Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA.
Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, USA.
J Gen Virol. 2021 Sep;102(9). doi: 10.1099/jgv.0.001647.
Most flaviviruses are transmitted horizontally between vertebrate hosts by haematophagous arthropods. Others exhibit host ranges restricted to vertebrates or arthropods. Vertebrate-specific flaviviruses are commonly referred to as no-known-vector (NKV) flaviviruses and can be separated into bat- and rodent-associated NKV flaviviruses. Rio Bravo virus (RBV) is one of eight recognized bat-associated NKV (B-NKV) flaviviruses. Studies designed to identify the genetic determinants that condition the host range restriction of B-NKV flaviviruses have never been performed. To investigate whether the host range restriction occurs at the level of attachment or entry, chimeric flaviviruses were created by inserting the pre-membrane and envelope protein genes of RBV into the genetic backbones of yellow fever virus (YFV) and Zika virus (ZIKV), two mosquito-borne flaviviruses associated with human disease. The chimeric viruses infected both vertebrate and mosquito cells. In vertebrate cells, all viruses produced similar mean peak titres, but the chimeric viruses grew more slowly than their parental viruses during early infection. In mosquito cells, the chimeric virus of YFV and RBV grew more slowly than YFV at early post-inoculation time points, but reached a similar mean peak titre. In contrast, the chimeric virus of ZIKV and RBV produced a mean peak titre that was approximately 10-fold lower than ZIKV. The chimeric virus of YFV and RBV produced an intermediate plaque phenotype, while the chimeric virus of ZIKV and RBV produced smaller plaques than both parental viruses. To conclude, we provide evidence that the structural glycoproteins of RBV permit entry into both mosquito and vertebrate cells, indicating that the host range restriction of B-NKV flaviviruses is mediated by a post-attachment/entry event.
大多数黄病毒通过吸血节肢动物在脊椎动物宿主之间水平传播。其他病毒的宿主范围仅限于脊椎动物或节肢动物。脊椎动物特异性黄病毒通常被称为无已知媒介（NKV）黄病毒，可分为蝙蝠和啮齿动物相关的 NKV 黄病毒。里奥布拉沃病毒（RBV）是 8 种已识别的蝙蝠相关 NKV（B-NKV）黄病毒之一。尚未进行旨在确定条件限制 B-NKV 黄病毒宿主范围的遗传决定因素的研究。为了研究宿主范围限制是否发生在附着或进入水平，通过将 RBV 的前膜和包膜蛋白基因插入黄热病病毒（YFV）和寨卡病毒（ZIKV）的遗传骨架中，创建了嵌合黄病毒，这两种蚊媒黄病毒与人类疾病有关。嵌合病毒感染了脊椎动物和蚊子细胞。在脊椎动物细胞中，所有病毒产生的平均峰值滴度相似，但在早期感染期间，嵌合病毒的生长速度比其亲本病毒慢。在蚊子细胞中，嵌合的 YFV 和 RBV 病毒在早期接种后生长速度比 YFV 慢，但达到相似的平均峰值滴度。相比之下，嵌合的 ZIKV 和 RBV 病毒产生的平均峰值滴度比 ZIKV 低约 10 倍。嵌合的 YFV 和 RBV 病毒产生了中间菌斑表型，而嵌合的 ZIKV 和 RBV 病毒产生的菌斑比亲本病毒都小。总之，我们提供的证据表明，RBV 的结构糖蛋白允许进入蚊子和脊椎动物细胞，这表明 B-NKV 黄病毒的宿主范围限制是由附着/进入后的事件介导的。
