Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 300 W, Drake Rd, Fort Collins, Colorado 80523, USA.
Vet Res. 2011 Feb 7;42(1):23. doi: 10.1186/1297-9716-42-23.
Equine herpesvirus-1 (EHV-1) infection remains a significant problem despite the widespread use of vaccines. The inability to generate a protective immune response to EHV-1 vaccination or infection is thought to be due to immunomodulatory properties of the virus, and the ORF1 and ORF2 gene products have been hypothesized as potential candidates with immunoregulatory properties. A pony infection study was performed to define immune responses to EHV-1, and to determine if an EHV-1 ORF1/2 deletion mutant (ΔORF1/2) would have different disease and immunoregulatory effects compared to wild type EHV-1 (WT). Infection with either virus led to cytokine responses that coincided with the course of clinical disease, particularly the biphasic pyrexia, which correlates with respiratory disease and viremia, respectively. Similarly, both viruses caused suppression of proliferative T-cell responses on day 7 post infection (pi). The ΔORF1/ORF2 virus caused significantly shorter primary pyrexia and significantly reduced nasal shedding, and an attenuated decrease in PBMC IL-8 as well as increased Tbet responses compared to WT-infected ponies. In conclusion, our findings are (i) that infection of ponies with EHV-1 leads to modulation of immune responses, which are correlated with disease pathogenesis, and (ii) that the ORF1/2 genes are of importance for disease outcome and modulation of cytokine responses.
马疱疹病毒 1 型（EHV-1）感染仍然是一个重大问题，尽管广泛使用了疫苗。人们认为，无法对 EHV-1 疫苗接种或感染产生保护性免疫反应，是由于病毒的免疫调节特性，并且 ORF1 和 ORF2 基因产物被假设为具有免疫调节特性的潜在候选物。进行了一项小马驹感染研究，以确定对 EHV-1 的免疫反应，并确定 EHV-1 ORF1/2 缺失突变体（ΔORF1/2）与野生型 EHV-1（WT）相比是否具有不同的疾病和免疫调节作用。感染任何一种病毒都会导致细胞因子反应，与临床疾病的进程相吻合，特别是双峰发热，分别与呼吸道疾病和病毒血症相关。同样，两种病毒都会导致感染后第 7 天（pi）增殖性 T 细胞反应受到抑制。与 WT 感染的小马驹相比，ΔORF1/ORF2 病毒引起的原发性发热明显缩短，鼻分泌物明显减少，以及 PBMC IL-8 减少和 Tbet 反应增加。总之，我们的发现是：（i）EHV-1 感染小马驹会导致免疫反应的调节，这与疾病发病机制相关；（ii）ORF1/2 基因对疾病结局和细胞因子反应的调节很重要。
