleen and liver and exhibited significantly more focal hepatic necrosis than WT B6 mice. This study demonstrates that α1,3GT activity plays a role in the course of infections for certain viruses. Furthermore, this study has implications for the evolution of resistance to viral infections in primates.
大约 2800 万年前，由于α1,3-半乳糖基转移酶基因（GGTA1，即α1,3GT 基因）的失活，旧世界猴和猿（包括人类）的细胞不再表达碳水化合物αGal（Galα1,3Galβ1,4GlcNAc），但所有其他哺乳动物都表达αGal。这种突变对这些灵长类动物具有选择性优势，其原因是能够产生抗αGal 抗体，而这种抗体可能是中和表达αGal 的病原体的有效免疫成分。然而，α1,3GT 表达的丧失可能具有优势，因为它为自然抵抗利用 α1,3GT 途径或细胞表面αGal 进行感染的病毒病原体提供了天然抗性。对具有不同 α1,3GT 表达的配对细胞系进行感染表明，辛德毕斯病毒（SINV）优先在α1,3GT 阳性细胞中复制，而单纯疱疹病毒 1 型和 2 型（HSV-1 和 HSV-2）则优先在缺乏α1,3GT 的细胞中生长。病毒的生长和扩散与不同病毒在存在或不存在 α1,3GT 表达的情况下成功启动感染的能力相关。感染 SINV 株（AR339 和 S.A.AR86）的 GT 敲除（KO）乳鼠与野生型（WT）B6 乳鼠相比，疾病症状发作和死亡率显著延迟。相比之下，感染 HSV-2 的 GT KO 小鼠的脾脏和肝脏中的病毒滴度更高，并且肝坏死的焦点明显多于 WT B6 小鼠。本研究表明，α1,3GT 活性在某些病毒感染的过程中起作用。此外，本研究对灵长类动物对病毒感染的抗性进化具有重要意义。
