Dabie bandavirus

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Classification

Orthornavirae; Negarnaviricota; Ellioviricetes; Bunyavirales; Phenuiviridae; Bandavirus


Species

NCBI: [1]


Bandavirus dabieense

Description and Significance

The Dabie bandavirus, a tick-borne virus, was fist identified in China and is primarily transmitted through the bite of specific tick species that thrive in forested and rural areas. These ticks are well-adapted to humid environments, which support their lifecycle and population growth, making such regions hotspots for virus transmission (Kim & Park, 2023). The virus is primarily endemic to East Asia, including China, Korea, and Japan, but it poses a growing threat of global spread due to the migration of tick populations. The virus can infect a wide range of animals, which act as reservoirs and contribute to its persistence in the environment (Kim & Park, 2023). This zoonotic nature makes the virus difficult to control and enhances the risk of human exposure, particularly for individuals working in agriculture or other outdoor settings where tick encounters are frequent.

This virus is a significant public health concern because of the high mortality rates ranging between 10% to 30%, which highlights the virus’s lethality and the critical need for medical intervention in severe cases (Kim & Park, 2023). Although the virus is currently confined to East Asia, the expansion of tick habitats due to various changes to the environment increases the likelihood of its spread to new regions. Global health authorities are particularly concerned about the virus's potential to cause outbreaks, especially since there are no specific treatments or vaccines available. Treatment for Dabie bandavirus relies on supportive care and managing symptoms (Kim & Park, 2023).

Genome Structure

The bandavirus genus includes nine species, including the Dabie bandavirus which has a negative, segmented, single-stranded RNA genome (Kim et al., 2023). The genome of the bandavirus has five genes that encode for an RNA-dependent RNA polymerase (RdRp), a nucleocapsid protein (NP), a nonstructural protein (NSs), and two external glycoproteins (Gn and Gc) (Yu et al., 2011). There is a large (L), medium (M), and small (S) segment of the genome (Yu et al., 2011).

The L segment of the genome encodes for the RNA polymerase with 2084 residues of amino acids. It has an N-terminal endonuclease domain, polymerase core, and C-terminal cap-binding domain. Viral transcription is initiated in this segment when the RNA polymerase binds to the 5' cap of the host mRNA utilizing its cap-binding domain. This cuts the RNA and elongates it (Kim et al., 2023). Additionally, genome replication is initiated by the RNA polymerase, forming a viral RNA that is of full length using the complementary antigenomic RNA intermediate (Kim et al., 2023). Both the L and the M segments code using a negative sense coding strategy (Kim et al., 2023).

The M segment encodes a single open reading frame for the Gc and Gn glycoproteins precursors with 1073 amino acids (Yu et al., 2011). These proteins will bind to receptors in the cell in order for the virus to enter and penetrate the cell. When this happens, the Gc proteins are triggered to transport virions into endolysosomes with a pH ranging from 5.6-6 and will release the RNP complex composed with vRNA, RNA-dependent RNA, and N proteins (Kim et al., 2023).

The S segment has 1746 ambisense RNA nucleotides which encode for the NP and NSs proteins. There is a 54 nucleotide intergenic region between these, and they are oriented opposite of each other (Brennan et al., 2017). The N mRNA is transcribed from the viral sense, while NSs is from the antisense RNA intermediate (Kim et al., 2023). When the N protein associates with the RdRp, it will interact with the viral RNA and function as the RNA synthesis machinery. Translated Gn and Gc proteins are assembled by this RNP complex into the Golgi apparatus from which the infected virions will exit (Kim et al., 2023).

Schematic diagram of Dabie Bandavirus tructure. Image credit: Zhou & Yo, 2021

Cell Structure, Metabolism and Life Cycle

Dabie Bandavirus has a simple structure consisting only of nucleic acids encased in a protein coat and a lipid envelope. It is spherically shaped with a diameter of approximately 90-100nm (Liu et al., 2023). Its envelope is derived from the cell membrane of its host during the budding process, and it is a bilayer that holds the virus's glycoproteins that protrude from the surface. This envelope also protects the virus's components and is crucial for the virus's ability to infect a new host (Liu et al., 2023).

Dabie Bandavirus, like all other viruses, does not have the ability to generate energy on its own and, therefore, must utilize its host's metabolic resources. Dabie Bandavirus uses nonstructural proteins to facilitate energy acquisition and replication. These proteins interact with actin, an important component of the cytoskeleton in eukaryotic cells, which allows the virus to take over the host's machinery for its benefit (Liu et al., 2022).

Ecology and Pathogenesis

The Dabie Bandavirus is parasitic and is transmitted through tick bites, mainly the Asian longhorned tick. It can also spread through direct contact with the bodily fluids of infected people (Liu et al., 2022). Severe Fever with Thrombocytopenia Syndrome (SFTS), caused by Dabie Bandavirus is mainly spread in East Asian countries and was first identified in China (Kim et al., 2023). In addition to humans, the virus can infect various animals, including rats, livestock, and pets, which can act as reservoirs (Liu et al., 2022).

The symptoms of Dabie Bandavirus and SFTS are high fever, thrombocytopenia (low platelet count), leukopenia (low white blood cell count), and elevated liver enzymes. Severe cases can lead to hemorrhagic fever and multi-organ failure. The fatality rate varies but can be as high as 30% in severe cases, particularly among older adults (Liu et al., 2022). The virus uses its nonstructural proteins to control the host and help itself spread (Liu et al., 2022).

References

Brennan, B., Rezelj, V.V., & Elliott, R.M. 2017. Mapping of Transcription Termination within the S Segment of SFTS Phlebovirus Facilitated Generation of NSs Deletant Viruses. Journal of Virology. 91(16). https://journals.asm.org/doi/10.1128/jvi.00743-17 [Accessed 10 November 2024]

Kim, E.H., & Park, S.J. 2023. Emerging Tick-Borne Dabie bandavirus: Virology, Epidemiology, and Prevention. Microorganisms. 11(9). https://pmc.ncbi.nlm.nih.gov/articles/PMC10536723/ [Accessed 10 November 2024]

Liu, B., Zhu, J., He, T., & Zhang, Z. 2023. Genetic variants of Dabie bandavirus: classification and biological/clinical implications. Virology Journal. 20(68). https://doi.org/10.1186/s12985-023-02033-y [Accessed 30 November]

Liu, H., Liu, S., Liu, Z., Gao, X., Xu, L., Huang, M., Su, Y., Wang, Z., & Wang, T. 2022. Dabie bandavirus Nonstructural Protein Interacts with Actin to Induce F-Actin Rearrangement and Inhibit Viral Adsorption and Entry. Journal of Virology. 96(14). https://doi.org/10.1128/jvi.00788-22 [Accessed 30 November 2024]

Prasad, N. 2024. Breaking Medical News! Human-To-Human Transmission of Dabie Bandavirus That Causes SFTS Infections Confirmed in Japan. Thailand Medical News. https://www.thailandmedical.news/news/breaking-medical-news-human-to-human-transmission-of-dabie-bandavirus-that-causes-sfts-infections-confirmed-in-japan [Accessed 10 December 2024]

Yu, X.J., Liang, M.F., Zhang, S.Y., Liu, Y., Li, J.D., Sun, Y.L., Zhang, L. & Li, D.X. 2011. Fever with Thrombocytopenia Associated with a Novel Bunyavirus in China. The New England Journal of Medicine. 364(16). https://www.nejm.org/doi/full/10.1056/NEJMoa1010095 [Accessed 10 November 2024]

Zhou, C., & Yo, X. 2021. Unraveling the Underlying Interaction Mechanism Between Dabie bandavirus and Innate Immune Response. Frontiers Immunology. 12. https://doi.org/10.3389/fimmu.2021.676861 [Accessed 10 December 2024]

Author

Page authored by Molly McMorrow, Gabriella Clark, Jayden Sturm, & Janey Metts, students of Prof. Bradley Tolar at UNC Wilmington.