Zoonotic Potential of Avian Orthoreovirus (ARV): A Comprehensive Review

Zoonotic Potential of Avian Orthoreovirus (ARV): A Comprehensive Review Abstract Avian orthoreoviruses (ARVs) are double-stranded RNA viruses that infect a wide variety of avian species, causing arthritis, tenosynovitis, enteritis, and growth retardation in poultry. While ARV is well-established as a pathogen in birds, its potential to infect humans has become an emerging question in light of increasing human-animal interfaces. ARVs share structural and genomic similarities with mammalian orthoreoviruses (MRVs), some of which are known to infect humans. Despite this, no confirmed human cases of ARV infection have been reported. This review evaluates the genetic, molecular, and ecological factors influencing the zoonotic potential of ARV, drawing comparisons with known zoonotic orthoreoviruses such as Melaka virus and Nelson Bay virus. The likelihood of ARV spillover to humans is currently considered low, but continued genomic evolution and reassortment events warrant vigilance and sustained surveillance. 1. Introduction The genus Orthoreovirus within the family Reoviridae includes non-enveloped viruses with segmented double-stranded RNA genomes. Among these, Avian orthoreovirus (ARV) predominantly infects chickens, turkeys, ducks, and wild birds, causing significant economic losses in the poultry industry (Benavente & Martínez-Costas, 2007). Although ARVs are primarily host-restricted, the history of zoonotic transitions in other reoviruses raises questions about their potential to infect humans. For instance, mammalian orthoreoviruses (MRVs) and bat-borne orthoreoviruses such as Melaka virus and Kampar virus have demonstrated cross-species transmission (Chua et al., 2008).This review synthesizes available evidence on ARV biology, host range, molecular evolution, and assesses its zoonotic potential. 2. Biology and Structure of Avian Orthoreovirus ARV is a non-enveloped, icosahedral virus, approximately 70–80 nm in diameter. It contains ten segments of double-stranded RNA that encode structural (λ, μ, σ) and non-structural proteins (σNS, μNS) (Shmulevitz & Duncan, 2000). Its segmented genome facilitates genetic reassortment — a key mechanism behind viral evolution and emergence of novel strains (Zhang et al., 2021). The viral attachment protein σC mediates cell entry and determines host specificity (Guardado-Calvo & Rey, 2017). Any mutation or reassortment in σC that enhances affinity for human cell receptors could theoretically expand host range, a mechanism similar to zoonotic orthoreoviruses identified in bats. 3. Epidemiology and Host Range ARV infections have been detected globally across poultry-producing regions. The virus is transmitted horizontally via fecal-oral and respiratory routes, with occasional vertical transmission through eggs (Benavente & Martínez-Costas, 2007). Although ARV primarily infects avian species, its ability to infect avian cell lines from multiple species (including ducks, geese, and pigeons) indicates a relatively broad avian host range (Zhang et al., 2021). However, to date there are no documented natural infections of humans or mammals with ARV (Cornell Wildlife Health Lab, 2023). Experimental studies show that ARV replication in mammalian cells is poor or absent, suggesting strong host-range restriction (Rathgeber et al., 2017). 4. Comparison with Known Zoonotic Orthoreoviruses Several members of the Orthoreovirus genus have crossed species barriers: Virus Origin Known Human Infection Clinical Signs Mammalian orthoreovirus (MRV) Various mammals Yes (sporadic) Mild enteric, respiratory infections Melaka virus Bats (Pteropus spp.) Yes (Malaysia, 2007) Fever, respiratory illness Kampar virus Bats Yes (Malaysia, 2008) Flu-like symptoms Nelson Bay virus Bats Yes (Australia, 1970) Mild respiratory illness Avian orthoreovirus (ARV) Birds No Not reported Table 1. Comparative zoonotic potential among orthoreoviruses. The zoonotic orthoreoviruses share high sequence similarity in conserved regions (λA and σC genes) with ARV, suggesting evolutionary relatedness (Chua et al., 2008; Kohl et al., 2012). However, ARV remains avian-restricted possibly due to receptor incompatibility and innate immune barriers in mammals. 5. Molecular Basis of Zoonotic Potential 5.1 Genetic Plasticity and Reassortment ARV’s segmented genome allows reassortment between strains during co-infection, producing antigenic diversity and occasionally new phenotypes (Zhang et al., 2021). Theoretical risk arises if co-infection occurs between ARV and mammalian orthoreoviruses in a shared environment (e.g., poultry farms near wild mammals). Such reassortment could yield hybrid strains with altered host range. 5.2 Receptor Usage The ARV σC protein mediates binding to avian cell receptors. Studies suggest it interacts with sialic acid residues specific to avian cells (Guardado-Calvo & Rey, 2017). Human cells may lack compatible receptor configurations, preventing viral entry. Adaptation to human receptors, as seen in influenza A spillovers, could change this dynamic. 5.3 Immune Evasion Mammalian orthoreoviruses can evade interferon responses using non-structural proteins like σ3 and μNS (Zurney et al., 2009). ARV encodes similar proteins, raising the possibility that minor sequence adaptations could facilitate immune evasion in human hosts. 6. Ecological and Occupational Risk Factors High exposure environments — such as poultry farms, live-bird markets, and processing plants — are key ecological interfaces for potential ARV spillover (Lee et al., 2019). The global increase in poultry production intensifies human-bird contact, which may promote cross-species viral adaptation. Workers handling infected poultry could be asymptomatically exposed, but no serological evidence of infection has been found to date (Rathgeber et al., 2017). Environmental persistence of ARV is another concern; as a non-enveloped virus, it can survive for extended periods on surfaces, increasing the opportunity for cross-species contact (Benavente & Martínez-Costas, 2007). 7. Surveillance and Research Gaps Although the risk appears low, several gaps remain: Lack of systematic serological surveys among poultry workers and veterinarians. Limited receptor characterization studies for σC–host interactions. Absence of cross-infection models using mammalian cell lines or small animal models. Need for genomic surveillance to track ARV reassortment with other reoviruses. Enhanced molecular surveillance and next-generation sequencing in both poultry and wild bird populations are essential for early detection of potentially zoonotic ARV strains. 8. Conclusion Avian orthoreovirus remains an avian-restricted pathogen with no known human infections. However, its genetic flexibility, segmented RNA genome, and evolutionary relatedness to zoonotic orthoreoviruses highlight the importance of continued vigilance. While current evidence indicates a low probability of ARV becoming a human pathogen, ecological and molecular factors could, over time, alter this risk. 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