Louisiana Animal Disease Diagnostic Laboratory, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
Viruses. 2024 Sep 21;16(9):1497. doi: 10.3390/v16091497.
Bovine herpesvirus type 1 (BoHV-1) establishes lifelong latency in trigeminal ganglionic (TG) neurons following intranasal and ocular infection in cattle. Periodically, the latent virus reactivates in the TG due to stress and is transported anterogradely to nerve endings in the nasal epithelium, where the virus replicates and sheds. Consequently, BoHV-1 is transmitted to susceptible animals and maintained in the cattle population. Modified live BoHV-1 vaccine strains (BoHV-1 MLV) also have a similar latency reactivation. Therefore, they circulate and are maintained in cattle herds. Additionally, they can regain virulence and cause vaccine outbreaks because they mutate and recombine with other circulating field wild-type (wt) strains. Recently, we constructed a BoHV-1 quadruple mutant virus (BoHV-1qmv) that lacks immune evasive properties due to UL49.5 and glycoprotein G (gG) deletions. In addition, it also lacks the gE cytoplasmic tail (gE CT) and Us9 gene sequences designed to make it safe, increase its vaccine efficacy against BoHV-1, and restrict its anterograde neuronal transport noted above. Further, we engineered the BoHV-1qmv-vector to serve as a subunit vaccine against the Rift Valley fever virus (BoHV-1qmv Sub-RVFV) (doi: 10.3390/v15112183). In this study, we determined the latency reactivation and nasal virus shedding properties of BoHV-1qmv (vector) and BoHV-1qmv-vectored subunit RVFV (BoHV-1qmv sub-RVFV) vaccine virus in calves in comparison to the BoHV-1 wild-type (wt) following intranasal inoculation. The real-time PCR results showed that BoHV-1 wt- but not the BoHV-1qmv vector- and BoHV-1qmv Sub-RVFV-inoculated calves shed virus in the nose following dexamethasone-induced latency reactivation; however, like the BoHV-1 wt, both the BoHV-1qmv vector and BoHV-1qmv Sub-RVFV viruses established latency, were reactivated, and replicated in the TG neurons. These results are consistent with the anterograde neurotransport function of the gE CT and Us9 sequences, which are deleted in the BoHV-1qmv and BoHV-1qmv Sub-RVFV.
牛疱疹病毒 1 型（BoHV-1）在牛通过鼻腔和眼部感染后，在三叉神经节（TG）神经元中建立终身潜伏。由于应激，潜伏病毒会周期性地重新激活，并沿轴突向前运输到鼻上皮的神经末梢，在那里病毒复制和脱落。因此，BoHV-1 传播给易感动物，并在牛群中维持。经过改良的活 BoHV-1 疫苗株（BoHV-1 MLV）也具有类似的潜伏再激活。因此，它们在牛群中循环并得到维持。此外，它们可能会恢复毒力并引发疫苗爆发，因为它们会发生突变并与其他循环的野生型（wt）株重组。最近，我们构建了一种 BoHV-1 四重突变病毒（BoHV-1qmv），由于 UL49.5 和糖蛋白 G（gG）缺失，它缺乏免疫逃避特性。此外，它还缺失了 gE 细胞质尾巴（gE CT）和 Us9 基因序列，这些序列的设计目的是使其安全，提高其针对 BoHV-1 的疫苗效力，并限制其上述的前向神经元运输。此外，我们设计了 BoHV-1qmv 载体作为裂谷热病毒（BoHV-1qmv Sub-RVFV）的亚单位疫苗（doi：10.3390/v15112183）。在这项研究中，我们确定了 BoHV-1qmv（载体）和 BoHV-1qmv 载体亚单位 RVFV（BoHV-1qmv sub-RVFV）疫苗病毒在牛中的潜伏再激活和鼻腔病毒脱落特性，与鼻腔接种后的 BoHV-1 野生型（wt）进行了比较。实时 PCR 结果表明，只有 BoHV-1 wt 而不是 BoHV-1qmv 载体和 BoHV-1qmv Sub-RVFV 接种的小牛在 dexamethasone 诱导的潜伏再激活后会从鼻子中排出病毒；然而，与 BoHV-1 wt 一样，BoHV-1qmv 载体和 BoHV-1qmv Sub-RVFV 病毒都建立了潜伏、被重新激活，并在 TG 神经元中复制。这些结果与 gE CT 和 Us9 序列的顺行神经转运功能一致，这些序列在 BoHV-1qmv 和 BoHV-1qmv Sub-RVFV 中被缺失。
