Bandavirus dabieense: A review of epidemiology, clinical characteristics, pathophysiology, treatment and prevention

Abstract

Bandavirus dabieense (commonly known as severe fever with thrombocytopenia syndrome virus, SFTSV) infection leads to severe fever with thrombocytopenia syndrome (SFTS), which is an emerging tick-borne natural focus disease discovered in middle-eastern China. SFTS is characterized by fever with thrombocytopenia, and patients' main clinical manifestations are leucopenia, elevated serum liver enzymes, and multiple organ failure. Ticks are considered as carriers of SFTSV transmission, and Haemaphysalis longicornalis is considered the main vector tick. SFTSV is disseminated through the migration or movement of tick-carrying migratory birds and other animal hosts. With changes in climate and environment, the habitat of ticks such as haemaphysalis longicornalis are continuously expanding, coupled with the diverse animal host species of the ticks. SFTS is evolving into a serious global public safety issue. In the absence of specific treatments and vaccines still being developed, monitoring and vector control are crucial for curbing the spread of SFTSV. Here, based on the existing literature, we reviewed the epidemiology, infection mechanism, clinical characteristics, diagnosis, prevention and clinical treatment of SFTSV to enhance the understanding of the SFTSV, with the aim of providing a theoretical basis guidance for the government and relevant institutions to prevent and control the further spread of SFTSV.

Keywords: Bandavirus dabieense; diagnosis; epidemiology; prevention; treatment.

Figure 1.

Genomic structure of SFTSV. SFTSV is an enveloped, segmentalized negative-stranded RNA virus, with spherical virions about 80 ~ 100 nm in diameter. The SFTSV genome consists of three RNA segments, large (L), medium (M), and small (S). The L segment encodes the RNA-dependent RNA polymerase (RdRp) and the M segment encodes the Gp, which can be cut and processed by cellular proteases into two subunits: glycoprotein N (Gn) and glycoprotein C (Gc) during translation. The S fragment belongs to the ambisense RNA family and has two opposite reading frames encoding two proteins from both directions, the 3’end reverse sequence encoding nuclear protein (NP) and the 5’ end sequence encoding non-structured (NSs) protein.

Figure 2.

Spread of SFTSV. (a), Transmission of SFTSV among ticks, animals and humans. SFTSV can be transmitted throughout the entire development cycle of Haemaphysalis longicornis, from larva, warts to adults, requiring a bloodsucking host change to form the tick-vertebrate-tick cycle. Humans are infected with SFTSV primarily through tick bites or through direct contact with the blood and/or body fluids of infected animals or patients (Created with BioRender.com). (b), the global distribution data Haemaphysalis longicornis detected between 1978 ~ 2023, the database comes from GBIF.Org (June 7, 2023) GBIFOC currence. Download at https://doi.org/10.15468/dl.Tvwagv, screening coordinate instrument uncertainty value <3. The size of the circle represents the abundance of Haemaphysalis longicornis. (c), Distribution of SFTS cases and positive animal samples in the Asian region. The green solid circle represents the distribution of SFTS cases, mainly concentrated in the southeastern coastal areas of China, japan, and South Korea. The blue hollow circle represents the animal samples that have detected SFTSV, including other ticks.

Figure 3.

SFTSV replication. ① SFTSV is attached to cells by Gp binding to host DC-SIGN, HS, NMMHC-IIA and other cytokines. ② it is further internalized through the endocytic pathway in a clathrin-dependent manner. ③ in the endosome stage, low pH triggers membrane fusion activity of Gc glycoproteins, allowing viral ribonucleoprotein complexes (vRnps) to be released into the cytoplasm. ④-⑧ vRNA in vRnps directs the synthesis of cRNA, which is assembled with newly synthesized RdRp and NP into complementary RNA (cRnps). Progeny vRnps are generated using cRnps as a template, and progeny vRnps can be used as a template to generate more vRnps. ⑨vrnps released into the cytoplasm migrate to the endoplasmic reticulum, where they direct the synthesis of viral proteins through transcription-coupled translation mechanisms. Viral nucleoproteins and RdRp enzymes are synthesized in the cytoplasm to form ribonucleoprotein (RNP) complexes. The viral glycoprotein GP is translated into the precursor protein Gn/Gc in the rough endoplasmic reticulum (ER). ⑩-⑪ Assembly of virus particles. Properly folded Gn/Gc heterodimers are transported to the golgi organ, where they bind to RNPs via the cytoplasmic tail of Gn during budding. ⑫-⑬ Vesicles containing the virus are transported to the cell membrane, where the virus particles are released through exocytosis (Created with BioRender.com).

Figure 4.

SFTSV infection and symptoms. (a), SFTSV is usually transmitted through the bite of a tick that carries the virus. Infection of skin resident cells, such as mast cell degranulation, resulted in damage to vascular endothelial cells. After the virus enters the bloodstream, platelets can carry and replicate SFTSV. SFTSV invades the secondary lymphoid organs closest to tick bite wounds, infecting cells such as B cells and macrophages, thereby achieving replication and transmission in the body (Created with BioRender.com). (b), Detection of infected cells in various organs. The number of cells infected in different organs varies. SFTSV-infected B-cell lineage lymphocytes are widely distributed in lymphatic and non-lymphoid organs, and occasionally these cells can be observed infiltrating the capillaries of the organ. The most infected cells were first detected in the bone marrow, spleen, lymph nodes, followed by the liver, adrenal glands, then the intestines, lungs, then the kidneys, and finally almost no infected cells were detected in the heart (created with BioRender.com).