Marburg Virus

Marburg virus, also known as green monkey virus, is named after the West German city of Marburg. The virus body is polymorphic, branching or coiled, and coiled into a U-shape, a "6" shape, or a ring. It is a deadly virus and the first filamentous virus discovered by humans, which can cause Marburg hemorrhagic fever. This virus shares the same lineage as Ebola virus and belongs to the family of filamentous viruses. It is also a common disease among humans and other primates, originating from Uganda and Kenya in Africa. Marburg virus is transmitted from animals to humans, but the source of the virus is not yet clear. Animals infected with viruses are important sources of infection, which can be transmitted through contact, injection, sexual contact (controversial), and other means. The main symptoms of the patient are high fever, diarrhea, vomiting, severe bleeding, etc. Usually, death occurs one week after the onset of the illness. The mortality rate of the disease is 25% to 100%. The inspection methods mainly include antibody testing and pathogen examination. Diagnosis requires comprehensive judgment based on medical history and clinical manifestations. There is currently no effective vaccine or specific therapy for this highly contagious and deadly disease.

Figure 1. MARV replication cycle. (Schmidt, Kristina Maria,et al, 2016)

Marburg Virus Genome and Targets

The MARV genome is a single-stranded, negative-sense RNA molecule, typically around 19 kb in length. It encodes seven structural proteins in the order 3′-NP–VP35–VP40–GP–VP30–VP24–L–5′.

Figure 2. Scheme of the Marburg virus (MARV) genome (top) and the minigenome (bottom) in negative-sense orientation. (Schmidt, Kristina Maria,et al, 2016)

• Nucleoprotein (NP): Encapsidates the viral RNA, essential for the synthesis of the viral genome and transcription.
• VP35 (Viral protein 35): A polymerase cofactor and a potent interferon (IFN) antagonist, crucial for suppressing the host immune response. This protein is a key therapeutic target for inhibiting viral replication and dampening immune evasion.
• VP40 (Viral protein 40): The major matrix protein that drives virion assembly and budding from the host cell. Targeting the VP40 domain responsible for oligomerization and membrane association can potentially block virus release.
• Glycoprotein (GP): A type I transmembrane glycoprotein found on the virion surface. It mediates receptor binding and host cell entry (a critical entry target). The GP is the primary antigen that triggers neutralizing antibody responses and is the focus of most vaccine efforts.

Biological Characteristics

The virus has moderate resistance to heat and cannot be completely inactivated after 30 minutes at 56 ℃, but its infectivity is lost after heating to 60 ℃ for 1 hour. The virus can be stored for a long time at -70 ℃, and is stable at 4 ℃ and room temperature (20 ℃). Its infectivity remains basically unchanged after 35 days of storage, but at 56 days, its titer decreases by half at 4 ℃ and by 1/10 at room temperature. A certain dose of ultraviolet and gamma ray irradiation can completely inactivate the virus. Viruses are sensitive to various chemicals and disinfectants. Acetic acid, ether, chloroform, and deoxycholic acid salts can completely destroy the infectivity of viruses. Formaldehyde, methanol, sodium hypochlorite, etc. can also completely inactivate viruses. Viruses are insensitive to actinomycin D and bromodeoxyuridine.

Pathogenesis

After entering the human body, Marburg virus first invades dendritic cells and macrophages, then is carried to regional lymph nodes, spreads within the lymphatic system, and infects the liver, spleen, and other tissues through blood circulation. Viral infection can cause direct damage to host cells, and in addition, the body's immune system can also damage cells. The pathogenesis of this disease mainly includes the following two aspects:

1. Direct damage to host cells caused by viral infection: The mechanism is that the virus binds to lectins on the cell surface, leading to cell necrosis through the toxic effects of viral proteins.
2. The interaction between viruses and the body's immune system leads to indirect damage to cells: the mechanism is that the virus spreads from the invasion site to various systems, thereby inhibiting the body's innate immune response, including the response of dendritic cells and macrophages to type 1 interferon Due to viral infection, dendritic cells partially inhibit the activation of T cells, thereby affecting humoral immune responses During the entire infection process, a large number of lymphocytes undergo apoptosis, leading to immune suppression Infected macrophages produce various mediators and cause severe lesions through various pathways, such as disseminated intravascular coagulation triggered by tissue factor expression on the cell surface; The release of cytokines and chemokines leads to vascular dysfunction, hypotension, and multiple organ failure.

Laboratory Tests

Anti-Marburg Virus Antibody

Marburg Virus Antigens