Molecular Pathogenesis, Global Epidemiological Trends, and Treatment Strategies for Pteropine Orthoreoviruses: A Narrative Review

Figures

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  Figure 1.. Structure, classification, and host cell entry mechanism of Pteropine orthoreovirus (PRV). (A) Virion architecture: The PRV virion is a non-enveloped, double-layered icosahedral particle (60–80 nm in diameter). The outer capsid (composed of proteins such as σB and σC) mediates receptor binding and entry, while the inner capsid (core) encloses the ten segments of double-stranded RNA genomic material (categorized as Large/L, Medium/M, and Small/S segments) along with the viral RNA-dependent RNA polymerase. (B) Representative strains and zoonotic context: Key PRV strains (e.g. prototype Nelson Bay virus, human-pathogenic Melaka and Kampar viruses) are depicted in relation to their natural reservoir (fruit bats of the genus Pteropus) and the spillover event leading to human infection. (C) Heparan sulphate-mediated entry pathway: Viral attachment is initiated by the electrostatic interaction between the outer capsid proteins and negatively charged heparan sulphate proteoglycans on the host cell surface. Following heparan sulphate engagement and clustering, the virion is internalized via clathrin-mediated endocytosis, resulting in an internalized virion within an endosomal compartment,…

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  Figure 2.. Schematic representation of the cellular life cycle of Pteropine orthoreovirus (PRV). The PRV life cycle begins with viral attachment to heparan sulphate proteoglycans on the host cell surface via outer capsid proteins, followed by clathrin-mediated endocytosis. After partial capsid disassembly within endosomes, the transcriptionally active core is released into the cytoplasm, where viral double stranded RNA is transcribed and translated. Newly synthesized genomic segments are assembled into progeny virions. A key pathogenic feature is the expression of the non-structural p10 protein, which induces cell-cell fusion and syncytium formation, facilitating direct viral spread and immune evasion. Mature virions are subsequently released to initiate new rounds of infection. Created in BioRender. Ahmed, M. M. (2026) https://BioRender.com/d0dagnu.

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  Figure 3.. Zoonotic transmission pathways and integrated One Health surveillance framework for Pteropine orthoreoviruses (PRVs). The schematic illustrates the multi-host ecology, transmission pathways, and One Health surveillance framework of PRVs. Fruit bats of the family Pteropodidae serve as the primary reservoir hosts, maintaining asymptomatic viral circulation. Human spillover may occur through direct contact with bats or their excreta, environmental exposure to contaminated aerosols or fomites, consumption of contaminated food products, or via intermediate hosts such as macaques. Human infection can result in respiratory or neurological disease, with limited human-to-human transmission documented in some settings. The figure also highlights integrated surveillance and intervention strategies, including animal and environmental monitoring, clinical surveillance, laboratory diagnostics, public health education, habitat conservation, infection control measures, and rapid outbreak response. Laboratory confirmation and strain characterization are shown in outline only; the diagnostic assays and their clinical application are detailed in Figure 5. Created in BioRender. Ahmed, M. M. (2026)…

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  Figure 4.. Global distribution of Pteropine orthoreovirus (PRV) strains. Detections are shown on a Robinson projection of the Old World, against the approximate range of the pteropodid bat reservoir (shaded). Marker shape and colour indicate the class of evidence, and each marker is annotated with the strain reported at that site; Ghana and Bangladesh are annotated “no isolate named”, and Singapore “serosurvey only”, because no isolate is reported for those detections. Where sites coincide at this scale, markers are displaced by up to about two degrees so that each remains distinguishable. The concentration of detections in Southeast Asia reflects the distribution of surveillance and diagnostic capacity as well as that of the virus; absence of a marker indicates absence of published detection, not established absence of PRV. Compiled from Table 3; base map from Natural Earth.

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  Figure 5.. Clinical diagnostic workflow and therapeutic management of Pteropine orthoreovirus (PRV) infection. The algorithm outlines a multi-tiered diagnostic and management approach for suspected PRV infection. Patients presenting with acute respiratory illness or unexplained encephalitis, particularly with relevant exposure history, undergo specimen collection for molecular testing. Real time quantitative polymerase chain reaction targeting conserved PRV genomic regions enables rapid diagnosis, while serological assays and virus isolation provide confirmatory evidence when needed. Confirmed cases receive supportive care, and investigational therapies, including repurposed antivirals and host-targeted agents, are highlighted as potential treatment strategies. The surveillance context in which these assays are deployed is shown in Figure 3. Created in BioRender. Ahmed, M. M. (2026) https://BioRender.com/p5myfpx.