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  1. Pritchard LI, Chua KB, Cummins D, Hyatt A, Crameri G, Eaton BT, et al.
    Arch Virol, 2006 Feb;151(2):229-39.
    PMID: 16205863
    After the outbreak of Nipah virus (NiV) in 1998-99, which resulted in 105 human deaths and the culling of more than one million pigs, a search was initiated for the natural host reservoir of NiV on Tioman Island off the east coast of Malaysia. Three different syncytia-forming viruses were isolated from fruit bats on the island. They were Nipah virus, Tioman virus (a novel paramyxovirus related to Menangle virus), and a reovirus, named Pulau virus (PuV), which is the subject of this study. PuV displayed the typical ultra structural morphology of a reovirus and was neutralised by serum against Nelson Bay reovirus (NBV), a reovirus isolated from a fruit bat (Pteropus poliocephalus) in Australia over 30 years ago. PuV was fusogenic and formed large syncytia in Vero cells. Comparison of dsRNA segments between PuV and NBV showed distinct mobility differences for the S1 and S2 segments. Complete sequence analysis of all four S segments revealed a close relationship between PuV and NBV, with nucleotide sequence identity varying from 88% for S3 segment to 56% for the S1 segment. Similarly phylogenetic analysis of deduced protein sequences confirmed that PuV is closely related to NBV. In this paper we discuss the similarities and differences between PuV and NBV which support the classification of PuV as a novel mammalian, fusogenic reovirus within the Nelson Bay orthoreovirus species, in the genus Orthoreovirus, family Reoviridae.
    Matched MeSH terms: Orthoreovirus, Mammalian/classification*; Orthoreovirus, Mammalian/genetics; Orthoreovirus, Mammalian/isolation & purification*
  2. Siew ZY, Tan YF, Iswara RP, Wong SF, Wong ST, Tan BK, et al.
    Microbes Infect, 2024;26(1-2):105243.
    PMID: 38380604 DOI: 10.1016/j.micinf.2023.105243
    Pteropine orthoreovirus (PRV) causes respiratory tract infections in humans. Despite its emergence as a zoonotic and respiratory virus, little is known about its cell tropism, which hampers progress in fully understanding its pathogenesis in humans. Hek293 cells are most susceptible to PRV infection, while HeLa cells are the least. Human cytokeratin 1 (CK1) was identified as the protein that interacts with PRV. The immunofluorescence assay and qPCR results revealed prior treatment with anti-CK1 may provide Hek293 cells protection against PRV. The KRT1-knockout Hek293 cells were less susceptible to PRV infection. Further study into the pathogenesis of PRV in humans is needed.
    Matched MeSH terms: Orthoreovirus*
  3. Lorusso A, Teodori L, Leone A, Marcacci M, Mangone I, Orsini M, et al.
    Infect Genet Evol, 2015 Mar;30:55-58.
    PMID: 25497353 DOI: 10.1016/j.meegid.2014.12.006
    A novel member of the Pteropine Orthoreovirus species has been isolated and sequenced for the whole genome from flying foxes (Pteropus vampyrus) imported to Italy from Indonesia. The new isolate named Indonesia/2010 is genetically similar to Melaka virus which has been the first virus of this species to be shown to be responsible for human respiratory disease. Our findings highlight the importance of flying foxes as vectors of potentially zoonotic viruses and the biological hazard that lies in the import of animals from geographical areas that are ecologically diverse from Europe.
    Matched MeSH terms: Orthoreovirus/classification*; Orthoreovirus/genetics*; Orthoreovirus/isolation & purification
  4. Voon K, Chua KB, Yu M, Crameri G, Barr JA, Malik Y, et al.
    J Gen Virol, 2011 Dec;92(Pt 12):2930-2936.
    PMID: 21849518 DOI: 10.1099/vir.0.033498-0
    We previously described three new Malaysian orthoreoviruses designated Pulau virus, Melaka virus and Kampar virus. Melaka and Kampar viruses were shown to cause respiratory disease in humans. These viruses, together with Nelson Bay virus, isolated from Australian bats, are tentatively classified as different strains within the species Pteropine orthoreovirus (PRV), formerly known as Nelson Bay orthoreovirus, based on the small (S) genome segments. Here we report the sequences of the large (L) and medium (M) segments, thus completing the whole-genome characterization of the four PRVs. All L and M segments were highly conserved in size and sequence. Conserved functional motifs previously identified in other orthoreovirus gene products were also found in the deduced proteins encoded by the cognate segments of these viruses. Detailed sequence analysis identified two genetic lineages divided into the Australian and Malaysian PRVs, and potential genetic reassortment among the M and S segments of the three Malaysian viruses.
    Matched MeSH terms: Orthoreovirus/classification; Orthoreovirus/genetics*; Orthoreovirus/isolation & purification
  5. Yamanaka A, Iwakiri A, Yoshikawa T, Sakai K, Singh H, Himeji D, et al.
    PLoS One, 2014;9(3):e92777.
    PMID: 24667794 DOI: 10.1371/journal.pone.0092777
    A Japanese man suffered from acute respiratory tract infection after returning to Japan from Bali, Indonesia in 2007. Miyazaki-Bali/2007, a strain of the species of Nelson Bay orthoreovirus, was isolated from the patient's throat swab using Vero cells, in which syncytium formation was observed. This is the sixth report describing a patient with respiratory tract infection caused by an orthoreovirus classified to the species of Nelson Bay orthoreovirus. Given the possibility that all of the patients were infected in Malaysia and Indonesia, prospective surveillance on orthoreovirus infections should be carried out in Southeast Asia. Furthermore, contact surveillance study suggests that the risk of human-to-human infection of the species of Nelson Bay orthoreovirus would seem to be low.
    Matched MeSH terms: Orthoreovirus*
  6. Chua KB, Voon K, Crameri G, Tan HS, Rosli J, McEachern JA, et al.
    PLoS One, 2008;3(11):e3803.
    PMID: 19030226 DOI: 10.1371/journal.pone.0003803
    First discovered in the early 1950s, reoviruses (respiratory enteric orphan viruses) were not associated with any known disease, and hence named orphan viruses. Recently, our group reported the isolation of the Melaka virus from a patient with acute respiratory disease and provided data suggesting that this new orthoreovirus is capable of human-to-human transmission and is probably of bat origin. Here we report yet another Melaka-like reovirus (named Kampar virus) isolated from the throat swab of a 54 year old male patient in Kampar, Perak, Malaysia who was suffering from high fever, acute respiratory disease and vomiting at the time of virus isolation. Serological studies indicated that Kampar virus was transmitted from the index case to at least one other individual and caused respiratory disease in the contact case. Sequence analysis of the four small class genome segments indicated that Kampar and Melaka viruses are closely related. This was confirmed by virus neutralization assay, showing an effective two-way cross neutralization, i.e., the serum against one virus was able to neutralize the other. Although the exact origin of Kampar virus is unknown, epidemiological tracing revealed that the house of the index case is surrounded by fruit trees frequently visited by fruit bats. There is a high probability that Kampar virus originated from bats and was transmitted to humans via bat droppings or contaminated fruits. The discovery of Kampar virus highlights the increasing trend of emergence of bat zoonotic viruses and the need to expand our understanding of bats as a source of many unknown viruses.
    Matched MeSH terms: Orthoreovirus/isolation & purification*
  7. Chua KB, Crameri G, Hyatt A, Yu M, Tompang MR, Rosli J, et al.
    Proc Natl Acad Sci U S A, 2007 Jul 03;104(27):11424-9.
    PMID: 17592121
    Respiratory infections constitute the most widespread human infectious disease, and a substantial proportion of them are caused by unknown etiological agents. Reoviruses (respiratory enteric orphan viruses) were first isolated from humans in the early 1950s and so named because they were not associated with any known disease. Here, we report a previously unknown reovirus (named "Melaka virus") isolated from a 39-year-old male patient in Melaka, Malaysia, who was suffering from high fever and acute respiratory disease at the time of virus isolation. Two of his family members developed similar symptoms approximately 1 week later and had serological evidence of infection with the same virus. Epidemiological tracing revealed that the family was exposed to a bat in the house approximately 1 week before the onset of the father's clinical symptoms. Genome sequence analysis indicated a close genetic relationship between Melaka virus and Pulau virus, a reovirus isolated in 1999 from fruit bats in Tioman Island, Malaysia. Screening of sera collected from human volunteers on the island revealed that 14 of 109 (13%) were positive for both Pulau and Melaka viruses. This is the first report of an orthoreovirus in association with acute human respiratory diseases. Melaka virus is serologically not related to the different types of mammalian reoviruses that were known to infect humans asymptomatically. These data indicate that bat-borne reoviruses can be transmitted to and cause clinical diseases in humans.
    Matched MeSH terms: Orthoreovirus, Mammalian/classification; Orthoreovirus, Mammalian/isolation & purification*; Orthoreovirus, Mammalian/pathogenicity
  8. Mok L, Wynne JW, Grimley S, Shiell B, Green D, Monaghan P, et al.
    J Gen Virol, 2015 Jul;96(Pt 7):1787-94.
    PMID: 25748429 DOI: 10.1099/vir.0.000112
    In recent years, bats have been identified as a natural reservoir for a diverse range of viruses. Nelson Bay orthoreovirus (NBV) was first isolated from the heart blood of a fruit bat (Pteropus poliocephalus) in 1968. While the pathogenesis of NBV remains unknown, other related members of this group have caused acute respiratory disease in humans. Thus the potential for NBV to impact human health appears plausible. Here, to increase our knowledge of NBV, we examined the replication and infectivity of NBV using different mammalian cell lines derived from bat, human, mouse and monkey. All cell lines supported the replication of NBV; however, L929 cells showed a greater than 2 log reduction in virus titre compared with the other cell lines. Furthermore, NBV did not induce major cytopathic effects in the L929 cells, as was observed in other cell lines. Interestingly, the related Pteropine orthoreoviruses, Pulau virus (PulV) and Melaka virus (MelV) were able to replicate to high titres in L929 cells but infection resulted in reduced cytopathic effect. Our study demonstrates a unique virus-host interaction between NBV and L929 cells, where cells effectively control viral infection/replication and limit the formation of syncytia. By elucidating the molecular mechanisms that control this unique relationship, important insights will be made into the biology of this fusogenic virus.
    Matched MeSH terms: Orthoreovirus/growth & development; Orthoreovirus/physiology*
  9. Hu T, Qiu W, He B, Zhang Y, Yu J, Liang X, et al.
    BMC Microbiol, 2014;14:293.
    PMID: 25433675 DOI: 10.1186/s12866-014-0293-4
    In recent years novel human respiratory disease agents have been described for Southeast Asia and Australia. The causative pathogens were classified as pteropine orthoreoviruses with a strong phylogenetic relationship to orthoreoviruses of bat origin.
    Matched MeSH terms: Orthoreovirus/genetics*; Orthoreovirus/isolation & purification*
  10. Kosoltanapiwat N, Reamtong O, Okabayashi T, Ampawong S, Rungruengkitkun A, Thiangtrongjit T, et al.
    BMC Microbiol, 2018 10 17;18(1):135.
    PMID: 30332986 DOI: 10.1186/s12866-018-1302-9
    BACKGROUND: The pteropine orthoreovirus (PRV) was isolated from monkey (Macaca fascicularis) faecal samples collected from human-inhabited areas in Lopburi Province, Thailand. These samples were initially obtained to survey for the presence of hepatitis E virus (HEV).

    RESULTS: Two virus isolates were retrieved by virus culture of 55 monkey faecal samples. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was successfully used to identify the viruses as the segmented dsRNA orthoreovirus. Phylogenetic analysis of the Lopburi orthoreovirus whole-genomes revealed relationships with the well-characterised PRVs Pulau (segment L1), Cangyuan (segments L2, M3 and S3), Melaka (segments L3 and M2), Kampar (segments M1 and S2) and Sikamat (segments S1 and S4) of Southeast Asia and China with nucleotide sequence identities of 93.5-98.9%. RT-PCR showed that PRV was detected in 10.9% (6/55) and HEV was detected in 25.5% (14/55) of the monkey faecal samples.

    CONCLUSIONS: PRV was isolated from monkey faeces for the first time in Thailand via viral culture and LC-MS/MS. The genetic diversity of the virus genome segments suggested a re-assortment within the PRV species group. The overall findings emphasise that monkey faeces can be sources of zoonotic viruses, including PRV and HEV, and suggest the need for active virus surveillance in areas of human and monkey co-habitation to prevent and control emerging zoonotic diseases in the future.

    Matched MeSH terms: Orthoreovirus/classification*; Orthoreovirus/isolation & purification
  11. Leong WJ, Quek XF, Tan HY, Wong KM, Muhammad HS, Mohamed NA, et al.
    J Med Virol, 2022 02;94(2):771-775.
    PMID: 34708881 DOI: 10.1002/jmv.27422
    Pteropine orthoreovirus (PRV) is an emerging zoonotic respiratory virus that can be transmitted from bats to humans. In Malaysia, aside from PRV2P (Pulau virus) being isolated from Pteropus hypomelanus sampled in Tioman Island, PRV3M (Melaka virus), PRV4K (Kampar virus), and PRV7S (Sikamat virus) were all isolated from samples of patients who reported having a disease spectrum from acute respiratory distress to influenza-like illness and sometimes even with enteric symptoms such as diarrhea and abdominal pain. Screening of sera collected from human volunteers on Tioman Island in 2001-2002 demonstrated that 12.8% (14/109) were positive for PRV2P and PRV3M. Taking all these together, we aim to investigate the serological prevalence of PRV (including PRV4K and PRV7S) among Tioman Island inhabitants again with the assumption that the seroprevalence rate will remain nearly similar to the above reported if human exposure to bats is still happening in the island. Using sera collected from human volunteers on the same island in 2017, we demonstrated seroprevalence of 17.8% (28/157) against PRV2P and PRV3M, respectively. Seropositivity of 11.4% among Tioman Island inhabitants against PRV4K and PRV7S, respectively, was described in this study. In addition, the seroprevalence of 89.5% (17/19), 73.6% (14/19), 63.0% (12/19), and 73.6% (14/19) against PRV2P, PRV3M, PRV4K, and PRV7S, respectively, were observed among pteropid bats in the island. We revealed that the seroprevalence of PRV among island inhabitants remains nearly similar after nearly two decades, suggesting that potential spill-over events in bat-human interface areas in the Tioman Island. We are unclear whether such spillover was directly from bats to humans, as suspected for the PRV3M human cases, or from an intermediate host(s) yet to be identified. There is a high possibility of the viruses circulating among the bats as demonstrated by high seroprevalence against PRV in the bats.
    Matched MeSH terms: Orthoreovirus/genetics*; Orthoreovirus/physiology*
  12. Chua KB, Voon K, Yu M, Keniscope C, Abdul Rasid K, Wang LF
    PLoS One, 2011;6(10):e25434.
    PMID: 22022394 DOI: 10.1371/journal.pone.0025434
    Bats are increasingly being recognized as important reservoir hosts for a large number of viruses, some of them can be highly virulent when they infect human and livestock animals. Among the new bat zoonotic viruses discovered in recent years, several reoviruses (respiratory enteric orphan viruses) were found to be able to cause acute respiratory infections in humans, which included Melaka and Kampar viruses discovered in Malaysia, all of them belong to the genus Orthoreovirus, family Reoviridae. In this report, we describe the isolation of a highly related virus from an adult patient who suffered acute respiratory illness in Malaysia. Although there was no direct evidence of bat origin, epidemiological study indicated the potential exposure of the patient to bats before the onset of disease. The current study further demonstrates that spillover events of different strains of related orthoreoviruses from bats to humans are occurring on a regular basis, which calls for more intensive and systematic surveillances to fully assess the true public health impact of these newly discovered bat-borne zoonotic reoviruses.
    Matched MeSH terms: Orthoreovirus/genetics; Orthoreovirus/immunology; Orthoreovirus/physiology*
  13. Tan CW, Wittwer K, Lim XF, Uehara A, Mani S, Wang LF, et al.
    Emerg Microbes Infect, 2019;8(1):787-795.
    PMID: 31132935 DOI: 10.1080/22221751.2019.1621668
    Pteropine orthoreoviruses (PRV) are emerging bat-borne viruses with proven zoonotic transmission. We recently demonstrated human exposure to PRV in Singapore, which together with previous reports from Malaysia and Vietnam suggest that human infection of PRV may occur periodically in the region. This raises the question whether bats are the only sources of human infection. In this study, we screened 517 cynomolgus macaques caught in Singapore for evidence of exposure to PRV3M (also known as Melaka virus), which was first isolated from human patients in Melaka, Malaysia. We found that 67 serum samples were PRV3M positive by ELISA and 34 were also positive by virus neutralization assay. To investigate whether monkeys could act as hosts for PRV transmission, we experimentally infected cynomolgus macaques with PRV3M and housed these animals with uninfected monkeys. Although no clinical signs of infection were observed in infected animals, viral RNA was detected in nasal and rectal swabs and all infected macaques seroconverted. Additionally, one of the uninfected animals seroconverted, implying active shedding and transmission of PRV3M. We provide evidence that PRV exposure in the macaque population in Singapore occurs at a relatively high prevalence and this study suggests that cynomolgus macaques may be an intermediate or reservoir host for PRVs.
    Matched MeSH terms: Orthoreovirus
  14. Tan YF, Teng CL, Chua KB, Voon K
    J Infect Dev Ctries, 2017 Mar 31;11(3):215-219.
    PMID: 28368854 DOI: 10.3855/jidc.9112
    INTRODUCTION: Pteropine orthoreovirus (PRV) is an emerging zoonotic respiratory virus that has spilled over from bats to humans. Though initially found only in bats, further case studies have found viable virus in ill patients.

    METHODOLOGY: PubMed was queried with the keywords of Nelson Bay orthoreovirus OR Pteropine orthoreovirus OR Melaka orthoreovirus OR Kampar orthoreovirus, and returned 17 hits.

    RESULTS: Based on prevalence studies, the presence of PRV has been reported in Malaysia and Vietnam, both developing countries. Other case reports also provide further evidence of the presence of PRV in the Southeast Asian region. Despite the absence of PRV in their home countries, travellers from Hong Kong and Japan to Indonesia have returned to their countries ill with this virus, indicating that local communities in Indonesia might be affected by this virus.

    CONCLUSIONS: This work aims to bring to light this emerging zoonotic respiratory virus circulating among developing countries in Southeast Asia. To improve the understanding of PRV of the medical and scientific community in the Southeast Asian region, this work introduces the general features of PRV, reports of imported PRV, prevalence, and clinical features of PRV. Gaps in knowledge about PRV have also been identified in this work, and we hope that future studies can be undertaken to improve our understanding of this virus.

    Matched MeSH terms: Orthoreovirus/isolation & purification*
  15. Irving AT, Zhang Q, Kong PS, Luko K, Rozario P, Wen M, et al.
    Cell Rep, 2020 11 03;33(5):108345.
    PMID: 33147460 DOI: 10.1016/j.celrep.2020.108345
    Bat cells and tissue have elevated basal expression levels of antiviral genes commonly associated with interferon alpha (IFNα) signaling. Here, we show Interferon Regulatory Factor 1 (IRF1), 3, and 7 levels are elevated in most bat tissues and that, basally, IRFs contribute to the expression of type I IFN ligands and high expression of interferon regulated genes (IRGs). CRISPR knockout (KO) of IRF 1/3/7 in cells reveals distinct subsets of genes affected by each IRF in an IFN-ligand signaling-dependent and largely independent manner. As the master regulators of innate immunity, the IRFs control the kinetics and maintenance of the IRG response and play essential roles in response to influenza A virus (IAV), herpes simplex virus 1 (HSV-1), Melaka virus/Pteropine orthoreovirus 3 Melaka (PRV3M), and Middle East respiratory syndrome-related coronavirus (MERS-CoV) infection. With its differential expression in bats compared to that in humans, this highlights a critical role for basal IRF expression in viral responses and potentially immune cell development in bats with relevance for IRF function in human biology.
    Matched MeSH terms: Orthoreovirus/immunology
  16. Voon K, Tan YF, Leong PP, Teng CL, Gunnasekaran R, Ujang K, et al.
    J Med Virol, 2015 Dec;87(12):2149-53.
    PMID: 26106066 DOI: 10.1002/jmv.24304
    This study aims to assess the incidence rate of Pteropine orthreovirus (PRV) infection in patients with acute upper respiratory tract infection (URTI) in a suburban setting in Malaysia, where bats are known to be present in the neighborhood. Using molecular detection of PRVs directly from oropharyngeal swabs, our study demonstrates that PRV is among one of the common causative agents of acute URTI with cough and sore throat as the commonest presenting clinical features. Phylogenetic analysis on partial major outer and inner capsid proteins shows that these PRV strains are closely related to Melaka and Kampar viruses previously isolated in Malaysia. Further study is required to determine the public health significance of PRV infection in Southeast Asia, especially in cases where co-infection with other pathogens may potentially lead to different clinical outcomes.
    Matched MeSH terms: Orthoreovirus/isolation & purification*
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