Pöhlmann Stefan, Krüger Astrid, Hafezi Wali, Schneider Stefan, Gruber Jens, Winkler Michael, Kaul Artur
Infection Biology Unit, German Primate Center, 37077 Göttingen, Germany.
Department of Medical Microbiology, University of Münster, 48149 Münster, Germany.
Primate Biol. 2017 Feb 17;4(1):9-16. doi: 10.5194/pb-4-9-2017. eCollection 2017.
Herpes B virus (BV) infection is highly prevalent among adult Asian macaques and rarely causes severe disease in infected animals. In contrast, BV infection of humans can induce fatal encephalitis in the absence of treatment. Therefore, the development of diagnostic tests for specific and sensitive detection of antibodies against BV is an important task. The cross-reactivity of antibodies against BV with related simplex viruses of other primates may afford an opportunity to obtain sensitive detection systems without the need to work with the highly pathogenic BV. Moreover, it has been proposed that use of recombinant viral glycoproteins may allow for a detection of antibody responses against BV with high specificity. However, limited data are available for both approaches to BV diagnostic. Here, we report that simian agent 8 (SA8; infects African green monkeys)- and herpesvirus papio 2 (HVP-2; infects baboons)-infected cells allow for a more sensitive detection of antibody responses against BV in macaques than lysates of herpes simplex virus type 1 and 2 (HSV-1/2; infect humans)-infected cells and a commercial HSV ELISA (Enzygnost Anti-HSV/IgG). In addition, we show that sera from BV-infected macaques frequently contain antibodies against the recombinant BV glycoprotein gD (BV gD) that has been previously proposed as a diagnostic target for discriminating BV- and HSV-induced antibodies. However, we found that antibodies of some HSV-infected human patients also reacted with BV gD. In contrast, only sera of HSV-1- and HSV-2-infected humans, but not sera from BV-infected macaques, reacted with HSV-1/2 gG. Collectively, these results suggest that both SA8 and HVP-2 allow for sensitive and comparable detection of BV-directed antibody responses in macaques and that the combination of BV gD and HSV-1/2 gG needs to be complemented by a least one additional viral glycoprotein for reliable discrimination between antibody responses against BV and HSV-1/2 in humans.
B 型疱疹病毒（BV）感染在成年亚洲猕猴中非常普遍，且在受感染动物中很少引发严重疾病。相比之下，人类感染 BV 若不进行治疗可诱发致命性脑炎。因此，开发用于特异性和灵敏检测抗 BV 抗体的诊断测试是一项重要任务。抗 BV 抗体与其他灵长类动物相关单纯疱疹病毒的交叉反应性，可能提供了一个无需使用高致病性 BV 就能获得灵敏检测系统的机会。此外，有人提出使用重组病毒糖蛋白可能能够高特异性地检测针对 BV 的抗体反应。然而，关于这两种 BV 诊断方法的数据都很有限。在此，我们报告，与感染 1 型和 2 型单纯疱疹病毒（HSV-1/2；感染人类）的细胞裂解物以及商用 HSV ELISA（Enzygnost Anti-HSV/IgG）相比，感染猿猴因子 8（SA8；感染非洲绿猴）和狒狒疱疹病毒 2（HVP-2；感染狒狒）的细胞能更灵敏地检测猕猴体内针对 BV 的抗体反应。此外，我们表明，来自感染 BV 的猕猴的血清中经常含有针对重组 BV 糖蛋白 gD（BV gD）的抗体，此前已有人提出将其作为区分 BV 和 HSV 诱导抗体的诊断靶点。然而，我们发现一些感染 HSV 的人类患者的抗体也与 BV gD 发生反应。相比之下，只有感染 HSV-1 和 HSV-2 的人类血清与 HSV-1/2 IgG 发生反应，而感染 BV 的猕猴血清则不反应。总体而言，这些结果表明，SA8 和 HVP-2 都能灵敏且可比地检测猕猴体内针对 BV 的抗体反应，并且为了可靠地区分人类针对 BV 和 HSV-1/2 的抗体反应，除了 BV gD 和 HSV-1/2 IgG 组合外，还需要至少一种额外的病毒糖蛋白。
