Infection Route Impacts the Pathogenesis of Severe Fever with Thrombocytopenia Syndrome Virus in Ferrets

Abstract

The threat of severe fever with thrombocytopenia syndrome (SFTS) to public health has been increasing due to the rapid spread of the ticks that carry the causative viral agent. The SFTS virus (SFTSV) was first identified in China and subsequently detected in neighboring countries, including South Korea, Japan, and Vietnam. In addition to the tick-mediated infection, human-to-human transmission has been recently reported with a high mortality rate; however, differential study of the pathogen has been limited by the route of infection. In this study, we investigated the pathogenic potential of SFTSV based on the infection route in aged ferrets, which show clinical signs similar to that of human infections. Ferrets inoculated with SFTSV via the intramuscular and subcutaneous routes show clinical signs comparable to those of severe human infections, with a mortality rate of 100%. Contrastingly, intravascularly infected ferrets exhibit a comparatively lower mortality rate of 25%, although their early clinical signs are similar to those observed following infection via the other routes. These results indicate that the infection route could influence the onset of SFTS symptoms and the pathogenicity of SFTSV. Thus, infection route should be considered in future studies on the pathogenesis of SFTSV infection.

Heartland Virus: An Evolving Story of an Emerging Zoonotic and Vector-Borne Disease

“…In contrast to the sparsity of information available on HRTV pathogenesis, much more is known about the pathogenesis of SFTSV in a range of wild-type and immunodeficient model systems. Though many of the species investigated were of limited value for better understanding SFTSV infections in humans, lacking some key features of the disease process (summarized in a recent review by Sun et al [34]), studies in ferrets [38], cats [39], and non-human primates [40][41][42] have found that these species may share some key features of disease in humans. Studies in rhesus macaques, for example, revealed that they have patterns of viremia, tissue distribution, and pathology which mirror those observed in human SFTSV infections [40,42].…”