Uppala PK, Karanam SK, Kandra NV, Edhi S. Understanding machupo virus: A neglected arenavirus with global health importance. World J Virol 2026; 15(2): 119515 [DOI: 10.5501/wjv.v15.i2.119515]
Corresponding Author of This Article
Praveen Kumar Uppala, Assistant Professor, Researcher, Department of Pharmacology, Maharajah’s College of Pharmacy, Phool Baugh, Vizianagaram 535002, Andhra Pradesh, India. praveen.chintu32@gmail.com
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Virology
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Uppala PK, Karanam SK, Kandra NV, Edhi S. Understanding machupo virus: A neglected arenavirus with global health importance. World J Virol 2026; 15(2): 119515 [DOI: 10.5501/wjv.v15.i2.119515]
Praveen Kumar Uppala, Department of Pharmacology, Maharajah’s College of Pharmacy, Vizianagaram 535002, Andhra Pradesh, India
Sita Kumari Karanam, Department of Biotechnology, Maharajah’s College of Pharmacy, Vizianagaram 535002, Andhra Pradesh, India
Naga Vishnu Kandra, Department of Radiodiagnosis, Santhiram Medical College and General Hospital, Nandyal 518501, Andhra Pradesh, India
Sandhya Edhi, Department of Pharmacognosy, Andhra University College of Pharmaceutical Sciences, Visakhapatnam 530003, Andhra Pradesh, India
Author contributions: Uppala PK contributed to concept, design, drafting manuscript; Karanam SK contributed to final revision of manuscript; Kandra NV contributed to literature search; Edhi S contributed to literature search, design.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Praveen Kumar Uppala, Assistant Professor, Researcher, Department of Pharmacology, Maharajah’s College of Pharmacy, Phool Baugh, Vizianagaram 535002, Andhra Pradesh, India. praveen.chintu32@gmail.com
Received: February 2, 2026 Revised: February 22, 2026 Accepted: April 10, 2026 Published online: June 25, 2026 Processing time: 138 Days and 22.6 Hours
Abstract
Machupo virus (MACV), classified within the Mammarenavirus genus of the Arenaviridae family, serves as the causative agent of Bolivian hemorrhagic fever (BHF), a life-threatening zoonosis primarily confined to rural regions of Bolivia’s Beni Department. First identified in 1959 during epidemics in San Joaquín, this bisegmented, ambisense, single-stranded RNA virus exhibits 20%-35% case-fatality rates, with highest lethality among children under 5 and adults over 55. The vesper mouse (Calomys callosus) acts as the principal reservoir, sustaining lifelong asymptomatic infections and shedding virus through excreta, facilitating human spillover via aerosol inhalation, contaminated food, or direct contact-predominant in agrarian settings. Clinically, BHF follows a 5-21 days incubation with initial nonspecific febrile prodrome (fever, myalgia, prostration) evolving into hemorrhagic diathesis (petechiae, mucosal bleeds), neurological signs (tremors, delirium), leukopenia/thrombocytopenia, and shock. Pathogenesis hinges on transferrin receptor 1-mediated endothelial tropism, type I interferon suppression (NP/Z), and cytokine storms, recapitulated in guinea pig/primate models. Designated Centers for Disease Control and Prevention Category A and biosafety level (BSL)-4, MACV constrains research; diagnostics demand reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, or isolation in maximum containment. Supportive therapy prevails, augmented by off-label ribavirin (preclinical efficacy) and convalescent plasma; Candid 1 (Junín-attenuated) cross-protects informally. This review details MACV’s genomic organization (L/S segments encoding L/Z, NP/GPC), epidemiology, etiology, and advances: Reverse genetics for antivirals, GP-specific mAbs (100% guinea pig survival), multi-epitope vaccines, and high-throughput screening entry inhibitors. One health imperatives-rodent control, artificial intelligence surveillance, and Bolivian BSL-3 expansion-counter ecological drivers like deforestation. Amid climate, prioritizing global collaborations will forge resilient countermeasures, leveraging MACV as a sentinel for new world arenavirus threats.
Core Tip: Machupo virus, the etiological agent of Bolivian hemorrhagic fever, remains a neglected yet highly lethal arenavirus with significant biosafety and outbreak potential. This review integrates current knowledge on viral biology, transmission ecology, pathogenesis, diagnostics, and emerging countermeasures including monoclonal antibodies, antivirals, and next-generation vaccines. Strengthening one health surveillance and global research collaboration is essential to mitigate future spillover risks and improve preparedness against new world arenaviruses.
