Colorado tick fever virus (CTFV) is an emerging Coltivirus belonging to the Reoviridae family and Spinareoviridae subfamily which can cause severe disease in humans. Several strains of CTFV have been previously described in the literature, including S6‐14‐03 (CTFV‐Ca), and the coltivirus‐type species, CTFV‐Florio. Following recent full genome sequencing, CTFV‐Ca is proposed to be a unique species within the Coltivirus genus rather than a serotype of CTFV‐Florio. CTFV‐Ca is closely related to human pathogenic coltiviruses, suggesting characterization is necessary to assess its pathogenic potential. We compared the ability of CTFV‐Florio and CTFV‐Ca to infect and proliferate within human dermal microvascular endothelial cells (HMEC‐1s) and detailed the potential immune responses during infection. Our results indicate that, like CTFV‐Florio, CTFV‐Ca is capable of infecting and proliferating within human endothelial cells (ECs). However, CTFV‐Ca is less efficient than CTFV‐Florio in our assays. Using RT‐qPCR gene arrays, we identified 41 genes that are significantly upregulated (> 2‐fold) upon infection including various proinflammatory cytokines and chemokines. Among the differentially upregulated genes, CTFV‐Florio typically induced a stronger response including on each occasion where significant differences were observed between the viruses. We also found both CTFV‐Florio and CTFV‐Ca capable of inducing proinflammatory responses at posttranslational levels as evidenced by significantly increased secretions of IFN‐β, IL‐6, IL‐8, and MCP‐1. Finally, we observed both increased EC permeability and death during CTFV‐Florio and CTFV‐Ca infection. These data describe for the first time a prospective antiviral response of human ECs to CTFV‐Ca infection and suggest that CTFV‐Ca can infect and stimulate potent antiviral and proinflammatory responses similar to the pathogenic Coltivirus ‐type species, CTFV‐Florio.
Burch et al. (Thu,) studied this question.