Whitley Richard, Baines Joel
Department of Pediatrics, Microbiology, and Medicine, University of Alabama at Birmingham Children's Hospital, Birmingham, AL, 35233, USA.
Department of Pathobiology, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70803, USA.
F1000Res. 2018 Oct 31;7. doi: 10.12688/f1000research.16157.1. eCollection 2018.
Infection with herpes simplex virus (HSV) types 1 and 2 is ubiquitous in the human population. Most commonly, virus replication is limited to the epithelia and establishes latency in enervating sensory neurons, reactivating periodically to produce localized recurrent lesions. However, these viruses can also cause severe disease such as recurrent keratitis leading potentially to blindness, as well as encephalitis, and systemic disease in neonates and immunocompromised patients. Although antiviral therapy has allowed continual and substantial improvement in the management of both primary and recurrent infections, resistance to currently available drugs and long-term toxicity pose a current and future threat that should be addressed through the development of new antiviral compounds directed against new targets. The development of several promising HSV vaccines has been terminated recently because of modest or controversial therapeutic effects in humans. Nevertheless, several exciting vaccine candidates remain in the pipeline and are effective in animal models; these must also be tested in humans for sufficient therapeutic effects to warrant continued development. Approaches using compounds that modulate the chromatin state of the viral genome to suppress infection and reactivation or induce enhanced antiviral immunity have potential. In addition, technologies such as CRISPR/Cas9 have the potential to edit latent viral DNA in sensory neurons, potentially curing the neuron and patient of latent infection. It is hoped that development on all three fronts-antivirals, vaccines, and gene editing-will lead to substantially less HSV morbidity in the future.
单纯疱疹病毒1型和2型感染在人群中普遍存在。最常见的情况是，病毒复制局限于上皮细胞，并在支配性感觉神经元中建立潜伏状态，周期性重新激活以产生局部复发性病变。然而，这些病毒也可引起严重疾病，如复发性角膜炎，可能导致失明，以及脑炎，还有新生儿和免疫功能低下患者的全身性疾病。尽管抗病毒治疗已使原发性和复发性感染的管理持续取得实质性改善，但对现有药物的耐药性和长期毒性构成了当前和未来的威胁，应通过开发针对新靶点的新型抗病毒化合物来应对。由于在人体中的治疗效果一般或存在争议，最近几种有前景的单纯疱疹病毒疫苗的研发已终止。尽管如此，仍有几种令人兴奋的候选疫苗正在研发中，并且在动物模型中有效；这些疫苗也必须在人体中进行测试，以获得足够的治疗效果，从而保证继续研发。使用能够调节病毒基因组染色质状态以抑制感染和重新激活或诱导增强抗病毒免疫力的化合物的方法具有潜力。此外，CRISPR/Cas9等技术有潜力编辑感觉神经元中的潜伏病毒DNA，有可能治愈神经元和患者的潜伏感染。希望抗病毒药物、疫苗和基因编辑这三个方面的发展将在未来大幅降低单纯疱疹病毒的发病率。
