Search Results (38)

Mammarenaviruses are enveloped, ambisense, single-stranded RNA viruses capable of causing fatal hemorrhagic fevers and severe neurological disorders in humans. Although muroid rodents have historically been recognized as the primary reservoirs for major pathogens like Lassa virus, recent surveillance has revealed a significant expansion of their host range. This review aims to synthesize current global data regarding the epidemiology of mammarenaviruses in conventional reservoirs and the emergence of novel arenaviruses in non-traditional mammalian hosts. To achieve this, we comprehensively analyzed recent molecular and metagenomic surveillance data, evolutionary studies, and epidemiological reports published worldwide. Key discoveries include Wenzhou virus in Asian house shrews, Plateau Pika virus in plateau pikas, and an independent, geographically clustered of hedgehog-associated arenaviruses across Europe. Ultimately, this review underscores the global distribution of these pathogens and the critical need for continued, multi-host surveillance worldwide. Full article

Viral hemorrhagic fevers (VHFs) are severe infectious diseases caused by RNA viruses of the families Arenaviridae, Filoviridae, Flaviviridae, and Hantaviridae, characterized by high morbidity, significant case fatality rates, and frequent diagnostic uncertainty in early disease stages. For military medical services, timely clinical recognition and laboratory confirmation are essential to guide patient management, prevent nosocomial transmission, and maintain operational continuity, particularly in endemic or resource-limited deployment settings. This review critically examines current diagnostic approaches to VHF-causative agents, emphasizing their use in clinical and field medical settings. The diagnostic process, from exposure through specimen collection, laboratory testing, and result interpretation is analyzed, including the use of molecular, serological, and antigen-based assays. Particular attention is given to deployable diagnostic platforms and their role in bridging the gap between frontline clinical suspicion and definitive laboratory confirmation. Biosafety requirements and infection prevention measures are discussed as integral components of clinical diagnostic workflows, aligned with guidance from the World Health Organization and the Centers for Disease Control and Prevention. Comparative analyses of virus-specific diagnostic timelines and laboratory requirements are presented to support differential diagnosis and clinical decision-making. Emerging technologies, including rapid molecular assays and genomic methods, are evaluated for their potential to improve early diagnosis and patient outcomes. This review highlights the central role of diagnostic readiness in clinical management of the VHFs and provides evidence-based considerations to support military clinicians facing high-risk febrile illnesses in operational environments. Full article

Machupo virus (MACV) is the causal agent of Bolivian Hemorrhagic fever. It is highly pathogenic, has a high mortality rate, and currently lacks specific treatments or vaccines. MACV belongs to the Arenaviridae family, which uses a cap-snatching mechanism during the transcription process. Its viral polymerase, the L protein, harbors the endonuclease activity required for cap snatching, making it a suitable target for the development of antiviral therapeutics. We combined experimental and computational methods to characterize MACV endonuclease activity and evaluate inhibitors. A fluorescence resonance energy transfer (FRET) assay was used to measure the enzymatic activity of endonuclease and identify potent inhibitors via high-throughput screening. FRET assays identified BW-148, an inhibitor with a 48.4 µM (95% CI: 37.3–59.3 µM; R² = 0.98) IC₅₀, and a K_D of 13.7 µM (95% CI: 8.2–19.2 µM, n = 3). Docking studies reveal that BW-148 may bind near the MACV endonuclease catalytic site, inhibiting enzymatic activities by metal chelating. BW-148 is a useful lead compound for further optimization of Machupo endonuclease inhibitors. Full article

Chapare virus (CHAPV) is an Arenaviridae family member and causative agent of Chapare hemorrhagic fever (CHHF). Endemic to Bolivia, CHAPV was found to be the cause of several outbreaks of CHHF in Bolivia in 2003 and 2019 with high case-fatality rates and instances of human-to-human transmission. The pathogenesis of CHAPV infection is poorly understood, and no vaccines or antivirals are available, in part due to a dearth of available animal models. Mice lacking signal transducer and activator of transcription 1 (STAT1^-/-) have been shown to succumb to infection by related arenaviruses, including Machupo virus, and were investigated for their susceptibility to CHAPV infection. Challenge with CHAPV resulted in partial lethality in STAT1^-/- mice with a biphasic disease course characterized by initial viral load and pathology in the spleen and liver followed by inflammation and high viral titers in the brain and spinal cord that immediately preceded mortality. Adaptation in the brains of STAT1^-/- mice resulted in a fully lethal mouse-adapted CHAPV variant, with a similar biphasic disease course, but virus in tissues was detected more proximal to challenge. The result of this study is a lethal small-animal rodent model for CHAPV that recapitulates many aspects of human CHAPV disease. Full article

Lassa virus (LASV), a member of the Arenaviridae family, is the causative agent of Lassa fever (LF), an acute zoonotic hemorrhagic disease transmitted by rodents, characterized by high infectivity and mortality rates. Due to the nonspecific nature of early clinical symptoms, the development of rapid, sensitive, and specific diagnostic methods is critical for effective epidemic control. In this study, the Lassa virus glycoprotein complex (LASV-G) was selected as the target antigen. High-affinity rabbit monoclonal antibodies were generated using a single B-cell cloning approach, and an AlphaLISA (Amplified Luminescent Proximity Homogeneous Assay)-based homogeneous, no-wash detection system was established. Sixteen LASV-G-specific monoclonal antibodies were isolated through flow cytometric sorting, and the optimal antibody pair (56–24) was identified by AlphaLISA pairing and performance screening. The established AlphaLISA system exhibited a limit of detection (LOD) of 0.025 ng/mL, representing approximately a 30-fold increase in sensitivity compared with conventional Enzyme Linked Immunosorbent Assay (ELISA), while reducing the total assay time to less than 30 min. The coefficient of variation (CV) was below 8%, and no cross-reactivity was observed with Ebola, dengue, yellow fever, Zika, or influenza virus antigens. These findings demonstrate that the developed AlphaLISA assay possesses high sensitivity, rapid detection, and good tolerance to matrix effects, significantly improving the efficiency of early LASV antigen detection. This work provides a potential platform for the rapid on-site screening and epidemiological surveillance of highly pathogenic viruses. Full article

The family Arenaviridae encompasses zoonotic, rodent-borne pathogens (e.g., Lassa, Machupo, and Junín viruses) that cause severe viral hemorrhagic fevers with high case fatality rates. The current therapeutic landscape is severely limited, underscoring the urgent need for novel antiviral strategies. A promising approach involves combining directly acting antivirals with host-targeted antivirals. A compelling host-targeted antiviral target is the aryl hydrocarbon receptor (AHR). This ubiquitous ligand-activated transcription factor is a recognized pro-viral host factor across multiple viral families. Building on prior work with Junín and Tacaribe viruses, we investigated whether the AHR inhibitor CH223191 could enhance the virus-directed antiviral activity of favipiravir against these viruses. First, we evaluated the toxicity and antiviral potential of CH223191 against a lethal Junín virus infection in male and female hTfR1 mice. After demonstrating substantial protection, we conducted preliminary assays to study the antiviral effects of combining CH223191 and favipiravir on Tacaribe virus (TCRV) infections in the Vero cell culture model. We observed synergistic interaction with all four models (ZIP, Loewe, Bliss, and HSA). We next determined the sub-optimal dose of favipiravir and conducted an antiviral combination study in the AG129 mouse model infected with TCRV. The combination effectively protected mice from a lethal TCRV infection and showed cooperative effects, reducing weight loss and viral loads. Overall, these results show that the AHR is a promising pharmacological target for the development of novel antivirals. Furthermore, we discovered a cooperative interaction between the activities of favipiravir and CH223191. Full article

Introduction: Despite the impressive progress carried out in the field of biomedical sciences in recent decades, the incidence of emerging and neglected lethal viral infections mainly belonging to the Coronaviridae, Filoviridae, Arenaviridae, Bunyaviridae, and Paramyxoviridae families has considerably impaired human health. The worldwide vaccination campaign at the end of the 1970s determined the eradication of smallpox. However, the growing number of cases of diseases linked to orthopoxvirus diseases, such as the recent epidemic of monkeypox zoonosis in various countries around the world, has increased the need for knowledge of these viral pathogens. To date, there is no specific treatement for Monkeypox virus (MPXV) infection. However, several antiviral drugs used to treat Smallpox and other viral infections could also be beneficial for Monkeypox disease. In this study we report the design and synthesis of new, variously substituted benzimidazole derivatives and the evaluation of their cytotoxicity and antiviral activity against representatives of the Orthopoxvirus genus, Vaccinia Virus (VV), closely related to variola virus and MPXV. Methods: A combination of cell-based assays and experimental techniques was used to investigate the cytotoxicity, antiviral activity, and mechanisms of action of the most interesting compound. Results: In our study, new, variously substituted benzimidazoles showed interesting EC₅₀ values against vaccinia and MPXV and a cytotoxic profile in the high micromolar range. Conclusions: Our work shows that the new tested benzimidazole derivatives possess appealing activity and selectivity, accompanied by low cytotoxicity. These results set a valid foundation with which to identify potent and selective anti-Poxvirus agents. Full article

Machupo virus (MACV), a member of the Arenaviridae family and causative agent of Bolivian hemorrhagic fever, results in lethality rates of 25–35% in humans. Mice lacking the signal transducer and activator of transcription 1 (STAT-1^−/−) have previously been shown to succumb to MACV infection within 7–8 days via the intraperitoneal route. Despite these reports, we observed partial lethality in STAT-1^−/− mice following challenge with wild-type MACV. Serial sampling studies to evaluate the temporal progression of infection and pathologic changes after challenge revealed a two-phase disease course. The first phase was characterized by viral load and pathological lesions in the spleen, liver, and kidney followed by a second, lethal phase, defined by high viral titers and inflammation in the brain and spinal cord resulting in neurological manifestations and subsequent mortality. Tissue adaptation in the brains of challenged STAT-1^−/− mice resulted in a fully lethal model in STAT-1^−/− mice (mouse-adapted; maMACV). A similar two-phase disease course was observed following maMACV challenge, but more rapid dissemination of the virus to the brain and overall pathology in this region was observed. The outcome of these studies is a lethal small rodent model of MACV that recapitulates many aspects of human disease. Full article

Rodents represent the most diverse order of mammals, comprising over 2200 species and nearly 42% of global mammalian biodiversity. They are major reservoirs of zoonotic pathogens, including viruses, bacteria, protozoa, and fungi, and are particularly effective at transmitting diseases, especially synanthropic species that live in close proximity to humans. As of April 2025, approximately 15,205 rodent-associated viruses have been identified across 32 viral families. Among these, key zoonotic agents belong to the Arenaviridae, Hantaviridae, Picornaviridae, Coronaviridae, and Poxviridae families. Due to their adaptability to both urban and rural environments, rodents serve as efficient vectors across diverse ecological landscapes. Environmental and anthropogenic factors, such as climate change, urbanization, deforestation, and emerging pathogens, are increasingly linked to rising outbreaks of rodent-borne diseases. This review synthesizes current knowledge on rodent-borne viral zoonoses, focusing on their taxonomy, biology, host associations, transmission dynamics, clinical impact, and public health significance. It underscores the critical need for early detection, effective surveillance, and integrated control strategies. A multidisciplinary approach, including enhanced vector control, improved environmental sanitation, and targeted public education, is essential for mitigating the growing threat of rodent-borne zoonoses to global health. Full article

Human activities and land use changes have a major impact on the distribution and diversity of mosquito vectors and their associated viruses. This study describes the diversity and differential abundance of viruses associated with mosquito species from four habitats of the Yucatan Peninsula, Mexico. Using next-generation sequencing (NGS), we analyzed 61 genomic libraries belonging to 20 mosquito species to characterize the viral community. A total of 16 viral species were identified, representing 14 different viral families. Most identified viruses were associated with insects, plants, and fungi. Additionally, vertebrate associated viral families, including Herpesviridae, Peribunyaviridae, Nairoviridae, and Arenaviridae, were detected in mosquitoes from urban habitats. Notably, insect-associated viruses like Hubei mosquito virus 4 and Hubei virga-like virus 2 were identified, along with the first report of Mercadeo virus in Mexico. Variations in viral community composition were primarily driven by mosquito species, with species of the same genus maintaining similar viromes despite occupying different habitats. These findings reinforce that intrinsic traits of mosquito species play a key role in shaping viral community composition. To our knowledge, this is the first study that describes the viral community in mosquitoes in Yucatan Peninsula, Mexico. This study provides essential baseline data for the surveillance of mosquitoes and associated viruses from a biodiverse tropical region that faces strong land use modifications. Full article

Lassa mammarenavirus (LASV), a member of the family Arenaviridae, is a highly pathogenic virus capable of causing severe systemic infections in humans. The primary host reservoir is the Natal multimammate mouse (Mastomys natalensis), with human infections typically occurring through mucosal exposure to virus-containing aerosols from rodent excretions. To better understand the molecular mechanisms underlying LASV replication in the respiratory tract, we utilized differentiated primary human airway epithelial cells (HAECs) grown under air–liquid interface conditions, closely mimicking the bronchial epithelium in vivo. Our findings demonstrate that HAECs are permissive to LASV infection and support productive virus replication. While LASV entry into polarized HAECs occurred through both apical and basolateral surfaces, progeny virus particles were predominantly released from the apical surface, consistent with an intrinsic apical localization of the envelope glycoprotein GP. This suggests that apical virus shedding from infected bronchial epithelia may facilitate LASV transmission via airway secretions. Notably, limited basolateral release at later stages of infection was associated with LASV-induced rearrangement of the actin cytoskeleton, resulting in compromised epithelial barrier integrity. Finally, we demonstrate that LASV-infected HAECs exhibited a pronounced type III interferon response. A detailed understanding of LASV replication and host epithelial responses in the respiratory tract could facilitate the development of targeted future therapeutics. Full article

Zoonotic viruses may be neglected as etiologies of meningoencephalitis in humans. We performed retrospective testing of cerebrospinal fluid from encephalitis cases in biobank material for three zoonotic or potentially zoonotic viruses: rustrela virus (Rubivirus strelense, Matonaviridae); Tahyna virus (Orthobunyavirus tahynaense, Peribunyaviridae); and lymphocytic choriomeningitis virus (“LCMV”, Mammarenavirus choriomeningitidis, Arenaviridae). The cohort consisted of 443 samples, received for routine diagnostic testing year-round between January 2019 and February 2023, and were negative for herpes simplex viruses, varicella zoster virus, and enteroviruses. Using published RT-qPCR protocols, we did not detect rustrela virus or Tahyna virus in any sample. Using a herein described RT-qPCR protocol, we detected LCMV in one sample. Partial genetic sequencing of the virus suggested that the virus was locally acquired. Our study provides information about the incidence of these viruses in humans in Austria when encephalitis is suspected. Full article

Viral haemorrhagic fevers encompass a diverse group of severe, often life-threatening illnesses caused by viruses from multiple families, including Arenaviridae, Filoviridae, Flaviviridae, Hantaviridae, Nairoviridae, Peribunyaviridae, and Phenuiviridae. Characterised by fever and haemorrhagic symptoms, these diseases challenge public health systems by overwhelming healthcare facilities, complicating diagnostic processes, and requiring extensive resources for containment and treatment, especially in resource-limited settings. This discussion explores the intricate relationships between VHFs and their transmission vectors—both animal and arthropod—and examines the impact of ecological and geographic factors on disease spread. The primary transmission of VHFs typically occurs through direct contact with infected animals or via bites from haematophagous arthropods, facilitating zoonotic and, at times, human-to-human transmission. With an emphasis on the role of diverse wildlife, domesticated animals, and vectors such as mosquitoes and ticks in the epidemiology of VHFs, there is a recognised need for robust surveillance and strategic public health responses to manage outbreaks. This review discusses the necessity of interdisciplinary approaches that integrate virology, ecology, and public health to enhance diagnostic capabilities, develop vaccines and antivirals, and improve outbreak interventions. Exploring the ecological and biological dynamics of VHFs will help bolster a deeper understanding of these emerging viruses and underpin preparation for future outbreaks. The importance of enhanced global cooperation, continuous research, and collaboration to mitigate the public health threats posed by these complex infections is a central theme, serving as a foundational strategy to reinforce worldwide preparedness and response efforts. Future directions include addressing gaps in vaccine development and tailoring public health strategies to the unique challenges of managing VHFs, such as the rapid mutation rates of viruses, the need for cold chain logistics for vaccine distribution, and socio-economic barriers to healthcare access, in order to ensure readiness for and effective response to emerging threats worldwide. Full article

Shrews (Soricidae) are common small wild mammals. Some species of shrews, such as Asian house shrews (Suncus murinus), have a significant overlap in their habitats with humans and domestic animals. Currently, over 190 species of viruses in 32 families, including Adenoviridae, Arenaviridae, Arteriviridae, Astroviridae, Anelloviridae, Bornaviridae, Caliciviridae, Chuviridae, Coronaviridae, Filoviridae, Flaviviridae, Hantaviridae, Hepadnaviridae, Hepeviridae, Nairoviridae, Nodaviridae, Orthoherpesviridae, Orthomyxoviridae, Paramyxoviridae, Parvoviridae, Phenuiviridae, Picobirnaviridae, Picornaviridae, Polyomaviridae, Poxviridae, Rhabdoviridae, Sedoreoviridae, Spinareoviridae, and three unclassified families, have been identified in shrews. Diverse shrew viruses, such as Borna disease virus 1, Langya virus, and severe fever with thrombocytopenia syndrome virus, cause diseases in humans and/or domestic animals, posing significant threats to public health and animal health. This review compiled fundamental information about shrews and provided a comprehensive summary of the viruses that have been detected in shrews, with the aim of facilitating a deep understanding of shrews and the diversity, epidemiology, and risks of their viruses. Full article

Odontogenic bone tumor (OT) is a rare pathology in the world, but it is very common in developing countries; its etiology is still unknown, and it causes serious deformities of the mandible and maxilla if it is not operated upon soon. Lassa virus (LASV) belongs to the Arenaviridae family, and its reservoir is a rodent of the genus Mastomys. The transmission of the LASV to humans can occur through ingestion or inhalation by contact with dirty objects, the consumption of contaminated food, or exposure to wounds, as rodents shed the virus in their urine and excrement. In this observational study, we aim to evaluate the presence of LASV in OT patient tissues collected in the Democratic Republic of the Congo. For this purpose, a group of nine patients affected by OT were enrolled, and the tissues derived from the surgery were collected. In total, 81.5% of the tissues were positive for LASV presence. Interestingly, we found that not only was the tumor LASV-positive, but in some cases, the bone was close to the tumor and the oral mucosa lining. These preliminary data could suggest the hypothesis that LASV may be involved with the onset of OT. Full article