• Title/Summary/Keyword: Reovirus

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Reovirus and Tumor Oncolysis

  • Kim, Man-Bok;Chung, Young-Hwa;Johnston, Randal N.
    • Journal of Microbiology
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    • v.45 no.3
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    • pp.187-192
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    • 2007
  • REOviruses (Respiratory Enteric Orphan viruses) are ubiquitous, non-enveloped viruses containing 10 segments of double-stranded RNA (dsRNA) as their genome. They are common isolates of the respiratory and gastrointestinal tract of humans but are not associated with severe disease and are therefore considered relatively benign. An intriguing characteristic of reovirus is its innate oncolytic potential, which is linked to the transformed state of the cell. When immortalized cells are transfected in vitro with activated oncogenes such as Ras, Sos, v-erbB, or c-myc, they became susceptible to reovirus infection and subsequent cellular lysis, indicating that oncogene signaling pathways are exploited by reovirus. This observation has led to the use of the virus in clinical trials as an anti-cancer agent against oncogenic tumors. In addition to the exploitation of oncogene signaling, reovirus may further utilize host immune responses to enhance its antitumor activity in vivo due to its innate interferon induction ability. Reovirus is, however, not entirely benign to immunocompromised animal models. Reovirus causes so-called "black feet syndrome" in immunodeficient mice and can also harm neonatal animals. Because cancer patients often undergo immunosuppression due to heavy chemo/radiation-treatments or advanced tumor progression, this pathogenic response may be a hurdle in virus-based anticancer therapies. However, a genetically attenuated reovirus variant derived from persistent reovirus infection of cells in vitro is able to exert potent anti-tumor activity with significantly reduced viral pathogenesis in immunocompromised animals. Importantly, in this instance the attenuated, reovirus maintains its oncolytic potential while significantly reducing viral pathogenesis in vivo.

Naturally occurring reoviruses for human cancer therapy

  • Kim, Manbok
    • BMB Reports
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    • v.48 no.8
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    • pp.454-460
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    • 2015
  • Naturally occurring reoviruses are live replication-proficient viruses that specifically infect human cancer cells while sparing their normal counterpart. Since the discovery of reoviruses in 1950s, they have shown various degrees of safety and efficacy in pre-clinical or clinical applications for human anti-cancer therapeutics. I have recently discovered that cellular tumor suppressor genes are also important in determining reoviral tropism. Carcinogenesis is a multi-step process involving the accumulation of both oncogene and tumor suppressor gene abnormalities. Reoviruses can exploit abnormal cellular tumor suppressor signaling for their oncolytic specificity and efficacy. Many tumor suppressor genes such as p53, ataxia telangiectasia mutated (ATM), and retinoblastoma associated (RB) are known to play important roles in genomic fidelity/maintenance. Thus, a tumor suppressor gene abnormality could affect host genomic integrity and likely disrupt intact antiviral networks due to the accumulation of genetic defects which in turn could result in oncolytic reovirus susceptibility. This review outlines the discovery of oncolytic reovirus strains, recent progresses in elucidating the molecular connection between oncogene/tumor suppressor gene abnormalities and reoviral oncotropism, and their clinical implications. Future directions in the utility of reovirus virotherapy is also proposed in this review. [BMB Reports 2015; 48(8): 454-460]

Isolation and Characterization of Reovirus in Korea (한국에 분포하는 레오바이러스의 분리 및 동정)

  • Song, Ki-Joon;Kang, Byung-Chul;Lee, Young-Eun;Baek, Luck-Ju;Lee, Yong-Ju;Song, Jin-Won
    • The Journal of Korean Society of Virology
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    • v.29 no.2
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    • pp.65-74
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    • 1999
  • Reovirus was found to inhabit both the respiratory and the enteric tract of human and animals. The genome of reovirus comprises 10 segments of double-stranded RNA, total size 24 kbp. Nine strains of reovirus were isolated from human and field mice in Korea. Aseptically collected sera from human and lung tissues from field mice were used for virus isolation. For serotype determination, hemagglutination inhibition test was used, and three strains were confirmed to type 2 and six strains to type 3. To determine the genomic diversity and molecular phylogeny of reoviruses isolated in Korea, part of S4 genomic segment of reovirus was enzymatically amplified and directly sequenced. In nucleotide level, Apo98-35 strain showed 15.4%, 19.3%, and 14.4% differences compared to type 1 (T1L, Lang), type 2 (T2J), and type 3 reference strains, respectively. In amino acid level, Apo98-35 strain showed 10.5%, 13.7%, and 9.5% differences compared to type 1, type 2, and type 3 reference strains, respectively. Using the maximum parsimony method based on 285 bp spaning region of the S4 genomic segment, phylogenetic analysis indicated that Apo98-35 from Korea formed different phylogenetic branch. Our data obtained by sequence and phylogenetic analyses of reoviruses are consistent with the distinct geographically dependent evolution of reoviruses in Korea.

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Studies on Properties of Avian Reovirus Isolated in Korea (국내에서 분리한 닭 레오바이러스의 성상에 관한 연구)

  • 김성식;박병옥;김순재
    • Korean Journal of Veterinary Service
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    • v.15 no.1
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    • pp.67-80
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    • 1992
  • Avian reoviruses have been implicated in respiratory disease enteric conditions including Cloacal pasting in young thicks, pericarditis, hydropericardium, anaemia with swollen spleen and liver and petechiation of skeletal muscle and viral arthritis. This study was conducted to examine properties of reovirus field 3 strains isolated from affected broiler from several farms. An infectious agent was isolated from leg tendons and intestine of broiler with clinical tenosynovitis. The agent grew well on the chicken embryo kideny cells(CEK). One of them produced cytopathic effects(CPE) of round type and formed intranuclear inclusions, and the other was characterized by CPE of syncytical type and cytoplasmic inclusion. The properties and serological classification of field strains were examined by hemagglutin test, virus neutralization test, agar gel precipitin, electropherotype. They showed no hemagglutination reactions and not well neutralization and to possess common antigens detectable by AGP test. RNA electropherotype presented 10 segment band as the previous report. These data suggest that the field strains and standard strains (1133, 1733) may be the same group.

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A Study of the HI Antibody of the Koreans and Swine to Reovirus (한국인 및 가축(돼지)에 있어 Reovirus에 대한 HI 항체분석)

  • Lee, Yun-Tai;Lee, Chong-Hoon
    • The Journal of the Korean Society for Microbiology
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    • v.15 no.1
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    • pp.77-84
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    • 1980
  • The purpose of this paper is to study the incidence of humoral antibody to reovirus type 2 in the sera of the Koreans and animal(swine) at random. All the 614 of human beings and 877 of swine sera were collected during the period from June to December, 1979, from the healthy persons in the National Seoul Hospital and swine blood was collected from 25 different areas of June to 30th of September in 1977. The HI test was put with plastic plates according to the methods by Rosen(1960 a and 1974). The total 73.29% of the 614 cases in human and the 61.80% of the 877 in swine confirmed as a hemagglutination inhibition antibodies. In human the 76.47% of the 442 male cases and the 65.12% of the 172 female ones were confirmed to have humoral antibodies. The positive rate was widely shown in each age group. But the 31 to 50 old age groups showed a little higher than any other age group, which came to the 85.71% in 41-50 and the 78.72% in 31-40 old age groups. The monthly distribution of HI antibody was shown to reach the 93.22% of the 59 cases in June. This per cent was much higher than of any other distribution. Accordingly, the auther came to the conclusion that there is reovirus type 2 in all the parts of Korea and most of the Koreans have the higher rates of antibody. However, the positive rate of antibody was the 542 out of the 877 cases(61.8%) from the swine and antibodies was confirmed from the 25 different areas in Korea. The seasonal distribution of the antibody showed these high rates. In domestics animals; blood from the swine showed that distribution of HI antibodies to reoviras type 2. These antibody appears from the various areas of the province in Korea. For this reasons, reovirus was widely distributed in this country.

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The prevalence of avian reovirus infection in poultry farms of Jeonbuk province, Korea (전북지역 양계농가의 조류레오바이러스 유병율 조사)

  • Jeong, Jae-Kyo;Jeong, Hansol;An, Euingyoub;Han, Seunghwan
    • Korean Journal of Veterinary Service
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    • v.42 no.4
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    • pp.237-243
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    • 2019
  • Avian reovirus (ARV) is the pathogenic agent of tenosynovitis and malabsorption syndrome in broiler, which has caused significant economical losses due to poor feeder efficiency and stunting. In order to determine the prevalence of ARV infection in poultry farms in Jeonbuk province, Korea, we performed a surveillance study by testing 179 cecal samples from 131 broiler farms for virus detection, and 1,181 serum samples from 33 broiler farms (n=292) and 22 broiler breeder farms (n=1,525) for antibody detection in the province. Virological examination using RT-PCR showed that ARV were detected in 26.0% of the tested farms (34/131),with the highest positive rates in broilers of 6 days old or more in summer season. In serological test using ELISA, broiler and broiler breeder farms examined were all ARV antibody positive. In broiler, the positive rate and antibody titers showed a tendency to decrease with age in contrast to those of broiler breeders. Our results indicate that ARV is ubiquitous in broilers and broiler breeders in the province.

Seroprevalence of Metapneumovirus, Reovirus and Mycoplasma in the broiler breeder of Jeonbuk province (전북지역 종계에서 Metapneumovirus, Reovirus, Mycoplasma 항체가 조사)

  • Kang, Mi-Seon;Kim, Seung-Yong;Lee, Hee-Seon
    • Korean Journal of Veterinary Service
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    • v.37 no.3
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    • pp.185-190
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    • 2014
  • We investigated the serological prevalence of avian metapneumovirus (AMPV), avian reovirus (ARV), Mycoplasma gallisepticum (MG) and Mycoplasma synoviae (MS) in 760 broiler breeder (38 flocks), in the Jeonbuk province in 2013. This study was conducted to evaluate the immune and infection status of the broiler breeder flocks against AMPV, ARV, MG, MS by an enzyme-linked immunosorbent assay (ELISA). Serological test for AMPV were positive 37 (97.3%) flocks and 712 (93.6%) broiler breeder and geometric mean antibody titers were $16,350{\pm}10,195$, ARV were high positive rate 100% (38/38) flocks and 97.8% (743/760). The seropositive flocks against MG were 71.1% (27/38) and the geometric mean antibody titers were $2,474{\pm}2,045$, whereas the rates of positive flocks against MS were 50.0% (19/38) and the geometric mean antibody titers were $1,469{\pm}1,230$.

Multiplex Reverse Transcription-PCR for Simultaneous Detection of Reovirus, Bovine Viral Diarrhea Virus, and Bovine Parainfluenza Virus during the Manufacture of Cell Culture-derived Biopharmaceuticals (세포배양 유래 생물의약품 제조공정에서 Reovirus, Bovine Viral Diarrhea Virus, Bovine Parainfluenza Virus 동시 검출을 위한 Multiplex Reverse Transcription-PCR)

  • Oh, Seon Hwan;Bae, Jung Eun;Kim, In Seop
    • Microbiology and Biotechnology Letters
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    • v.40 no.4
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    • pp.339-347
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    • 2012
  • Viral safety is an important prerequisite for clinical preparations of mammalian cell culture-derived biopharmaceuticals, because numerous adventitious viruses have been contaminated during the manufacturing process. In particular, Chinese hamster ovary (CHO) cells are highly susceptible to several RNA viruses including reovirus (Reo), bovine viral diarrhea virus (BVDV), and bovine parainfluenza virus (BPIV) and there have been reports of such viral contaminations. Therefore, viral detection during the CHO cell process is necessary to ensure the safety of biopharmaceuticals against viruses. In this study, a multiplex reverse transcription (RT)-PCR assay was developed and subsequently evaluated for its effectiveness as a means to simultaneously detect Reo, BVDV, and BPIV during the manufacture of cell culture-derived biopharmaceuticals. Specific primers for Reo, BVDV, and BPIV were selected, and a multiplex RT-PCR was optimized. The sensitivity of the assay for simultaneous amplification of all viral target RNAs was $7.76{\times}10^2\;TCID_{50}/ml$ for Reo, $7.44{\times}10^1\;TCID_{50}/ml$ for BVDV, and $6.75{\times}10^1\;TCID_{50}/ml$ for BPIV. The multiplex RT-PCR was proven to be very specific to Reo, BVDV, and BPIV and was subsequently applied to the validation of CHO cells artificially infected with each virus. It could detect each viral RNA from CHO cells as well as culture supernatants. Therefore, it was concluded that the multiplex RT-PCR assay can be applied to detection of the adventitious viruses during the manufacture of cell culture-derived biopharmaceuticals.