Dugbe virus was first isolated in Nigeria in 1964 from Amblyomma variegatum ticks. Ticks primarily transmit it and are commonly found in arid regions of Africa.  

It is closely related antigenically and genetically to Crimean-Congo hemorrhagic fever (CCHF), another tickborne virus that can cause severe human disease. DUGV is a low health hazard compared to the CCHF virus, as it is generally associated with mild or asymptomatic human infections. 

Handling of infected carcasses, notably in agricultural or veterinary settings where contact with infected animals may occur. Additionally, nosocomial transmission, which refers to the transmission of the virus within healthcare settings, is also a potential risk. 

Dugbe virus (DUGV) has been reported to circulate among cattle and various tick species, including Rhipicephalus (Boophilus) and Amblyomma ticks, in Kwara State of Nigeria. According to monitoring and study, DUGV has been identified in 35 (0.8%) of the 4,643 ticks examined. It has been detected in more than 13 African nations: Nigeria, Sudan, Cameroon, Ethiopia, Central African Republic, Uganda, Chad, Egypt, Kenya, Senegal, South Africa, Ghana, and Guinea. 

The virus has been frequently isolated from ticks that infest market livestock, indicating its presence in agricultural and rural environments. Due to its endemic nature, the Dugbe virus poses a continuous risk of infection to humans and animals in these regions, emphasizing the importance of tick control measures and surveillance programs to prevent its spread and minimize its impact on public health and agriculture. 

Kingdom: Virus 

Phylum: Negarnaviricota 

Class: Ellioviricetes 

Order: Bunyavirales 

Family: Bunyaviridae 

Genus: Nairovirus 

Species: Dugbe virus 

• Dugbe virus (DUGV) is characterized by a spherical particle with a diameter of approximately 90 nm. It is enveloped by a 5 nm thick membrane surrounding the viral core. 

• It has a tripartite genome consisting of single-stranded, negative-sense RNA segments. The three RNA segments are designated as L, M, and S segments. The L segment encodes for the RNA-dependent RNA polymerase, The M segment for the viral glycoproteins Gn and Gc, and the S segment for the nucleocapsid protein (N). 

• DUGV has 5-7 nm long projections or “spikes” covering the virus’s surface. These spikes are contributed to its infectivity. The spikes are arranged in a regular pattern and form hollow cylindrical morphological units with a diameter of about 5 nm. 

The dugbe virus is an associate of the Nairovirus genus & the Bunyaviridae family. It is closely linked to the viruses that cause Nairobi sheep disease (NSDV) and Crimea-Congo hemorrhagic fever (CCHFV). Ticks spread it, causing a moderate febrile sickness in humans and cattle. Antigenic variation can arise within and between inter-species or strains.  

The antigenic types of the Dugbe virus are not well characterized; however, recent research suggests that it shares specific antigenic determinants with CCHFV & NSDV. The Dugbe virus‘s nucleocapsid protein, the virus’s main structural protein, has been produced in insect cells and utilized as an antigen in serological assays. More research, however, is required to comprehend the antigenic diversity and development of the Dugbe virus and its related viruses.

The pathogenesis of the Dugbe virus (DUGV) involves several vital aspects. DUGV causes only a slight cytopathogenic effect when infecting mammalian cells, meaning it does not severely damage or destroy the host cells. In contrast, it does not cause any cytopathic effect in tick cells.

During the assembly of DUGV particles, budding takes place from the Golgi complex, a cellular organelle involved in protein processing and sorting. The DUGV glycoprotein G1 accumulates in vesicles derived from Golgi cisternae, indicating its involvement in the budding process. 

The nucleocapsid protein N, which encapsulates the viral genetic material, accumulates in scattered foci throughout the cytoplasm of infected cells. This pattern of distribution suggests a limited maturation of DUGV particles. 

The reduced number of budding virus particles observed in tick cells correlates with the reduced cytopathology observed. It indicates that DUGV has a less pronounced impact on tick cells than mammalian cells, potentially contributing to its ability to persist in ticks and maintain its transmission cycle. 

The deISGylating and deubiquitinating activity of the Dugbe virus likely contributes to its ability to evade the host immune system and establish a successful infection. By blocking key signaling pathways, the virus can disrupt the production of antiviral cytokines and the activation of immune cells, thereby suppressing the host’s antiviral defenses. 

Inflammatory response: 

When host cells detect the presence of Dugbe virus its components, they release TNF-α, which is a pro-inflammatory cytokine. TNF-α binds to its receptors on neighboring cells, triggering a signaling cascade that activates the nuclear factor-kappa B (NF-κB) pathway.

Activation of the NF-κB pathway leads to the translocation of NF-κB proteins from the cytoplasm to the nucleus of the host cells. In the nucleus, NF-κB performs as a transcription factor, enabling the function of several genes involved in immune responses and inflammation. These genes encode proteins such as cytokines, chemokines, adhesion molecules, and antimicrobial peptides, contributing to Dugbe virus elimination. 

Ubiquitination: 

Ubiquitination is a process in which ubiquitin molecules are covalently attached to target proteins, modulating their functions and fate within cells. In response to the Dugbe virus, ubiquitination can mark viral proteins or components for degradation by the proteasome, leading to their elimination from infected cells.

It helps to limit viral replication and spread. Secondly, ubiquitin chains can signal the activation of various immune pathways, including the NF-κB pathway. Ubiquitin-dependent signaling events can produce pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), which serves as a fundamental mechanism for orchestrating the antiviral innate immune response against the Dugbe virus. 

Antiviral defense reaction: 

In response to Dugbe virus infection, host cells release interferons that bind to specific receptors on neighboring cells, triggering a signaling cascade. ISG15 is an interferon-inducible protein that can be conjugated to various protein substrates through ISGylation, like ubiquitination.

The conjugation of ISG15 to its protein targets requires specific enzymes, including UBE1L as the E1-activating enzyme and UbcH8 as the E2-conjugating enzyme. Herc5, an E3 ligase, facilitates the transfer of ISG15 from the E2 enzyme to the target proteins. 

ISG15 is conjugated with several proteins involved in direct or indirect antiviral activity. These include RIG-I (Retinoic Acid-Inducible Gene I), a key sensor of viral RNA that initiates antiviral signaling pathways. ISG15 conjugation to RIG-I enhances its activity and promotes the production of antiviral cytokines.

Additionally, ISG15 can be conjugated to JAK1 (Janus Kinase 1) and STAT1 (Signal Transducer and Activator of Transcription 1), which are essential components of the interferon signaling pathway. ISG15 modification of these proteins enhances their stability and function, leading to an enhanced antiviral response.

Furthermore, ISG15 can also be conjugated with other proteins involved in antiviral defense, such as interferon regulatory factor 3 (IRF3) and protein kinase R (PKR). 

• Fever: Dugbe virus infection often presents with a sudden onset of fever, a hallmark symptom. The fever is usually high-grade and may be accompanied by chills. 

• Headache and body aches: Patients infected with the Dugbe virus commonly experience headaches and muscle or joint pain. These symptoms can be generalized or localized. 

• Gastrointestinal symptoms: Some individuals with Dugbe virus infection may develop gastrointestinal symptoms such as nausea, vomiting, and diarrhea. These symptoms can contribute to dehydration. 

• Rash: A maculopapular rash may sometimes develop on the skin. The rash can be generalized or localized and may appear during the illness. 

• Respiratory symptoms: Respiratory symptoms such as cough and sore throat can sometimes occur. However, respiratory symptoms are less prominent than other viral infections. 

• Neurological manifestations: Although less common, Dugbe virus infection can occasionally lead to neurological symptoms, including confusion, disorientation, and in severe cases, encephalitis or meningitis. 

Immunodiffusion test: In this test, tissue extracts from suspected cases or animal reservoirs are prepared and placed in wells cut into an agar gel plate. The hyperimmune antisera, produced by immunizing animals with DUGV antigens, are then added to the wells. If the tissue extract contains DUGV antigens, a reaction occurs between the viral antigens and the specific antibodies present in the antisera. It forms a visible precipitin line or band at the intersection between the antigen and antibody wells. The presence of a precipitin line indicates a positive result for DUGV infection. 

Gross pathologic examination: It is a diagnostic method used to assess the physical changes and abnormalities observed in tissues and organs during Dugbe virus (DUGV) infection. During this examination, the organs and tissues of interest, such as the liver, spleen, and lymph nodes, are visually inspected for any visible lesions or changes in color, texture, or size that may indicate infection.

Gross pathologic findings associated with DUGV infection can include congestion, hemorrhage, necrosis, enlargement of organs, and lymph node enlargement. These observations provide valuable information to the pathologist and help guide further diagnostic investigations. 

Electron microscopy: Patient samples such as blood, serum, or tissue specimens are prepared by fixing and embedding them in a suitable matrix. The samples are then thinly sectioned, typically around 50-100 nm thick, using a specialized instrument called an ultramicrotome. These ultrathin sections are mounted on a grid and stained with heavy metal stains, such as lead citrate and uranyl acetate, to enhance contrast and improve visualization.

The grids are placed inside an electron microscope, which directs an electron beam toward the samples. Electron contact with the specimen produces an image detected by a detector and presented on a monitor. The electron microscope captures high-resolution images of the DUGV particles, allowing them to be identified based on their morphology and size. 

• Implementing tick control strategies is crucial in reducing the risk of DUGV transmission. It includes measures such as applying acaricides (tick-killing agents) to livestock and agricultural areas to target tick populations. Regular inspection of animals and prompt removal of attached ticks can also help minimize exposure. 

• Applying insect repellents containing DEET or picaridin to exposed skin and using permethrin-treated clothing can also provide additional protection. 

Dugbe Virus – an overview | ScienceDirect Topics 

Studies on the pathogenicity of a nairovirus, Dugbe virus, in normal and immunosuppressed mice – PubMed (nih.gov)