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  3. Orthoebolavirus
About Orthoebolavirus

The genus Orthoebolavirus (formerly Ebolavirus) belongs to the family Filoviridae, order Mononegavirales, and its members were first discovered in 1976 during two independent outbreaks that occurred simultaneously in Yambuku, Zaire (now the Democratic Republic of the Congo) and Nzara, Sudan. Members of the genus Orthoebolavirus are filamentous, enveloped viruses with pleomorphic morphology, predominantly appearing as long filaments approximately 800–1,000 nm in length (though they may also form branched, "U"-shaped, "6"-shaped, and other aberrant morphologies), with a uniform diameter of approximately 80 nm. The genome is a non-segmented, single-stranded, negative-sense RNA approximately 18.8–19.1 kb in length, containing seven genes encoding eight proteins: nucleoprotein (NP), virion protein 35 (VP35, interferon antagonist/cofactor), virion protein 40 (VP40, matrix protein), glycoprotein (GP), virion protein 30 (VP30, transcription cofactor), virion protein 24 (VP24, secondary matrix protein/immune modulator), and RNA-dependent RNA polymerase (L). In addition, the GP gene produces a soluble glycoprotein (sGP) and a small soluble glycoprotein (ssGP) through transcriptional editing (insertion of an extra adenosine at the editing site), with sGP being abundantly secreted during early infection and functioning as a neutralizing antibody decoy and immunomodulator.

Based on whole-genome genetic characteristics and serological differences, the genus Orthoebolavirus comprises six species: Zaire orthoebolavirus (EBOV/ZEBOV), Sudan orthoebolavirus (SUDV), Bundibugyo orthoebolavirus (BDBV), Taï Forest orthoebolavirus (TAFV), Reston orthoebolavirus (RESTV), and Bombali orthoebolavirus (BOMV). Among these, EBOV is the most pathogenic, with historical case fatality rates of 25–90%; SUDV has a case fatality rate of approximately 40–50%, and an rVSV-SUDV vaccine has been approved (though not yet widely deployed); BDBV has a case fatality rate of approximately 30–50%; TAFV has only a single reported human infection with mild symptoms; RESTV can infect humans but no disease has been reported to date; and BOMV has been detected only in bats with no evidence of human infection. Notably, the geographic distributions of different species are distinct: EBOV is primarily found in the Congo Basin and West Africa, SUDV mainly in East Africa (Sudan and Uganda), BDBV was identified in the border region between the Democratic Republic of the Congo and Uganda, TAFV has been detected only in Côte d'Ivoire, RESTV has been found in pigs and non-human primates in the Philippines and China, and BOMV has been identified in bats in Sierra Leone and Guinea. Significant genetic diversity also exists among outbreak strains within the same species; during the 2013–2016 West Africa epidemic, EBOV evolved at a rate of approximately 1.2 × 10⁻³ substitutions per site per replication, and adaptive mutations associated with enhanced human cell infectivity, such as GP-A82V, emerged. The Makona lineage generated during this epidemic subsequently reappeared during the 2018–2020 eastern Democratic Republic of the Congo outbreak, suggesting the possibility of viral persistence with reactivation or sexual transmission.

Members of the genus Orthoebolavirus are primarily distributed in sub-Saharan Africa (with the exception of RESTV), with outbreaks occurring in an episodic pattern without a clear seasonal trend. These viruses are transmitted through direct contact with blood, body fluids, or tissues of infected individuals, and can also be spread via aerosols among non-human primates. The incubation period ranges from 2 to 21 days (median 5–7 days). The viruses initially infect innate immune cells such as dendritic cells and macrophages, then disseminate through the lymphatic system and bloodstream to target organs including the liver, spleen, and adrenal glands, leading to massive lymphocyte apoptosis, cytokine storm, and coagulopathy. Clinical manifestations progress from non-specific symptoms such as fever, fatigue, and myalgia to vomiting, diarrhea, rash, renal and hepatic impairment, and severe symptoms including internal and external hemorrhage. Critically ill patients often succumb to hypovolemic shock and multiple organ failure. The rVSV-ZEBOV vaccine (Ervebo®) has been approved for EBOV prevention, and the Ad26.ZEBOV/MVA-BEBOV two-dose regimen (Zabdeno/Mvabea®) is available for immunization; therapeutically, Inmazeb® (a three-monoclonal antibody combination) and Ebanga® (ansuvimab, a single monoclonal antibody) have been approved for the treatment of EBOV infection, though supportive care—including fluid resuscitation, electrolyte balance, and organ function support—remains the foundation of clinical management. Vaccines and monoclonal antibody therapies targeting SUDV are currently in clinical trials.

 

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References

[1] BOWEN E T, LLOYD G, HARRIS W J, et al. Viral haemorrhagic fever in southern Sudan and northern Zaire. Preliminary studies on the aetiological agent [J]. The Lancet, 1977, 309(8011): 571-3.

[2] KUHN J H, AMARASINGHE G K, BAH E C, et al. ICTV virus taxonomy profile: Filoviridae [J]. Journal of General Virology, 2019, 100(6): 912-4.

[3] BAIZE S, PANNETIER D, OESTEREICH L, et al. Emergence of Zaire Ebola virus disease in Guinea [J]. The New England Journal of Medicine, 2014, 371(15): 1418-26.

[4] TOWNER J S, SEMLANDT L, ABEDI A A, et al. Isolation of genetically distinct Marburg virus from a newly identified natural host, the African fruit bat Rousettus aegyptiacus—implications for filovirus ecology and evolution [J]. PLoS Pathogens, 2009, 5(11): e1000629. 

[5] VOLCHKOV V E, BECKER S, KLENK H D, et al. GP mRNA of Ebola virus is edited by the Ebola virus polymerase and not by a cellular enzyme [J]. Journal of Virology, 1995, 69(6): 3756-8.

[6] HENAO-RESTREPO A M, CAMACHO A, LONGINI I M, et al. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!) [J]. The Lancet, 2017, 389(10068): 505-18.

[7] FELDMANN H, GEISBERT T W. Ebola haemorrhagic fever [J]. The Lancet, 2011, 377(9768): 849-62.

[8] GIRE S K, GOBA A, ANDERSEN K G, et al. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak [J]. Science, 2014, 345(6202): 1369-72.

[9] MULANGU S, DODD L E, DAVEY R T Jr, et al. A randomized, controlled trial of Ebola virus disease therapeutics [J]. The New England Journal of Medicine, 2019, 381(24): 2293-303.

[10] GOLDSTEIN T, ANTHONY S J, GBAKIMA A, et al. The discovery of Bombali virus adds further support for bats as hosts of ebolaviruses [J]. Nature Microbiology, 2018, 3(10): 1084-9.

 

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