• 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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    • 제45권3호
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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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    • 제48권8호
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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]

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

  • 송기준;강병철;이영은;백락주;이용주;송진원
    • 대한바이러스학회지
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    • 제29권2호
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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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국내에서 분리한 닭 레오바이러스의 성상에 관한 연구 (Studies on Properties of Avian Reovirus Isolated in Korea)

  • 김성식;박병옥;김순재
    • 한국동물위생학회지
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    • 제15권1호
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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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한국인 및 가축(돼지)에 있어 Reovirus에 대한 HI 항체분석 (A Study of the HI Antibody of the Koreans and Swine to Reovirus)

  • 이연태;이종훈
    • 대한미생물학회지
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    • 제15권1호
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    • pp.77-84
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    • 1980
  • 본 연구는 한국인 및 한국 각지의 가축에 대한 reovirus 2형의 혈구응집저지항체의 분포를 알어보고저 실시된 연구이다. 사람의 피검물은 1979년 6월부터 12월까지 시내 종합병원에 래원한 신검대상자 총 614명과 한국각지의 가축(돼지) 총 877수를 대상으로 하였다. 돼지의 혈액은 1977년 6월부터 동년 9월까지 전국 25개 지역에서 채취했다. 이들에 대한 혈청을 분리하여 $-20^{\circ}C$에 보관하면서 실험하였고, 혈구응집저지시험은 Rosen(1960b, 1974)의 수기를 따랐다. 항원(Reovirus 2형)은 이호왕(1975) 교수로부터 분양받어 본 교실에서 HeLa 세포에 계대하여 혈구응집가를 확인하여 사용했다. 실험 결과는 다음과 같다. 1. 한국인 총 614명의 Reovirus 2형에 대한 10배 이상 HI항체 보유율은 73.29%로서 한국인이 높은 항체를 보유하고 있었다. 그리고 남녀비는 남자(76.47%)가 여자 (65.12%)보다 약간 높은 경향을 보였다. 2. 연령별로 본 한국인의 항체 보유율은 전 연령군에 고루게 분포되어 있었으나 41세에서 50세군이 85.71%로 약간 높았다. 3. 월별 항체보유율은 6월이 93.22%로 높았고, 10월이 47.62%로 낮았다. 4. 한편 한국의 25개 지역의 총 877수의 돼지에 분포된 항체보유율은 61.80%(542수)였다. 이를 도별로 구분한 바 서울이 83.37%로 가장 높았고, 가장 낮은 지역은 충남으로 40%였다. 5. 월별로 검출된 돼지의 항체보유율은 6월(63.21%)부터 9월(72.25%)까지 사이에 점차 증가되어 가는 경향을 보였다. 6. 사람과 돼지에 분포한 HI 항체가는 그림 2와 같이 대부분이 1:20이내에서 1:80이내에 분포하였으며 상호 차가 있었다. 이상의 실험결과를 토대로 볼때 한국자연계에는 Reovirus 2형이 광범하게 분포되어 있음을 알 수 있었으며, 한국인 및 가축(돼지)에 있어서 높은 항체가를 보유하고 있다는 사실을 새로히 알 수 있었다.

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

  • 정재교;정한솔;안응엽;한승환
    • 한국동물위생학회지
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    • 제42권4호
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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.

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

  • 강미선;김승용;이희선
    • 한국동물위생학회지
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    • 제37권3호
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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 $1,469{\pm}1,230$.

세포배양 유래 생물의약품 제조공정에서 Reovirus, Bovine Viral Diarrhea Virus, Bovine Parainfluenza Virus 동시 검출을 위한 Multiplex Reverse Transcription-PCR (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)

  • 오선환;배정은;김인섭
    • 한국미생물·생명공학회지
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    • 제40권4호
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    • pp.339-347
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    • 2012
  • 동물세포배양 유래 생물의약품 생산 공정에서 다양한 외래성 바이러스가 오염된 사례가 있기 때문에 바이러스 안전성 보증을 위한 바이러스 검출시험이 필수적이다. Reovirus (Reo), bovine viral diarrhea virus (BVDV), bovine parainfluenza virus (BPIV)는 동물 세포주와 동물 세포 배양 공정에 오염되는 대표적인 RNA 바이러스이다. 세포배양 유래 생물의약품의 안전성을 확보하기 위해, 세포주, 원료물질, 제조공정, 완제품에서 Reo, BVDV, BPIV를 동시에 검출할 수 있는 Multiplex Reverse Transcription (RT)-PCR 시험법을 확립하였다. Reo, BVDV, BPIV에 특이적인 primer를 선별하였으며, multiplex RT-PCR 시험법을 최적화하였다. Reo, BVDV, BPIV를 동시에 검출할 수 있는 multiplex RT-PCR 시험법의 민감도는 각각 $7.76{\times}10^2\;TCID_{50}/ml$, $7.44{\times}10^1\;TCID_{50}/ml$, $6.75{\times}10^1\;TCID_{50}/ml$이었다. 확립된 multiplex RT-PCR을 생물의약품 제조공정 검증에 적용할 수 있는지 확인하기 위하여 인위적으로 각 바이러스를 오염시킨 CHO 세포에서 검출 시험을 실시한 결과 각 바이러스를 감염시킨 CHO 세포와 세포배양 상청액에서 각 바이러스를 검출할 수 있었다. 위와 같은 결과에서 확립된 multiplex RT-PCR시험법은 세포주, 원료물질, 제조공정, 완제품에서 Reo, BVDV, BPIV를 동시에 검출할 수 있는 특이성과 민감성이 우수한 시험법임을 확인하였다.