人类疱疹病毒8型ORF75亚型的研究进展

人类疱疹病毒8型是新发现的一种人类致瘤病毒,根据不同的开放阅读框架(open reading frames,ORFs)可以把HHV-8分为不同的亚型,近年来对ORF75亚型的大量研究表明其与HHV-8相关疾病的关系密切.     

人疱疹病毒8型—Kaposi肉瘤相关疱疹病毒及其相关疾病的研究进展

Kaposi肉瘤相关疱疹病毒,又称人疱疹病毒8型,最近来发现的一种新的肿瘤病毒,它参与了Kaposi肉瘤的发病机制,并与某些血液疾病,如原发性渗出性淋巴瘤及多中心Castleman病等有关。此病毒的一系列病毒基因能干扰细胞的生长和分化,但确切的致瘤因素仍在研究中。     

Kaposi肉瘤患者血清人类疱疹病毒8型的检测

目的：了解干扰素治疗Kaposi肉瘤近期疗效及其对血清HHV-8 DNA检测的影响。方法：主要应用干扰素治疗4例无明显内脏损害的新疆经典型Kaposi肉瘤患者，同时在治疗前后采用PCR法检测血清HHV-8 DNA特异性片段。结果：4例患者经干扰素治疗45d后，均有不同程度的近期疗效，主要表现在皮损色泽变暗、结节和斑块变软、变平，部分小结节消退，且均无新皮损发生。但淋巴水肿无明显改观。血清HHV-8 DNA特异性片段经PCR检测，治疗后全部转阴。结论：干扰素治疗可有效地清除Kaposi肉瘤患者血清中HHV-8感染，能缓解病情，防止Kaposi肉瘤多灶病状的发生。     

人疱疹病毒8型—Kaposi肉瘤相关疱疹病毒

从Ｋａｐｏｓｉ肉瘤中检出一种新的疱疹病毒，命名为Ｋａｐｏｓｉ肉瘤相关疱疹冱，又称人疱疹病毒８型，它可能参与Ｋａｐｏｓｉ肉瘤的发病机制，并与某些淋巴增生性疾病（ｂｏｄｙ－ｃａｖｉｔｙ－ｂａｓｅｄ淋巴瘤和多中心Ｃａｓｔｌｅｍａｎ病）有关，故认为它是一个新的ＤＮＡ肿瘤病毒。     

新疆Kaposi肉瘤组织内人类8型疱疹病毒DNA的PCR检测

近年来人们在Kaposi肉瘤(KS)组织内发现一种新的疱疹病毒——人类8型疱疹病毒(HHV-8), 但国内目前尚未见到有关KSHHV-8的研究报道, 因此我们对新疆KS组织进行了HHV-8DNA的PCR检测, 特报道如下.     

人类疱疹病毒8型ORF26基因亚型与Kaposi肉瘤的相关性研究

目的 明确Kaposi肉瘤患者感染的人类疱疹病毒8型（HHV-8）ORF26基因亚型分类，初步探讨其与Kaposi肉瘤不同临床分型及侵袭性的相关性。方法 对32例Kaposi肉瘤石蜡包埋组织进行HHV-8 DNA抽提、扩增、双向测序，使用DNAStar软件、Clustal W软件和PHYLIP软件包对测序结果进行系统发生学分析，从而确定HHV-8 ORF26基因亚型，最后运用Fisher确切概率法对结果进行统计学分析。结果 32例Kaposi肉瘤中有30例HHV-8阳性，阳性率为93.75%，其中6例艾滋病相关型患者HHV-8均阳性。30例HHV-8阳性患者中，17例为HHV-8 ORF26 A亚型，13例为C亚型。不同亚型间Kaposi肉瘤患者有无黏膜损害及临床分型的分布差异均无统计学意义（P > 0.05）。结论 Kaposi肉瘤患者感染HHV-8 ORF26亚型属于A亚型和C亚型，不同亚型与黏膜损害及临床分型无关。     

PCR检测Kaposi肉瘤患者血清人8型疱疹病毒

1994年Chang等从艾滋病患者的Kaposi肉瘤组织中分离到了两种独有的序列^[1],称为人8型疱疹病毒(HHV-8),目前认为可能是Kaposi肉瘤的病因.国内已有作者对新疆经典型Kaposi肉瘤病理组织内进行过HHV-8的PCR及原位PCR研究^[1-3],现对10例新疆经典型Kaposi肉瘤患者血清进行了HHV-8DNAPCR检测.     

Kaposi肉瘤组织人类疱疹病毒8型免疫组化检测

目的．探讨免疫组化检测Kaposi肉瘤（KS）组织人类疱疹病毒8型（HHV-8）的可行性及其诊断意义。方法采用免疫组化方法分别检测58例KS组织和40例化脓性肉芽肿组织中HHV-8的表达。结果①HHV-8在KS真皮瘤体中的表达阳性率为94．83％（55／58）,在化脓性肉芽肿表达均阴性,在KS组织和血管瘤组织瘤体中的表达差异有统计学意义（P〈0．05）。②HHV-8在KS组织表皮中表达阳性率为6．90％（4／58）,血管内皮细胞中的表达阳性率为91．38％（53／58）,真皮梭形细胞中表达阳性率为94．83％（55／58）。⑧结节期KS组织中表达HHV-8阳性的细胞所占比例较斑片期及斑块期明显增多,其差异有统计学意义（P〈0．05）。结论免疫组化方法检测HHV-8在KS的诊断中具有重要意义。     

人疱疹病毒8型-Kaposi肉瘤相关疱疹病毒

从Kaposi肉瘤中检出一种新的疱疹病毒,命名为Kaposi肉瘤相关疱疹病毒,又称人疱疹病毒8型。它可能参与了Kaposi肉瘤的发病机制。并与某些淋巴增生性疾病(body-cavity-based淋巴瘤和多中心Castleman病)有关。故认为它是一个新的DNA肿瘤病毒。     

Kaposi肉瘤组织内人疱疹病毒8型的K14.1基因型研究

目的:确定人疱疹病毒8 型K14.1基因等位基因型在Kaposi肉瘤中的分布,及与Kaposi肉瘤临床分型的关系.方法:使用酚-氯仿-异戊醇法对32例Kaposi肉瘤石蜡包埋组织进行病毒DNA提取,使用PCR法扩增K14.1基因片段,然后确定其等位基因型.结果:32 例中有27 例人疱疹病毒8型感染为阳性,阳性率为84.38%,其中5例艾滋病相关型KS患者HHV-8感染均为阳性,感染率100% ;在分析的27 例HHV-8病毒株中,24例为P等位基因型(包括5例艾滋病相关型KS患者皮损),3例为M等位基因型(均来自经典型KS).结论:本研究中,Kaposi肉瘤感染的人疱疹病毒8型的K14.1等位基因型以P等位基因型为主.     

人疱疹病毒8型ORF75基因亚型与Kaposi肉瘤的相关性研究

目的 探讨人类疱疹病毒8型(HHV-8)ORF75基因亚型,与Kaposi肉瘤不同临床分型及侵袭性的相关性.方法 对25例新疆Kaposi肉瘤石蜡包埋组织进行HHV-8 DNA抽提、扩增及双向测序,使用Clustal W软件和PHYLIP软件包对测序结果进行发生学分析,从而确定HHV-8 ORF75基因哑型.结果 25例Kaposi肉瘤中,21例HHV-8阳性,阳性率为84%,其中7例AIDS相关型Kaposi肉瘤患者HHV-8均阳性.21例HHV-8阳性患者中,18例为HHV-8 ORF75 A亚型,3例为C亚型;不同亚型间Kaposi肉瘤患者有无黏膜损害及临床分型的分布差异均无统计学意义(P＞0.05).结论 新疆Kaposi肉瘤患者感染HHV-8 ORF75亚型属于A亚型和C亚型,HHV-8 ORF75不同亚型可能与新疆Kaposi肉瘤黏膜损害及临床分型无关.     

Kaposi肉瘤组织内人类疱疹病毒8型K1基因型的初步分析

A5和C7亚型,与非洲和欧洲来源毒株的同源性很高.     

Two cases of Kaposi's sarcoma mimicking Stewart-Treves syndrome found to be human herpesvirus-8 positive.

Although angiosarcoma is the most frequent tumor arising in the clinical setting of chronic lymphedema, as in Stewart-Treves syndrome, Kaposi's sarcoma has also been reported in this setting, although rarely. We describe two women who developed Kaposi's sarcoma in the lymphedematous arm many years after surgery for breast cancer. Case 1 is a 92-year-old and Case 2 is an 81-year-old; they underwent left total mastectomy and axillary node dissection for infiltrating breast carcinoma in 1981 and 1982 respectively. At that time, neither patient received further treatment. Except for persistent lymphedema, both women did well until over fourteen years later when each noted the development of several purple asymptomatic plaques on the edematous arm. In both, the clinical diagnosis at the time of biopsy was angiosarcoma. However, histologic findings in both cases were typical for Kaposi's sarcoma. In addition, a nested polymerase chain reaction (PCR) for the detection of a 233bp segment of KSHV/HHV8 was performed on DNA extracted from the paraffin-embedded specimens and both cases were positive for this sequence. Histologic sections of both cases were also tested for KSHV by in situ hybridization and demonstrated a positive signal in the lesional cells in each case.     

Kaposi肉瘤组织内人类疱疹病毒8型的K15基因型研究

目的 了解Kaposi肉瘤组织中人类疱疹病毒8型(HHV-8)K15等位基因型分布情况,并初步探讨Kaposi肉瘤不同临床分型及临床表现与不同HHV-8 K15等位基因型的相关性.方法 采用酚-氯仿-异戊醇法对收集的27例Kaposi肉瘤石蜡包埋组织标本进行病毒DNA抽提,并使用巢式PCR扩增K15基因片段,然后测序并确定其等位基因型.结果 27例Kaposi肉瘤中有22例HHV-8感染为阳性,阳性率为81.48%,其中4例艾滋病-Kaposi肉瘤患者HHV-8感染均为阳性,感染率100%;在分析的22例HHV-8病毒株中,20例为P型,2例为M型;4例艾滋病-Kaposi肉瘤患者感染的均为P型HHV-8,2例M型感染者均为经典型Kaposi肉瘤患者.结论 Kaposi肉瘤组织内HHV-8的K15等位基因型主要是P型,也存在部分M型HHV-8感染者.4例艾滋病-Kaposi肉瘤患者感染的HHV-8均为P型.     

人疱疹病毒8型ORF26单核苷酸多态性研究

目的 探讨人疱疹病毒8型(HHV-8)ORF26的单核苷酸多态性,分析其与Kaposi肉瘤不同临床分型及黏膜侵袭性的相关性.方法 Kaposi肉瘤患者32例,其中经典型26例,艾滋病相关型6例.使用酚-氯仿-异戊醇方法对Kaposi肉瘤石蜡包埋组织进行HHV-8 DNA抽提,采用巢式PCR方法扩增ORF26基因并双向测序,使用DNAStar软件和Clustal W软件分析ORF26基因的单核苷酸多态性.运用Fisher确切概率法对结果进行统计学分析.结果 ORF26基因研究发现,32例Kaposi肉瘤患者中HHV-8阳性30例,6例艾滋病相关型HHV-8均为阳性.30例患者的病毒株中,HHV-8 ORF26基因SNP主要集中在981T/C( 12例)、1086C/T(12例)、1139A/C(12例);HHV-8 ORF26基因单核苷酸多态性在不同临床分型或有无黏膜损害的Kaposi肉瘤之间的差异无统计学意义.结论 HHV-8 ORF26基因单核苷酸多态性可能与Kaposi肉瘤不同临床分型和黏膜侵袭性无关.     

Further confirmation of the association of human herpesvirus 8 with Kaposi's sarcoma

Recently, a new herpesvirus-like DNA sequence named Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8) has been isolated from almost all cases of Kaposi's sarcoma (KS). It has not been found in most benign and malignant cutaneous hemangioproliferative disorders other than KS. To further verify the specificity of the association of this new viral DNA with KS, we examined in total 42 cases of vascular neoplasms of endothelial derivation using nested polymerase chain reaction (PCR) for the presence of a 233-bp segment of this KSHV/HHV8 on paraffin-embedded specimens. In our investigation, we added an additional step to conventional PCR protocol that uses UV light to pretreat all the PCR regeants except Taq DNA polymerase and the target DNA to eliminate the false positives caused by trace contamination. All 15 cases of typical KS, both AIDS and non-AIDS related, as well as 4 cases of atypical vascular tumors suspicious of KS, were positive for this KSHV/HHV8 DNA sequence. The remaining 23 cases of hemangioproliferative disorders other than KS, including angiosarcoma, capillary hemangioma, angiolymphoid hyperplasia with eosinophilia, epithelioid hemangioma, histiocytoid hemangioma, hemangioendothelioma, and microvenous hemangioma, were negative for HHV8. These results confirm the previous observation that KSHV/HHV8 is specific for KS within hemangioproliferative cutaneous disorders, and PCR for detection of KSHV/HHV8 might be used as an additional diagnostic tool in distinguishing KS.     

Injection of human herpesvirus-8 in human skin engrafted on SCID mice induces Kaposi's sarcoma-like lesions

Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8) has been implicated in the development of Kaposi's sarcoma (KS) and several B-cell lymphoproliferative diseases. Serologic and molecular genetic association data has implicated HHV-8 as the causal agent of KS, but its role in the development of KS lesions is not understood. To examine the etiology of KS, HHV-8 was injected into normal human skin transplanted onto SCID mice. Injection of HHV-8 induced lesion formation that is morphologically and phenotypically consistent with KS, including the presence of angiogenesis and spindle-shaped cells latently infected with HHV-8. These findings suggest that HHV-8 is indeed the etiologic agent of KS, and that the virus plays an important role in initiation of this disease.     

Kaposi's sarcoma and other manifestations of human herpesvirus 8

Kaposi's sarcoma (KS) was described by Moritz Kaposi in 1872 and was known for an entire century as a rare disorder of older men usually of Eastern European, Mediterranean, and/or Jewish origin. In the early 1980s, the prevalence of KS began to increase dramatically and soon became the most common malignancy in patients with AIDS, especially those who were male homosexuals. In 1994, a new human herpesvirus (HHV) was found to be present in almost 100% of KS lesions. This virus was found to be a gammaherpesvirus, closely related to Epstein-Barr virus, and was designated HHV-8. Subsequently, HHV-8 DNA was found in almost all specimens of classic KS, endemic KS, and iatrogenic KS, as well as epidemic KS (ie, AIDS KS). It is now believed that HHV-8 is necessary, but not sufficient, to cause KS and that other factors such as immunosuppression play a major role. The use of highly active antiretroviral therapy (HAART) since 1996 has markedly reduced the prevalence of AIDS KS in western countries, but because 99% of the 40 million patients with AIDS in the world cannot afford HAART, KS is still a very common problem. Primary effusion lymphoma and multicentric Castleman's disease are also thought to be due to HHV-8. Although HHV-8 DNA has been described in a number of other cutaneous disorders, there is little evidence that HHV-8 is of etiologic significance in these diseases. The mechanism by which HHV-8 causes KS, primary effusion lymphoma, and multicentric Castleman's disease is not well understood but is thought to involve a number of molecular events, the study of which should further our understanding of viral oncology. (J Am Acad Dermatol 2002;47:641-55.) Learning objective: At the completion of this learning activity, participants should be familiar with Kaposi's sarcoma and other manifestations of human herpesvirus 8.