Global Health Update: The Rising Concern of the Marburg Virus Disease

Posted on 2024-10-14

In late September, the Republic of Rwanda reported an outbreak of Marburg Virus Disease (MVD), prompting global health authorities to be on alert (1). As of the 6th of October 2024, Rwanda has reported a total of 49 confirmed cases of the disease and 12 subsequent deaths (2). 

First recognised in 1967, the Marburg Virus (MARV) has sporadically caused infections and outbreaks (1). In 2005, the largest outbreak to date occurred in Angola, leading to confirmed 374 cases, and 329 deaths. Most MVD outbreaks have happened in Sub-Saharan Africa (3). However, travellers to endemic regions and laboratory personnel have also been previously infected (4). 


Curiosity
MVD is named after the German city where scientists became ill with the disease's first known cases in 1967 while handling monkeys imported from Uganda (4).
MARV causes MVD, a disease with a case fatality ratio of up to 88%. Marburg and Ebola viruses are both members of the Filoviridae (filovirus) family, characterised by being filamentous, enveloped and non-segmented, single-stranded negative-sense RNA viruses (1).

Filoviruses are known to cause severe haemorrhagic fever in humans and non-human primates. Infectious MARV has been isolated in Egyptian fruit bats in Uganda, indicating that this species is also susceptible to infection by the virus and may serve as the natural reservoir of the virus (5). Transmission of MARV can occur between direct in-species contamination, through sexual transmission or biting. Inter-species transmission can be due to direct contact with reservoir hosts or consumption of contaminated fruit (6). 

Pathogenesis of MARV

MARV pathogenesis begins with entry into host cells. The virus primarily targets cells of the mononuclear phagocytic system, which includes macrophages, dendritic and endothelial cells, among others (7).  In particular, the virus' glycoprotein (GP) plays a crucial role in viral attachment and entry. The GP interacts with specific host receptors (e.g., DC-SIGN, TIM-1), facilitating viral internalisation through receptor-mediator endocytosis. Once inside the cell, the virus undergoes a pH-dependent fusion process, releasing viral RNA into the cytoplasm (8).

Following viral entry, replication occurs in the cytoplasm. The viral RNA previously released will be the template for transcription and replication and will encode several key proteins, such as nucleoproteins, and viral proteins (VP) 35, VP40 and VP30 (9). These proteins will coordinate the synthesis of viral DNA and the assembly of new viral particles. In particular, the viral matrix protein, VP40, plays a crucial role in forming viral filaments, containing viral nucleocapsids with the RNA genome encapsidated by nucleoproteins, and budding of the plasma membrane. Once budding is complete, mature virions are released from infected cells, leading to systemic dissemination and infection of various organs (10). 

MARV employs various mechanisms to counteract host antiviral responses, such as suppression of interferon production and interference with cellular signalling pathways involved in immune activation (11). Viral infection triggers a dysregulated host immune response, which contributes to the pathogenesis of the disease. MARV can directly induce cell death, leading to tissue damage, and the release of pro-inflammatory mediators (12).

MARV Molecular Targets

  • Glycoprotein (GP)

The viral GP facilitates viral attachment and fusion with the host cell membrane, allowing the virus to enter and initiate infection. Targeting the GP has been a focus of therapeutic development, aiming to inhibit viral entry and prevent infection (8). Abbexa offers a GP antibody, which can be an essential tool in aiding the development of therapeutic strategies. 

  • VP40

As previously mentioned, VP40, as a viral matrix protein, is essential for assembling and budding new viral particles. Therefore, disrupting the interactions between these proteins and other cellular proteins involved in viral assembly can impair viral particle formation and release (9). Abbexa carries a VP40 antibody in its portfolio, which could be a crucial tool for facilitating the research into key viral life cycle mechanisms. 


References

  1. Marburg virus disease [Internet]. [cited 2024 Oct 10]. 
  2. Fact Sheet: HHS Actions to Support Response to Marburg Outbreak in Rwanda | HHS.gov [Internet]. [cited 2024 Oct 10].
  3. Marburg virus disease: origins, reservoirs, transmission and guidelines - GOV.UK [Internet]. [cited 2024 Oct 10].
  4. History of Marburg Outbreaks | Marburg | CDC [Internet]. [cited 2024 Oct 10]. 
  5. Takada A. Filovirus tropism: Cellular molecules for viral entry. Front Microbiol [Internet]. 2012 Feb 6 [cited 2024 Oct 10];3(FEB):21403.
  6. Abir MH, Rahman T, Das A, Etu SN, Nafiz IH, Rakib A, et al. Pathogenicity and virulence of Marburg virus. Virulence [Internet]. 2022 [cited 2024 Oct 10];13(1):609. 
  7. Sharma G, Sharma AR, Kim JC. Recent Advancements in the Therapeutic Development for Marburg Virus: Updates on Clinical Trials. Curr Infect Dis Rep [Internet]. 2024 Feb 1 [cited 2024 Oct 10];26(2):57–67. 
  8. Kajihara M, Marzi A, Nakayama E, Noda T, Kuroda M, Manzoor R, et al. Inhibition of Marburg Virus Budding by Nonneutralizing Antibodies to the Envelope Glycoprotein. J Virol [Internet]. 2012 Dec 15 [cited 2024 Oct 10];86(24):13467–74.  
  9. Dolnik O, Becker S. Assembly and transport of filovirus nucleocapsids. PLoS Pathog [Internet]. 2022 Jul 1 [cited 2024 Oct 10];18(7):e1010616. 
  10. Madara JJ, Han Z, Ruthel G, Freedman BD, Harty RN. The Multifunctional Ebola Virus VP40 Matrix Protein is a Promising Therapeutic Target. Future Virol [Internet]. 2015 May 1 [cited 2024 Oct 10];10(5):537–46. 
  11. Edwards MR, Liu G, Mire CE, Sureshchandra S, Luthra P, Yen B, et al. Differential Regulation of Interferon Responses by Ebola and Marburg Virus VP35 Proteins. Cell Rep [Internet]. 2016 Feb 23 [cited 2024 Oct 10];14(7):1632–40.
  12. Shifflett K, Marzi A. Marburg virus pathogenesis - Differences and similarities in humans and animal models. Virol J [Internet]. 2019 Dec 30 [cited 2024 Oct 10];16(1):1–12.