Viral Profiling Identifies Multiple Subtypes of Kaposi's Sarcoma
Viral Profiling Identifies Multiple Subtypes of Kaposi's Sarcoma
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DOI：
10.1128/mbio.01633-14
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发表时间：
2014-09-01
期刊：
影响因子：
6.4
通讯作者：
Dittmer, Dirk P.
中科院分区：
文献类型：
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作者：
Hosseinipour, Mina C.;Sweet, Kristen M.;Dittmer, Dirk P.
卡波西肉瘤（KS）由KS相关疱疹病毒（KSHV）引起，是当今马拉维和美国HIV感染患者中最常见的癌症。在马拉维，KSHV是地方病。我们对没有化疗或抗逆转录病毒治疗（ART）史的HIV感染和KS患者进行了一项横断面研究。入组了70例患者。81%患有T1（晚期）KS。中位CD 4和HIV RNA水平分别为181个细胞/mm（3）和138，641个拷贝/ml。我们有完整的信息和合适的血浆和活检样本66例。对于59/66例（89%）患者，在血浆中发现可检测的KSHV载量（中位数，2，291拷贝/ml;四分位数范围[IQR]，741至5，623）。我们利用一种新的KSHV实时定量PCR（qPCR）阵列，每个开放阅读框具有多个引物，以检查KSHV转录。17个样品仅显示出最低水平的KSHV mRNA，可能是由于受感染细胞的数量有限。对于所有其他活检样本，病毒潜伏基因座（拉娜、vCyc、vFLIP、卡泊辛和microRNA [miRNA]）大量转录，K15 mRNA也是如此。我们可以确定两种亚型的治疗初治KS：病变的转录病毒RNA的整个长度的病毒基因组和病变，仅显示有限的转录限制在潜伏位点。这一发现首次证明了在HIV和KS治疗初治患者中存在多种亚型的KS病变。重要性KS是全球HIV感染者中的主要癌症，与KSHV感染有因果关系。使用病毒转录谱，我们已经证明了存在的KS病变的多个亚型的首次在HIV和KS治疗初治患者。大量的病变转录编码病毒激酶的mRNA，因此除了化疗之外，抗病毒药物更昔洛韦或AZT也可以靶向这些病变。
Kaposi's sarcoma (KS), caused by KS-associated herpesvirus (KSHV), is the most common cancer among HIV-infected patients in Malawi and in the United States today. In Malawi, KSHV is endemic. We conducted a cross-sectional study of patients with HIV infection and KS with no history of chemo-or antiretroviral therapy (ART). Seventy patients were enrolled. Eighty-one percent had T1 (advanced) KS. Median CD4 and HIV RNA levels were 181 cells/mm(3) and 138,641 copies/ml, respectively. We had complete information and suitable plasma and biopsy samples for 66 patients. For 59/66 (89%) patients, a detectable KSHV load was found in plasma (median, 2,291 copies/ml; interquartile range [IQR], 741 to 5,623). We utilized a novel KSHV real-time quantitative PCR (qPCR) array with multiple primers per open reading frame to examine KSHV transcription. Seventeen samples exhibited only minimal levels of KSHV mRNAs, presumably due to the limited number of infected cells. For all other biopsy samples, the viral latency locus (LANA, vCyc, vFLIP, kaposin, and microRNAs [miRNAs]) was transcribed abundantly, as was K15 mRNA. We could identify two subtypes of treatment-naive KS: lesions that transcribed viral RNAs across the length of the viral genome and lesions that displayed only limited transcription restricted to the latency locus. This finding demonstrates for the first time the existence of multiple subtypes of KS lesions in HIV- and KS-treatment naive patients.IMPORTANCE KS is the leading cancer in people infected with HIV worldwide and is causally linked to KSHV infection. Using viral transcription profiling, we have demonstrated the existence of multiple subtypes of KS lesions for the first time in HIV-and KS-treatment-naive patients. A substantial number of lesions transcribe mRNAs which encode the viral kinases and hence could be targeted by the antiviral drugs ganciclovir or AZT in addition to chemotherapy.