Novel Human Reovirus Isolated from Children with Acute Necrotizing Encephalopathy

Ouattara, Louise A.; Barin, Françis; Barthez, M.; Bonnaud, Bertrand; Roingeard, Philippe; Goudeau, Alain; Castelnau, Pierre; Vernet, Guy; Paranhos-Baccalà, Gláucia; Komurian-Pradel, Florence

doi:10.3201/eid1708.101528

Cited by 79 publications

(89 citation statements)

References 33 publications

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“…The genomic segments of the orthoreoviruses are known to be susceptible to genetic reassortment and intragenic rearrangement [34, 35]. The exchange of RNA segments between viruses could lead to viral diversity, with increased virulence and an extended host range [36, 37]. Therefore, the reassortment of piscine orthoreoviruses must be clarified because PRV-2 and PRV infect the same hosts, including the coho salmon.…”

Section: Discussionmentioning

confidence: 99%

Full-Genome Sequencing and Confirmation of the Causative Agent of Erythrocytic Inclusion Body Syndrome in Coho Salmon Identifies a New Type of Piscine Orthoreovirus

Nawata²,

et al. 2016

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Erythrocytic inclusion body syndrome (EIBS) causes mass mortality in farmed salmonid fish, including the coho salmon, Onchorhynchus kisutchi, and chinook salmon, O. tshawytscha. The causative agent of the disease is a virus with an icosahedral virion structure, but this virus has not been characterized at the molecular level. In this study, we sequenced the genome of a virus purified from EIBS-affected coho salmon. The virus has 10 dsRNA genomic segments (L1, L2, L3, M1, M2, M3, S1, S2, S3, and S4), which closely resembles the genomic organization of piscine orthoreovirus (PRV), the causative agent of heart and skeletal inflammation (HSMI) in Atlantic salmon and HSMI-like disease in coho salmon. The genomic segments of the novel virus contain at least 10 open reading frames (ORFs): lambda 1 (λ1), λ2, λ3, mu 1 (μ1), μ2, μNS, sigma 1 (σ1), σ2, σ3, and σNS. An additional ORF encoding a 12.6-kDa protein (homologue of PRV p13) occurs in the same genomic segment as σ3. Phylogenetic analyses based on S1 and λ3 suggest that this novel virus is closely related to PRV, but distinctly different. Therefore, we designated the new virus ‘piscine orthoreovirus 2’ (PRV-2). Reverse transcription–quantitative real-time PCR revealed a significant increase in PRV-2 RNA in fish blood after the artificial infection of EIBS-naïve fish but not in that of fish that had recovered from EIBS. The degree of anemia in each fish increased as the PRV-2 RNA increased during an epizootic season of EIBS on an inland coho salmon farm. These results indicate that PRV-2 is the probable causative agent of EIBS in coho salmon, and that the host acquires immunity to reinfection with this virus. Further research is required to determine the host range of PRV species and the relationship between EIBS and HSMI in salmonid fish.

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Section: Discussionmentioning

confidence: 99%

Full-Genome Sequencing and Confirmation of the Causative Agent of Erythrocytic Inclusion Body Syndrome in Coho Salmon Identifies a New Type of Piscine Orthoreovirus

Nawata²,

et al. 2016

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“…Most mammals, including humans, are hosts for reovirus infection. While infection seldom results in human disease, rare cases of reovirus encephalitis in young children have been documented (Ouattara et al, 2011). Following peroral inoculation of newborn mice, reovirus is taken up by intestinal M cells and undergoes primary replication in gut-associated lymphoid tissue before accessing a variety of organs including the heart, liver, and brain (Morrison et al, 1991; Virgin et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

The Nogo Receptor NgR1 Mediates Infection by Mammalian Reovirus

Konopka-Anstadt

Mainou

Sutherland

et al. 2014

Cell Host & Microbe

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SUMMARY Neurotropic viruses, including mammalian reovirus, must disseminate from an initial site of replication to the central nervous system (CNS), often binding multiple receptors to facilitate systemic spread. Reovirus engages junctional adhesion molecule-A (JAM-A) to disseminate hematogenously. However, JAM-A is dispensable for reovirus replication in the CNS. We demonstrate that reovirus binds Nogo receptor NgR1, a leucine-rich-repeat protein expressed in the CNS, to infect neurons. Expression of NgR1 confers reovirus binding and infection of non-susceptible cells. Incubating reovirus virions with soluble NgR1 neutralizes infectivity. Blocking NgR1 on transfected cells or primary cortical neurons abrogates reovirus infection. Concordantly, reovirus infection is ablated in primary cortical neurons derived from NgR1-null mice. Reovirus virions bind to soluble JAM-A and NgR1, while infectious disassembly intermediates (ISVPs) bind only to JAM-A. These results suggest that reovirus uses different capsid components to bind distinct cell-surface molecules, engaging independent receptors to facilitate spread and tropism.

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“…Reoviruses infect most mammalian species, and although most humans are exposed during childhood, infection seldom results in disease (1, 2). The reovirus genome can now be engineered using reverse genetics, leading to the recovery of viable viruses with targeted alterations (3).…”

Section: Introductionmentioning

confidence: 99%

Reovirus Cell Entry Requires Functional Microtubules

Mainou

Zamora

Ashbrook

et al. 2013

mBio

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Mammalian reovirus binds to cell-surface glycans and junctional adhesion molecule A and enters cells by receptor-mediated endocytosis in a process dependent on β1 integrin. Within the endocytic compartment, reovirus undergoes stepwise disassembly, allowing release of the transcriptionally active viral core into the cytoplasm. To identify cellular mediators of reovirus infectivity, we screened a library of small-molecule inhibitors for the capacity to block virus-induced cytotoxicity. In this screen, reovirus-induced cell killing was dampened by several compounds known to impair microtubule dynamics. Microtubule inhibitors were assessed for blockade of various stages of the reovirus life cycle. While these drugs did not alter reovirus cell attachment or internalization, microtubule inhibitors diminished viral disassembly kinetics with a concomitant decrease in infectivity. Reovirus virions colocalize with microtubules and microtubule motor dynein 1 during cell entry, and depolymerization of microtubules results in intracellular aggregation of viral particles. These data indicate that functional microtubules are required for proper sorting of reovirus virions following internalization and point to a new drug target for pathogens that use the endocytic pathway to invade host cells.

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Novel Human Reovirus Isolated from Children with Acute Necrotizing Encephalopathy

Abstract: TOC summary line: This new virus may be another cause of encephalitis.

Cited by 79 publications

References 33 publications

Full-Genome Sequencing and Confirmation of the Causative Agent of Erythrocytic Inclusion Body Syndrome in Coho Salmon Identifies a New Type of Piscine Orthoreovirus

Full-Genome Sequencing and Confirmation of the Causative Agent of Erythrocytic Inclusion Body Syndrome in Coho Salmon Identifies a New Type of Piscine Orthoreovirus

The Nogo Receptor NgR1 Mediates Infection by Mammalian Reovirus

Reovirus Cell Entry Requires Functional Microtubules

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