Epstein-Barr virus DNA is detected in peripheral blood mononuclear cells of EBV-seronegative infants with infectious mononucleosis-like symptoms.
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Mononucleosis
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Abstract A concentration of disodium phosphonoacetate (PA) has been defined which will reduce the synthesis of infectious EB virus in a producer cell line to 1% of control values but which will not affect the growth of EB virus‐transformed cells in a 12‐week colony‐forming assay. When total mononuclear cells or T‐lymphocyte‐depleted mononuclear cells from the blood of acute IM patients were cultured in the presence of PA at the above concentration, the regular establishment of EB virus genome‐containing cell lines seen in control cultures was almost totally abolished. In further experiments, when T‐lymphocyte‐depleted IM mononuclear cells were co‐cultivated with foetal cells of the opposite sex in the presence and absence of PA, cell lines of mixed or of exclusively foetal origin were obtained not only from control co‐cultures but also on those rare occasions when transformed foci developed in PA‐treated co‐cultures. The results suggest that all cell lines derived from the blood of IM patients are initiated in culture by a two‐step process of virus release and secondary infection, and argue against the occurrence of any direct outgrowth of IM cells transformed by the virus in vivo .
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The quantitative analysis of the cells infected with Epstein-Barr virus was performed on the peripheral blood mononuclear cells from the patients with infectious mononucleosis, by using in situ hybridization with Epstein-Barr virus encoded small nuclear RNA1 (EBER1). An alkaline-phosphatase conjugated oligonucleotide probe complementary to EBER1 was used as an antisense probe, while oligonucleotide DNA probe compatible with the sequence of EBER1 was used as a sense probe, control probe. The EBER1 positive cells on the slide-glass were enumerated microscopically. In situ hybridization revealed that 50,000 peripheral blood mononuclear cells from the patients in the acute phase of infectious mononucleosis contained 35 +/- 36 cells infected with Epstein-Barr virus (n = 11). The cells infected with Epstein-Barr virus apparently decreased in the convalescence of all the patients with infectious mononucleosis and the mean of the cells infected with Epstein-Barr virus was 3 +/- 4 in the convalescence (n = 6) (p < 0.02). On the other hand, no positive cells were detected in healthy individuals with past-infection of Epstein-Barr virus (n = 10) or without any previous Epstein-Barr virus infection (n = 11). The striking increase of the cells with Epstein-Barr virus genome was clearly demonstrated in the peripheral blood mononuclear cells from the patients with infectious mononucleosis.
Mononucleosis
Convalescence
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Three strains of Epstein-Barr virus (EBV), two from Burkitt lymphoma (BL) and one from infectious mononucleosis (IM) were used to transform separate cultures of the same batch of primary marmoset leukocytes, and the viruses released from the transformants were compared. The three viruses shared properties of the transforming biotype of EBV, namely, stimulation of DNA synthesis and immortalization of cord blood leukocytes, and failure to induce "early antigen" in lymphoblast lines. All viruses produced more virus in transformed marmoset cells than in transformed human cells, as measured by the number of EBV genomes detected by complementary RNA/DNA hybridization, by virus capsid antigen expression, or by released virions and biologically active virus. Reference human sera and sera from primary EBV infections were used to compare the three virus strains in a virus neutralization test based on inhibition of stimulation of DNA synthesis. Specimens taken late in convalescence from patients with mononucleosis and sera from marmosets experimentally infected with virus from a patient with mononucleosis neutralized the homologous virus, as well as the two virus strains isolated from patients with BL. This finding indicates that viral antigens that elicit neutralizing antibodies are shared among the strains. However, in certain sera the neutralizing-antibody titer against one strain was consistently higher than against another strain. Furthermore, sera taken early after onset of IM contained low levels of neutralizing antibody against IM-derived virus, but failed to neutralize BL-derived virus. These latter findings suggest the existence of heterogeneity among surface antigens of EBVs. The results emphasize the biological and antigenic similarity of EBV isolates from BL and IM and do not suggest major subtype variations. It remains to be determined whether antigenic diversity such as described or virus genome variation detectable by other means is epidemiologically significant.
Mononucleosis
Antibody-dependent enhancement
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The potential involvement of Epstein-Barr virus (EBV) in AIDS was examined by determining the type of EBV-specific antibody responses and the EBV content or lymphoproliferative ability present in selected body fluids of patients with AIDS or AIDS-related complex. The results were compared with two control groups. An enhanced antibody response to a broad spectrum of EBV antigens was found in patients with AIDS or AIDS-related complex. The pattern of virus-specific antibody responses resembled that associated with a persistent or reactivated infection. The content of EBV in oropharyngeal secretions and the lymphoproliferative ability in peripheral blood from patients with AIDS or AIDSrelated complex was significantly greater than that from healthy controls and approached levels detected in the control group with infectious mononucleosis. These findings, together with recent reports of cellular-level interaction between EBV and human T lymphotropic virus type III, suggest that EBV may have a contributory role in these disorders.
Mononucleosis
Lymphoproliferative Disorders
AIDS-related complex
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Inhibition of mTORC1 inhibits lytic replication of Epstein-Barr virus in a cell-type specific manner
Epstein-Barr virus is a human herpesvirus that infects a majority of the human population. Primary infection of Epstein-Barr virus (EBV) causes the syndrome infectious mononucleosis. This virus is also associated with several cancers, including Burkitt's lymphoma, post-transplant lymphoproliferative disorder and nasopharyngeal carcinoma. As all herpesvirus family members, EBV initially replicates lytically to produce abundant virus particles, then enters a latent state to remain within the host indefinitely. Through a genetic screen in Drosophila, we determined that reduction of Drosophila Tor activity altered EBV immediate-early protein function. To further investigate this finding, we inhibited mTOR in EBV-positive cells and investigated subsequent changes to lytic replication via Western blotting, flow cytometry, and quantitative PCR. The student T-test was used to evaluate significance. mTOR, the human homolog of Drosophila Tor, is an important protein at the center of a major signaling pathway that controls many aspects of cell biology. As the EBV immediate-early genes are responsible for EBV lytic replication, we examined the effect of inhibition of mTORC1 on EBV lytic replication in human EBV-positive cell lines. We determined that treatment of cells with rapamycin, which is an inhibitor of mTORC1 activity, led to a reduction in the ability of B cell lines to undergo lytic replication. In contrast, EBV-positive epithelial cell lines underwent higher levels of lytic replication when treated with rapamycin. Overall, the responses of EBV-positive cell lines vary when treated with mTOR inhibitors, and this may be important when considering such inhibitors as anti-cancer therapeutic agents.
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More than 200 cells were cloned from populations of mammalian cells persistently infected with Japanese encephalitis virus. Only four cloned cultures contained cells that had viral antigen measurable by immunofluorescence and that released infectious virus, yet all clones harbored virus-specific RNA. Superinfection of cloned cells with wild-type Japanese encephalitis virus did not produce cytopathic effects, but resulted in production of viral antigen and infectious virus in formerly nonproducing clones. Cocultivation of nonproducer clone cells with normally permissive cells did not induce virus production, nor did treatment of nonproducer clones with various inhibitors of DNA, RNA, or protein synthesis. It is suggested that the cloning procedure may have selected for a particular subpopulation of cells and that defective virus is also involved in establishment and maintenance of persistent infection.
clone (Java method)
Viral transformation
Superinfection
Viral Interference
Helper virus
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Abstract A strong association exists between Epstein‐Barr (EB) virus and two human cancers, endemic Burkitt's lymphoma and nasopharyngeal carcinoma. In addition, the virus causes infectious mononucleosis [reviewed in Epstein and Achong, 1979, 1986] and more recently has been implicated in lymphomas arising in immunosuppressed individuals [Cleary et al., 1986]. The possibility of preventing or influencing the course of these diseases by vaccination has been advocated for a number of years [Epstein, 1976]. especially in the case of undifferentiated nasopharyngeal carcinoma, which is the most common tumour of men in southern China and is prevalent in other specific regions; it therefore represents a major world cancer problem [Shanmugaratnam, 1971]. Two vaccinia virus strains were employed to make recombinants expressing the gene coding for the EB virus envelope glycoprotein, gp340, and were used to vaccinate cottontop tamarins. Protection against EB‐virus‐induced lymphoma was obtained in animals immunized with the laboratory (WR) strain recombinant but not with those recombinants derived from the vaccine (Wyeth) strain. Circulating antibodies to EB virus gp340 were not detected in any of the immunized animals.
Orthopoxvirus
Mononucleosis
Poxviridae
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서론: 엡스타인-바 바이러스(Epstein-Barr virus, EBV)는 human herpes viridae에 속하는 B lymphotropic virus로 전염성단핵구증(infectious mononucleosis), 위암, 림프종 등을 일으키는 원인으로 알려져 있다. EBV 연관 급성 위염에 대한 보고는 국내에서 한차례 소개된 바 있으나 양성 위궤양으로 발현된 예는 국내에서 현재까지 없고 외국에서도 드물게 보고되고 있다. 저자들은 EBV와 연관되어 발생한 위궤양 환자 1예를 경험하였기에 이를 보고하는 바이다. 증례: 특이병력이 없는 36세 남자가 내원 2주전부터 발생한 명치부위의 속쓰림 및 소화불량을 주소로 본원 소화기내과를 방문하였다. 환자는 내원 한달 전에 기침, 열감 및 오한증상이 있었고 서혜부 림프절이 만져져 비뇨기과 진료를 본적 있었다. 상부위장관내시경을 시행하였고 위 전정부 소만에 삼출물과 응고된 혈액으로 덮여있는 궤양침윤형 병변이 관찰되어 진행성 위암을 배제하기 위해 조직검사를 시행하였다.H&E 염색에서 비정형 림프구들이 관찰되었으나 면역조직화학 염색에서 이들은 CK-AE1/AE3, L26 에 음성을 보였고 EBV에 대한 제자리부합법 검사에서 양성반응을 보여 EBV 연관 점액점막 궤양으로 진단하였다. 프로톤펌프억제제를 사용하면서 추적관찰 중 주 증상과 임파선종대는 소실되었고 6개월 후 시행한 내시경에서 궤양은 반흔으로 치유되어 현재 소화기내과 외래에서 추적관찰 중이다.
Mononucleosis
Gammaherpesvirinae
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Serial sera from 50 marrow transplant recipients were examined for their spectra and titers of antibodies to EBV-specific antigens. Immediately before or after transplant, blood products passively transferred antibodies to EB viral capsid antigen (VCA) and EBV nuclear antigen (EBNA). In most recipients, passively-transferred antibodies were replaced by endogenous antibodies regardless of whether donor or recipient had EBV antibodies before transplantation. Commencement or resumption of endogenous EBV antibody production was not associated with signs of infectious mononucleosis or heterophil antibody responses. Antibodies to VCA rose to abnormally high titers, followed successively by antibody to early antigens (EA), and disproportionately low levels of anti-EBNA. Unusually high anti-VCA and anti-EA levels persisted when tests of immune function returned to normal. Antibodies to other herpes group viruses showed no consistent changes. We conclude that (1) EBV does not cause significant clinical problems in marrow transplant recipients; (2) persistent EBV infection can become established or reestablished in the presence of antibodies to EBV; (3) marrow transplant recipients show the same exaggerated immune response to EBV as other immunodeficient patients; and (4) the pattern of EBV-specific antibodies may be a more sensitive measure of defective cell-mediated immunity than most conventional tests of immune function.
Mononucleosis
Antibody titer
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