Severe fever with thrombocytopenia syndrome virus: emerging novel phlebovirus and their control strategy

Abstract

An emerging infectious disease first identified in central China in 2009, severe fever with thrombocytopenia syndrome (SFTS) was found to be caused by a novel phlebovirus. Since SFTSV was first identified, epidemics have occurred in several East Asian countries. With the escalating incidence of SFTS and the rapid, worldwide spread of SFTSV vector, it is clear this virus has pandemic potential and presents an impending global public health threat. In this review, we concisely summarize the latest findings regarding SFTSV, including vector and virus transmission, genotype diversity and epidemiology, probable pathogenic mechanism, and clinical presentation of human SFTS. Ticks most likely transmit SFTSV to animals including humans; however, human-to-human transmission has been reported. The majority of arbovirus transmission cycle includes vertebrate hosts, and potential reservoirs include a variety of both domestic and wild animals. Reports of the seroprevalence of SFTSV in both wild and domestic animals raises the probability that domestic animals act as amplifying hosts for the virus. Major clinical manifestation of human SFTS infection is high fever, thrombocytopenia, leukocytopenia, gastrointestinal symptoms, and a high case-fatality rate. Several animal models were developed to further understand the pathogenesis of the virus and aid in the discovery of therapeutics and preventive measures.

Fig. 1. SFTSV genetic reassortment within a host.

a Domestic and wild animals are readily infected with SFTSV from virus-carrying ticks during blood-feeding. Individual ticks may harbor different genotypes of SFTSV, thus causing superinfection to the vertebrate host. b Due to the segmented genome of the virus, the exchange of segments may happen between co-infecting SFTSV genotypes within the host cell during virus replication, generating a novel viral strain. c During the viremic period of the vertebrate host, ticks may acquire the virus during blood-feeding, further continuing the virus cycle and transferring the virus as it switches to a new vertebrate host (Created with BioRender.com).

Fig. 2. Probable mechanism of SFTSV pathogenesis.

a SFTSV transmission to humans commonly occurs from virus-carrying-tick-bite. b The SFTSV then invades the lymph node nearest to the tick-bite wound, targeting immune cells such as B-cells, impairing host immune response from invading pathogen. c After further replication, the virus goes to the systemic circulation, in response to viremia, other immune cells are over-stimulated causing cytokine storm and severe inflammatory response syndrome (SIRS). d Thrombocytopenia is a hallmark of SFTSV infection; hence, several mechanisms may be attributed to the decrease of platelet count, such as, increase consumption of peripheral platelets from virus-induced activation of the coagulation pathway, which may be related to the occurrence of disseminated intravascular coagulation or due to endothelial damage from severe systemic inflammation, and by clearance of SFTSV-bound-platelet by splenic macrophages. e Disseminated intravascular coagulation and endothelial damage caused by cytokine storm lead to multi-organ dysfunction, reflected by the elevation of liver, kidney, and heart serum markers (Created with BioRender.com).