Heterogeneity and breadth of host antibody response to KSHV infection demonstrated by systematic analysis of the KSHV proteome.
Heterogeneity and breadth of host antibody response to KSHV infection demonstrated by systematic analysis of the KSHV proteome.
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DOI：
10.1371/journal.ppat.1004046
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发表时间：
2014-03
期刊：
影响因子：
6.7
通讯作者：
Whitby D
中科院分区：
文献类型：
--
作者：
Labo N;Miley W;Marshall V;Gillette W;Esposito D;Bess M;Turano A;Uldrick T;Polizzotto MN;Wyvill KM;Bagni R;Yarchoan R;Whitby D
卡波西肉瘤相关疱疹病毒（KSHV）基因组编码超过85个开放阅读框（ORF）。KSHV感染的血清学评价现在通常依赖于仅对一种潜伏蛋白和/或一种裂解蛋白（通常为ORF 73和K8.1）的反应性。由病毒编码的大多数其他多肽具有未知的抗原谱。我们在重组系统中系统地表达和纯化了来自72个KSHV ORF的产物，并分析了美国KSHV相关恶性肿瘤患者和美国献血者（低KSHV血清阳性率人群）的血清反应性。我们鉴定了几种KSHV蛋白（ORF 38，ORF 61，ORF 59和K5），它们在患有KSHV相关疾病的个体中引起了显著的反应。在这些患者中，反应模式是异质性的;然而，HIV感染似乎与血清学反应的广度和强度相关。另外的ORF的改进的抗原表征可能增加血清学测定的灵敏度，导致更快的进展，在理解KSHV的免疫应答，并允许更好地理解KSHV感染的自然史。为此，我们开发了一种基于珠的多重检测方法，检测六种KSHV抗原的抗体。卡波西肉瘤相关疱疹病毒（KSHV）是卡波西肉瘤、原发性渗出性淋巴瘤和多中心Castleman病的一种形式的原因，主要影响HIV感染者、其他免疫抑制患者和老年男性。这些疾病在KSHV流行率高的撒哈拉以南非洲和地中海地区以及男男性行为者中最为常见。已经开发了用于KSHV血清学诊断的各种测定来调查全球KSHV流行病学。通常使用利用一种裂解抗原（K8.1）和一种潜伏抗原（ORF 73）的ELISA。然而，一个更完整的表征所有KSHV抗原的免疫反应可能有重要的流行病学和临床应用。我们系统地表达和纯化了KSHV编码的85种蛋白中的73种，并分析了与健康受试者相比，KSHV相关恶性肿瘤患者的血清学反应。除了已知的K8.1、ORF 73和ORF 65之外，我们还发现了对ORF 38、ORF 61、ORF 59和K5的显着反应性。反应模式各不相同;然而，HIV感染者对更多抗原有反应，强度更大。接下来，我们开发了一种基于珠子的检测方法，可以同时检测一个小样本中的六种KSHV抗原。新工具可以改善KSHV的检测以及无症状感染和KSHV相关疾病的特征。
The Kaposi sarcoma associated herpesvirus (KSHV) genome encodes more than 85 open reading frames (ORFs). Serological evaluation of KSHV infection now generally relies on reactivity to just one latent and/or one lytic protein (commonly ORF73 and K8.1). Most of the other polypeptides encoded by the virus have unknown antigenic profiles. We have systematically expressed and purified products from 72 KSHV ORFs in recombinant systems and analyzed seroreactivity in US patients with KSHV-associated malignancies, and US blood donors (low KSHV seroprevalence population). We identified several KSHV proteins (ORF38, ORF61, ORF59 and K5) that elicited significant responses in individuals with KSHV-associated diseases. In these patients, patterns of reactivity were heterogeneous; however, HIV infection appeared to be associated with breadth and intensity of serological responses. Improved antigenic characterization of additional ORFs may increase the sensitivity of serologic assays, lead to more rapid progresses in understanding immune responses to KSHV, and allow for better comprehension of the natural history of KSHV infection. To this end, we have developed a bead-based multiplex assay detecting antibodies to six KSHV antigens. Kaposi sarcoma-associated herpesvirus (KSHV) is the cause of Kaposi sarcoma, primary effusion lymphoma and a form of multicentric Castleman's disease, affecting mainly persons with HIV, other immunosuppressed patients and elderly men. Such diseases are most common where KSHV prevalence is high, in sub-Saharan Africa and the Mediterranean, and amongst men who have sex with men. Various assays for the serodiagnosis of KSHV have been developed to investigate global KSHV epidemiology. ELISAs utilizing one lytic (K8.1) and one latent antigen (ORF73) are often used. However, a more complete characterization of immune responses to all KSHV antigens may have important epidemiologic and clinical applications. We systematically expressed and purified 73 of the 85 proteins encoded by KSHV and analysed serologic responses in patients with KSHV-associated malignancies compared to healthy subjects. We identified significant reactivity to ORF38, ORF61, ORF59 and K5, in addition to the known K8.1, ORF73 and ORF65. Reactivity patterns were varied; however, HIV infected individuals were reactive to more antigens, with greater intensity. Next, we developed a bead-based assay that can test a small sample simultaneously for six KSHV antigens. The new tool can improve the detection of KSHV and the characterization of asymptomatic infection and KSHV associated diseases.
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影响因子：
6.4
作者：
Biggar, RJ;Engels, EA;Goedert, JJ
通讯作者：
Goedert, JJ
DOI：
10.1128/cdli.7.3.427-435.2000
发表时间：
2000-05-01
期刊：
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY
影响因子：
--
作者：
Inoue, N;Mar, EC;Pellett, PE
通讯作者：
Pellett, PE
影响因子：
2.7
作者：
Hopkins, Ralph F.;Esposito, Dominic
通讯作者：
Esposito, Dominic
影响因子：
3.8
作者：
Malope, Babatyi I.;MacPhail, Patrick;Whitby, Denise
通讯作者：
Whitby, Denise
影响因子：
6.4
作者：
Burbelo, Peter D.;Issa, Alexandra T.;Yarchoan, Robert
通讯作者：
Yarchoan, Robert