Macaque homologs of EBV and KSHV show uniquely different associations with simian AIDS-related lymphomas.
Macaque homologs of EBV and KSHV show uniquely different associations with simian AIDS-related lymphomas.
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DOI：
10.1371/journal.ppat.1002962
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发表时间：
2012
期刊：
影响因子：
6.7
通讯作者：
Rose TM
中科院分区：
文献类型：
--
作者：
Bruce AG;Bielefeldt-Ohmann H;Barcy S;Bakke AM;Lewis P;Tsai CC;Murnane RD;Rose TM
两种γ-疱疹病毒，爱泼斯坦 - 巴尔病毒（EBV）（淋巴隐病毒属）和卡波西肉瘤相关疱疹病毒（KSHV）（拉迪诺病毒属）与艾滋病相关淋巴瘤的病因有关。在猕猴和其他非人灵长类动物中已发现这些病毒的同源物。为了评估这些病毒与非人灵长类动物疾病的关联，对存档的淋巴瘤样本进行了筛选，以检测EBV的猕猴淋巴隐病毒（LCV）同源物以及属于KSHV同源物的RV1谱系或旧大陆灵长类拉迪诺病毒更遥远的RV2谱系的猕猴拉迪诺病毒的存在。通过定量聚合酶链反应（QPCR）确定病毒载量，并通过对不同病毒蛋白进行免疫标记来识别感染细胞。淋巴瘤分为三组。第一组（n = 6）与猴免疫缺陷病毒/猴人免疫缺陷病毒（SIV/SHIV）感染有关，含有高水平的LCV（1 - 25个基因组/细胞），并表达B细胞抗原CD20或BLA.36。在其中一个LCV高水平的淋巴瘤的肿瘤细胞核中检测到强烈的EBNA - 2信号，表明处于III型潜伏期。该组淋巴瘤均未对LCV病毒衣壳抗原（VCA）裂解标志物染色。第二组（n = 5）与D型猴逆转录病毒 - 2（SRV - 2）感染有关，含有高水平的RV2拉迪诺病毒（9 - 790个基因组/细胞），并表达CD3 T细胞标志物。第三组（n = 3）与SIV/SHIV感染有关，含有高水平的RV2拉迪诺病毒（2 - 260个基因组/细胞），且CD20和CD3均为阴性。在CD3阳性和CD3/CD20阴性的淋巴瘤中，肿瘤细胞对RV2裂解复制标志物染色强烈。所有淋巴瘤中均未检测到腹膜后纤维瘤病疱疹病毒（RFHV），即KSHV的猕猴RV1同源物的水平。我们的数据表明淋巴隐病毒和RV2拉迪诺病毒在猴艾滋病相关淋巴瘤的发展中都具有病因学作用，并表明病毒感染的肿瘤性淋巴细胞来自不同的淋巴细胞谱系和分化阶段。
卡波西肉瘤（KS）和非霍奇金淋巴瘤的发病率随着艾滋病病毒疾病和艾滋病的流行而增加。现在已知这些恶性肿瘤与γ - 疱疹病毒的继发感染有关；卡波西肉瘤与卡波西肉瘤相关疱疹病毒（KSHV）有关，淋巴瘤与KSHV和爱泼斯坦 - 巴尔病毒（EBV）都有关。在患有猴艾滋病的猴子中观察到了类似的艾滋病相关恶性肿瘤，并且与KSHV和EBV相关的猴γ - 疱疹病毒与疾病的发展有关。对艾滋病相关恶性肿瘤的猴模型的研究为理解γ - 疱疹病毒在艾滋病相关肿瘤发生中的作用提供了重要方法。在这里，我们使用了分子和免疫学相结合的方法来识别、定量和定位猕猴艾滋病相关淋巴瘤中γ - 疱疹病毒的感染。我们在不同类型的猕猴淋巴瘤的肿瘤细胞中发现了高水平的与EBV和KSHV相关的猕猴病毒，这表明病毒感染的肿瘤细胞属于不同的淋巴细胞谱系和分化阶段。
Two gammaherpesviruses, Epstein-Barr virus (EBV) (Lymphocryptovirus genus) and Kaposi's sarcoma-associated herpesvirus (KSHV) (Rhadinovirus genus) have been implicated in the etiology of AIDS-associated lymphomas. Homologs of these viruses have been identified in macaques and other non-human primates. In order to assess the association of these viruses with non-human primate disease, archived lymphoma samples were screened for the presence of macaque lymphocryptovirus (LCV) homologs of EBV, and macaque rhadinoviruses belonging to the RV1 lineage of KSHV homologs or the more distant RV2 lineage of Old World primate rhadinoviruses. Viral loads were determined by QPCR and infected cells were identified by immunolabeling for different viral proteins. The lymphomas segregated into three groups. The first group (n = 6) was associated with SIV/SHIV infections, contained high levels of LCV (1–25 genomes/cell) and expressed the B-cell antigens CD20 or BLA.36. A strong EBNA-2 signal was detected in the nuclei of the neoplastic cells in one of the LCV-high lymphomas, indicative of a type III latency stage. None of the lymphomas in this group stained for the LCV viral capsid antigen (VCA) lytic marker. The second group (n = 5) was associated with D-type simian retrovirus-2 (SRV-2) infections, contained high levels of RV2 rhadinovirus (9–790 genomes/cell) and expressed the CD3 T-cell marker. The third group (n = 3) was associated with SIV/SHIV infections, contained high levels of RV2 rhadinovirus (2–260 genomes/cell) and was negative for both CD20 and CD3. In both the CD3-positive and CD3/CD20-negative lymphomas, the neoplastic cells stained strongly for markers of RV2 lytic replication. None of the lymphomas had detectable levels of retroperitoneal fibromatosis herpesvirus (RFHV), the macaque RV1 homolog of KSHV. Our data suggest etiological roles for both lymphocryptoviruses and RV2 rhadinoviruses in the development of simian AIDS-associated lymphomas and indicate that the virus-infected neoplastic lymphoid cells are derived from different lymphocyte lineages and differentiation stages. The incidence of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma increased in conjunction with the epidemic of HIV disease and AIDS. These malignancies are now known to be associated with secondary infections with a gammaherpesvirus; KS, with the Kaposi's sarcoma-associated herpesvirus (KSHV) and lymphoma, with both KSHV and Epstein-Barr virus (EBV). Similar AIDS-related malignancies have been observed in monkeys with simian AIDS and monkey gammaherpesviruses related to KSHV and EBV have been implicated in the development of disease. The study of monkey models of AIDS-related malignancies provides important approaches for understanding the role of gammaherpesviruses in AIDS-related tumorigenesis. Here we have used a combined molecular and immunological approach to identify, quantitate and localize infections of gammaherpesviruses in AIDS-associated lymphomas in macaques. We found high levels of macaque viruses related to EBV and KSHV in the tumor cells of distinct types of macaque lymphomas, suggesting that the virus-infected tumor cells belong to different lymphocyte lineages and differentiation stages.
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影响因子：
2.4
作者：
Bielefeldt-Ohmann, H;Barouch, DH;Rose, TM
通讯作者：
Rose, TM
影响因子：
4.8
作者：
Bruce, A. Gregory;Bakke, Angela M.;Rose, Timothy M.
通讯作者：
Rose, Timothy M.
影响因子：
5.4
作者：
Greensill, J;Sheldon, JA;Schulz, TF
通讯作者：
Schulz, TF
影响因子：
6.4
作者：
LI, SL;BIBERFELD, P;ERNBERG, I
通讯作者：
ERNBERG, I
影响因子：
6.4
作者：
LI, SL;FEICHTINGER, H;ERNBERG, I
通讯作者：
ERNBERG, I