Dominant human herpesvirus type 8 RNA transcripts in classical and AIDS-related Kaposi's sarcoma

Skin biopsy sections of Kaposi's sarcoma (KS) from 25 patients (5 AIDS-related, 20 classical cases) were histologically staged and hybridized in situ with oligonucleotide probes for constitutively transcribed human herpesvirus 8 (HHV-8) mRNA T0.7 and T1.1 using a colourimetric technique. T1.1 increases during experimental induction of the viral lytic phase in the HHV-8-infected lymphocytes of primary effusion lymphoma and its colourimetric detection in KS cells presumably corresponds to virion production. Immunostaining with anti-CD20, CD45RO, MAC 387, and α-smooth muscle actin was performed following T1.1 in situ hybridization (ISH). When the amount of T0.7 was above the detection threshold, the signal was made up of multiple coarse intranuclear dots in most spindle cells. Of the six early-stage lesions, none produced a T1.1 hybridization signal. Two of four AIDS-related and two of eight classical lesions with incipient spindle cell growth produced rare but distinct dense intranuclear T1.1 signals in endothelial cells lining narrow tubes. In contrast, eight of ten (all classical KS) mature spindle cell lesions displayed a signal, scattered in up to 2 per cent of spindled endothelial cells. Cell types other than endothelium produced no T1.1 hybridization signal in double stains. The results are consistent with other published data indicating latent HHV-8 infection in endothelium and its tumour cell progeny, with simultaneous virion production in a small subset of cells. Immunodeficiency may not influence the number of cells lytically infected with HHV-8 in early KS, in contradistinction to other herpesviruses with latent-lytic cycles. Copyright © 1999 John Wiley & Sons, Ltd.     

Human herpesvirus 8 genoprevalence in populations at disparate risks of Kaposi's sarcoma

The prevalence of human herpesvirus 8 (HHV-8) in populations at different risks of developing Kaposi's sarcoma (KS) was assessed using a protocol involving immunomagnetic fractionation of CD45+ blood cells prior to detection of the HHV-8 genome by nested PCR. Preliminary studies using blood of eight gay men infected by human immunodeficiency virus-1 (HIV-1) revealed that, for the detection of HHV-8 DNA derived from open reading frame (ORF) 26 of the HHV-8 genome, this protocol provided substantially higher rates (100%) compared to one involving red blood cell (RBC) lysis (0%) and to another requiring double density gradient centrifugation (DDGC) of leukocytes (13%). When the CD45+ fractionation protocol was applied to samples from 103 other HIV-1-infected patients (the vast majority of whom were gay men) and 100 blood donors, the ORF 26 DNA detection rates obtained were 37% and 8%, respectively. When DNA from the variable region 1 of ORF K1 was additionally amplified from samples of the blood donors, a detection rate of 9% was achieved. This rate was highly concordant with the ORF 26 DNA detection rate. Furthermore, the ORF K1 sequences were predominantly unique, assignable to genotypes A1, A4, and C3. When assays for anti-HHV-8 and anti-herpes simplex viruses (HSV) 1 and 2 were applied, significant concordances between HHV-8 DNA detection rates and those relating to anti-HHV-8 and to anti-HSV 1 and 2 were more frequently observed for HIV-1-infected patients than for blood donors. The higher-than-expected HHV-8 genoprevalence rate in blood donors requires further confirmation in view of its implications for post-transfusion HHV-8 transmission.     

Kaposi's sarcoma of the gastrointestinal tract: report of two cases and review of the literature

Involvement of Kaposi's sarcoma in the gastrointestinal tract is common in AIDS patients and can also occur in non-AIDS patients. However, the disease is usually asymptomatic and, due to tumor growth primarily in the submucosa, biopsy diagnosis is possible in less than 25%. In the present study, we describe two cases of Kaposi's sarcoma that were first diagnosed in the gastrointestinal tract of a 74-year-old patient who presented to the clinic with nausea and vomiting. On esophagogastroduodenoscopy, a lesion 0.7 cm in size was found. Histology revealed a Kaposi's sarcoma of the stomach with existing HHV8 infection, and there were negative tests for HIV. The second case is a 39-year-old patient with multiple lesions in the stomach and in the small and large intestine. The histology verified multiple Kaposi's sarcomas that were HHV 8-positive. Afterwards, the diagnosis of an HIV infection was made. Primary diagnosis of Kaposi's sarcoma of the gastrointestinal tract in HIV-negative patients is certainly rare and more frequently made in HIV patients. Nevertheless, Kaposi's sarcoma must always be considered in lesions of the gastrointestinal tract or in gastrointestinal bleeding and should lead to further elucidation of the causes.     

HHV8 and female Kaposi's sarcoma

Kaposi's sarcoma (KS) is an enigmatic tumour of uncertain histogenesis. Epidemiological data have long suggested that KS may be caused by an infectious agent, possibly sexually transmitted. Following the documentation of human herpesvirus 8 (HHV8) and its strong association with all forms of KS, it now appears that the putative agent has at last been identified. As KS is rare in females, a unique group was screened for the presence of HHV8 using both conventional solution-phase polymerase chain reaction (PCR) and the newly described technique of TaqMan® PCR. The presence of HHV8 was demonstrated in 10/12 of these female patients. This further supports the direct role of HHV8, in conjunction with cytokines and other factors, in the pathogenesis of KS. © 1997 John Wiley & Sons, Ltd.     

Salivary human herpesvirus 8 shedding in renal allograft recipients with Kaposi's sarcoma

Renal allograft recipients in the Middle East are at high risk of developing Kaposi's sarcoma. This report describes the extent of oral human herpesvirus 8 shedding and the genomic diversity of the virus in five Saudi Arabian kidney transplantation patients in whom Kaposi's sarcoma had developed. PCR protocols were applied to amplify three fragments of the viral genome from whole-mouth saliva, parotid saliva, buccal and palatal exfoliates, plasma, peripheral blood leukocytes and biopsy of the Kaposi's sarcoma lesion, and to quantify the viral load in whole-mouth saliva. Viral DNA was detected in all plasma and biopsy samples, 80% of whole-mouth saliva, 20% of each of the other oral samples, and none of the leukocyte samples. The viral load in the cell-free fraction of whole-mouth saliva ranged between approximately 1.2 x 10(3) and 2.2 x 10(6) genome-copies/ml. Genotypically distinct viral strains were evident: intra-lesionally in 1 patient; intra-orally in one patient; between an oral sample and biopsy in two patients; and in four patients, between an oral sample and plasma, and between plasma and biopsy. Thus, in the patients studied, salivary shedding of human herpesvirus 8 was frequent and could be extensive, and they were prone to multiple infections. Measures to curtail salivary viral transmission to pre- and post-transplantation patients might reduce the incidence of post-transplantation Kaposi's sarcoma.     

Quantification of human herpesvirus 8 by real-time PCR in blood fractions of AIDS patients with Kaposi's sarcoma and multicentric Castleman's disease

Few studies have assessed human herpesvirus 8 (HHV8) viremia levels in different HHV8-related pathologies, using sensitive and reproducible molecular assays. Our objective was to compare the HHV8 DNA load in serial blood samples (collected every 3 months for 1 year) from acquired immunodeficiency syndrome (AIDS) patients with Kaposi's sarcoma (KS) and multicentric Castleman's disease (MCD). The HHV8 viral load was determined in both peripheral blood mononuclear cells (PBMC) and plasma fractions, using a competitive real-time polymerase chain reaction (PCR) assay developed in a LightCycler instrument (Roche Diagnostics). In six subjects with limited or extensive KS while on highly active antiretroviral therapy, the HHV8 DNA load was either undetectable (<50 copies/10(5) cells) or low (1,000 copies in at least one of the samples from the two subjects with both KS and MCD. HHV8 DNA was detected in plasma only when the cellular viral load was >10,000 copies/10(5) cells. After chemotherapy, the HHV8 DNA load became undetectable in the MCD patients despite no changes in CD4 T-cell counts or highly active antiretroviral therapy (HAART) regimens. These results suggest that the pathogenesis of the two HHV8-associated diseases (i.e., KS and MCD) might be different, as only the latter was associated with important viremia in our patients.     

Detection of Merkel cell polyomavirus in Merkel cell carcinoma and Kaposi's sarcoma

Merkel cell carcinoma is a rare malignancy that sometimes occurs in the skin of elderly people. Recently, a new human polyomavirus, Merkel cell polyomavirus (MCPyV) was identified in Merkel cell carcinoma. In the present study, MCPyV‐DNA was detected in 6 of 11 (55%) cases of Merkel cell carcinoma by nested PCR and real‐time PCR. Histologically, MCPyV‐positive cases showed round and vesicular nuclei with a fine granular chromatin and small nucleoli, whereas MCPyV‐negative cases showed polygonal nuclei with diffusely distributed chromatin. Real‐time PCR analysis to detect the MCPyV gene revealed that viral copy numbers ranged 0.04–0.43 per cell in cases of Merkel cell carcinoma. MCPyV was also detected in 3 of 49 (6.1%) cases of Kaposi's sarcoma (KS), but not in 192 DNA samples of other diseases including 142 autopsy samples from 20 immunodeficient patients. The MCPyV copy number in KS was lower than that in Merkel cell carcinoma. PCR successfully amplified a full‐length MCPyV genome from a case of KS. Sequence analysis revealed that the MCPyV isolated from KS had 98% homology to the previously reported MCPyV genomes. These data suggest that the prevalence of MCPyV is low in Japan, and is at least partly associated with the pathogenesis of Merkel cell carcinoma. J. Med. Virol. 81:1951–1958, 2009. © 2009 Wiley‐Liss, Inc.     

Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV8)—a new human tumour virus

Recently, a novel DNA virus has been molecularly cloned from Kaposi's sarcoma (KS) tissue, a tumour common in acquired immune deficiency syndrome (AIDS). Analysis of the viral genome confirms that it is a relative of human herpesviruses and the virus has been designated HHV-8. Epidemiological evidence suggests a strong aetiological link between the presence of HHV-8 DNA and/or antibodies against the virus, and KS. Additional sequence analysis suggests that the HHV-8 genome contains sequences which encode a D type cyclin and a number of other genes potentially implicated in growth deregulation which may be relevant to its proposed role as a transforming virus. © 1997 John Wiley & Sons, Ltd.     

Genotypic and clinicopathological characterization of Kaposi's sarcoma‐associated herpesvirus infection in Japan

Kaposi's sarcoma‐associated herpesvirus (KSHV) is related causally to Kaposi's sarcoma, primary effusion lymphoma, and a subset of cases of multicentric Castleman's disease. As the numbers of acquired immunodeficiency syndrome (AIDS) patients have increased, KSHV‐associated diseases have also increased in Japan. Sporadic cases of classic Kaposi's sarcoma have also been reported in Japan. In the present study, the clinicopathological characteristics of 75 samples, comprising 68 cases of Kaposi's sarcoma, 5 cases of primary effusion lymphoma, and 5 cases of multicentric Castleman's disease were investigated. All of these cases were positive for KSHV by immunohistochemistry or PCR analysis. All fifty‐two of the AIDS‐associated Kaposi's sarcoma cases were males, whereas 7 of the 13 non‐AIDS‐associated Kaposi's sarcoma cases were females. The mean age of patients with AIDS‐associated Kaposi's sarcoma or primary effusion lymphoma was 46 years, whereas the mean age of patients with non‐AIDS‐associated Kaposi's sarcoma or primary effusion lymphoma was 71.8 and 97.5, respectively. KSHV genotypes were determined based on the sequence of variable region 1 in the K1 gene. Genotypes A and C of KSHV were detected in both AIDS‐ and non‐AIDS‐associated Kaposi's sarcoma. Genotype A was detected more frequently in AIDS‐associated cases than non‐AIDS‐associated cases, suggesting that genotype C is broadly distributed in Japan, and genotype A spreads among AIDS patients. Genotype D was detected only in non‐AIDS‐associated Kaposi's sarcoma. These data confirmed the difference between AIDS‐ and non‐AIDS‐associated KSHV diseases with regard to age of onset, gender, and genotypes in Japan. J. Med. Virol. 82:400–406, 2010. © 2010 Wiley‐Liss, Inc.     

Consistent polymerse chain reaction–single-strand conformation polymorphism pattern of human herpesvirus-8 in the course of classical Kaposi's sarcoma assumes its clonal origin

There is emerging evidence that Kaposi's sarcoma–associated herpesvirus (KSHV or HHV-8) has a central role in the pathogenesis of Kaposi's sarcoma (KS). The occurrence of HHV-8 in classical KS biopsies is reported irrespective of its clinical stage (patch, plaque, nodular). HHV-8 was detected in 25 of 28 formalin-fixed paraffin-embedded classical KS samples by nested polymerase chain reaction. In addition, in six patients multiple tumors were available (n = 21). Single-strand conformation polymorphism (SSCP) analysis of the amplicons showed uniform SSCP pattern of samples belonging to the same patient regardless of whether the KS was multiplex or developed again years after the first excision. Most of the SSCP patterns were confirmed by further sequence analysis. The presence of the same sequence variant of HHV-8 in various samples of the same patient supports the clonal origin of classical Kaposi's sarcoma. J. Med. Virol. 54:300–304, 1998. © 1998 Wiley-Liss, Inc.     

Co-expression of endothelial cell and macrophage antigens in Kaposi's sarcoma cells

Mutations in the p53 tumour suppressor gene, with consequent accumulation of the p53 protein, are frequently observed in non-small cell lung cancer (NSCLC). Little is known, however, about the timing of their appearance or their maintenance through cancer progression and metastatic spread. We have examined the normal epithelium and a panel of bronchial lesions, including dysplastic, neoplastic, and metastatic leisons, for p53 immunoreactivity and for expression of proliferating cell nuclear antigen (PCNA). No p53 immunoreactivity was found in normal and hyperplastic epithelium, nor in squamous metaplastic lesions. Twenty out of 30 invasive tumours and 13 out of 17 in situ carcinomas adjacent to an invasive tumour showed p53 immunoreactivity. There was a strict correlation between the level of p53 expression in the non-invasive and the invasive components of the tumours. Five out of eight pairs of primary tumours and matching metastases expressed p53, at identical levels in both compartments. These data indicate that p53 overexpression can occur in the earliest recognized phase of NSCLC and that the alteration is maintained during progression from in situ to invasive carcinoma and metastatic spread. PCNA expression increased from early to advanced phases of NSCLC. High PCNA immunoreactivity was observed in tumours expressing high p53 levels. A significant association was observed for PCNA expression between preinvasive and invasive lesions.     

Molecular epidemiology of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 strains from Russian patients with classic, posttransplant, and AIDS-associated Kaposi's sarcoma

We report the molecular characterization of 38 new Kaposi's sarcoma-associated herpesvirus (KSHV) strains from Russian patients with either classic (25 cases), epidemic/AIDS-associated (7 cases), or posttransplant/immunosuppressed patients (6 cases), or Kaposi's sarcoma (KS). While a complete sequence of the K1 gene (870 bp) was obtained from 30 strains, only partial sequences of the hypervariable regions VR1 (372 bp) and/or VR2 (381 bp) of the K1 gene were obtained from eight strains of KS paraffin blocks. Sequence comparison and phylogenetic studies indicate that the novel KSHV strains belong to either the A subtype (28 cases) or the C subtype (10 cases). Within the 28 strains of A subtype, 24 (86%) belong to the large A' subgroup, mostly A1 and A1' clades, and 4 belong to the A" subgroup, mostly A3 clade. Within the 10 strains of subtype C, 4 were of C' subgroup, and 6 of the C". Some molecular variants of subtype A' were observed, with 3 strains exhibiting an insertion of a single amino acid at the position 65 and 2 strains (both from AIDS-KS) with an unique deletion of 17 amino acids in the VR2 region. Polymerase chain reaction-based subtyping of the K14.1 genomic region indicated that most (23/32) of the novel strains belonged to the P subtype. The results indicate that despite a wide genetic diversity of A and C K1 subtypes of KSHV strains present in Russia, most are closely related and belong to the A1 or A1' molecular clades suggesting a common origin. This study also expands the data regarding the absence of any correlation between a K1 molecular subtype and a specific KS type (classic, epidemic, or posttransplant), as well as between the K1 and K14.1 molecular subtypes.     

Direct correlation between human herpesvirus-8 seroprevalence and classic Kaposi's sarcoma incidence in Northern Sardinia

The human herpesvirus-8 (HHV-8) has been associated with the development of Kaposi's sarcoma. A high incidence of classic Kaposi's sarcoma has been described in Sardinia, an island West of Italy's mainland. Different seroepidemiological analyses have reported that prevalence of HHV-8 infection varies worldwide: a high HHV-8 seroprevalence has been shown in Italy. The present survey was carried out to evaluate the correlation between HHV-8 infection and classic Kaposi's sarcoma incidence in northern Sardinia. Blood samples were collected from 226 healthy donors born and resident in five different areas of North Sardinia. Seroprevalence to HHV-8 was determined searching antibodies to viral lytic proteins by immunofluorescence in sera diluted at 1:10. Classic Kaposi's sarcoma incidence data spanning a period of 23 years were examined in the areas studied. The present screening revealed that seroprevalence was 35%, within a range of 15.3-46.3% in the five areas, although it should be considered that the seroprevalence to HHV-8 can be established more accurately by the combined use of different assays. Age emerged as an important risk factor. Indeed, subjects aged > 50 years showed a higher seroprevalence to HHV-8 as compared with younger individuals. A strong direct correlation between HHV-8 prevalence and classic Kaposi's sarcoma incidence has been also observed. The wide diffusion of HHV-8 in Sardinia appears to represent an important factor in the high incidence of classic Kaposi's sarcoma reported in the island. However, additional co-factors, such as age, sex, genetic traits, or viral strain pathogenicity, are likely to play a role in the development of the disease.     

Latent and lytic HHV-8 mRNA expression in PBMCs and Kaposi's sarcoma skin biopsies of AIDS Kaposi's sarcoma patients

Human herpes virus 8 (HHV-8) is associated with all clinical forms of Kaposi's sarcoma. HHV-8 DNA is present in Kaposi's sarcoma biopsies and is observed regularly in saliva and less consistently in blood of Kaposi's sarcoma patients. The expression pattern of latent (ORF 73) and lytic (vGCR, vBcl-2, and vIL-6) HHV-8 mRNA was studied in peripheral blood mononuclear cell (PBMC) samples and Kaposi's sarcoma skin biopsies from 11 AIDS Kaposi's sarcoma patients with four different nucleic acid sequence-based amplification (NASBA) assays. Patients were divided into groups according to the clinical stage of Kaposi's sarcoma (stage I-IV). All biopsies were positive for two or more of the mRNA measured. No clear difference could be seen in the expression pattern in the lesions of the different clinical stages. In the corresponding PBMC samples, very little or no mRNA was measurable in the patients with Kaposi's sarcoma stage I or II, whereas patients with more advanced Kaposi's sarcoma (stage III or IV) had more detectable mRNA in the PBMCs. Thus, the HHV-8 DNA load in the PBMCs increases in more advanced Kaposi's sarcoma, as does the frequency of mRNA detection in PBMCs.     

Thrombospondin-1 inhibits Kaposi's sarcoma (KS) cell and HIV-1 Tat-induced angiogenesis and is poorly expressed in KS lesions

Kaposi's sarcoma (KS), a neoplasm often associated with iatrogenic and acquired immunosuppression, is characterized by prominent angiogenesis. Angiogenic factors released by both KS and host cells, as well as HHV-8 and HIV viral products, have been implicated in the pathogenesis of this lesion. Angiogenesis is the result of imbalance among angiogenesis promoters and inhibitors, which disrupts homeostasis. The aim of this study was to investigate the expression and mechanism of KS control of thrombospondin-1 (TSP), a physiological inhibitor of angiogenesis. Immunohistochemical analysis of four KS lesions showed only spotty reactivity for TSP in the stroma and in less than 10 per cent of lesional blood vessels. In addition, the typical KS spindle cells were not stained. In agreement with these findings, decreased levels of TSP were measured with an ELISA assay in the supernatants of cultured KS cells, compared with endothelial cells. In vitro, TSP inhibited the endothelial cell proliferation and motility induced by KS cell supernatants. TSP also prevented endothelial cell motility induced by Tat, a product of HIV-1 endowed with angiogenic potential and implicated in the pathogenesis of AIDS-KS. In vivo, TSP inhibited the angiogenic activity exerted by Tat in the Matrigel sponge model. These results suggest that TSP down-regulation might be permissive for the development of KS-associated angiogenesis. Copyright © 1999 John Wiley & Sons, Ltd.     

Ultrastructural characterization of human herpesvirus 8 (Kaposi's sarcoma- associated herpesvirus) in Kaposi's sarcoma lesions: electron microscopy permits distinction from cytomegalovirus (CMV)

Kaposi's sarcoma (KS) has been shown by molecular techniques to be associated with infection with human herpesvirus 8 (HHV8/KSHV), but specific ultrastructural characterization of the virus has been impaired by the frequent presence in these lesions of other herpesviruses, particularly cytomegalovirus (CMV). Since the ultrastructural appearance of HHV8/KSHV has been studied in the cell line KS-1 uninfected with other viruses including CMV, it was possible to undertake a comparative study of CMV and HHV8/KSHV in KS lesions. HHV8/KSHV was sparsely present and lytic infection was restricted to endothelial cells. The following specific ultrastructural features allowed distinction between HHV8/KSHV and CMV: the viral particles were more delicate and less numerous in cases of HHV8/KSHV infection; the viral tegument was more electron-dense in CMV than in HHV8/KSHV; dense bodies characteristic of CMV were absent in HHV/KSHV; complete CMV viral particles were more variable in size and generally larger (150–200 nm) than HHV8/KSHV (120–150 nm); and finally, the viral envelope was more pleomorphic in CMV than in KSHV/HHV8. Similarities between CMV and HHV8/KSHV included the basic structure of the nucleocapsids and the presence of capsids lacking central DNA cores (so-called non-infectious enveloped particles). These observations show that electron microscopy can be used to identify HHV8/KSHV and confirm the relationship between HHV8/KSHV and KS. © 1997 John Wiley & Sons, Ltd.     

Comparison of human herpesvirus 8 and Epstein-Barr virus seropositivity among children in areas endemic and non-endemic for Kaposi's sarcoma

Human herpesvirus 8 (HHV-8) is the etiologic agent of Kaposi's sarcoma (KS). Several studies indicate horizontal HHV-8 transmission among children in areas where KS is endemic, but few studies have assessed acquisition of HHV-8 by children in low seroprevalence areas. Antibody screening was carried out for HHV-8 and Epstein-Barr virus (EBV) on 787 serum specimens from children living in two areas where HHV-8 is not endemic, the United States (US) and Germany, and on 184 specimens from children living in a KS-endemic area (Nigeria). For children in the US and Germany, the results showed low HHV-8 seroprevalence rates (3-4%). However, US children aged 6 months to 5 years had higher HHV-8 antibody titers than did 6-17-year-old children (P < 0.01), a finding consistent with more recent infections being detected in the younger children. Compared with seroprevalence rates and antibody titers in US and German children, those in Nigerian children were significantly higher, and seroprevalence increased with age. There was no evidence of cross-reactivity between assays for HHV-8 and EBV, despite the genetic similarity of these two herpesviruses. The data indicate that HHV-8 transmission among children where HHV-8 is not endemic occurs, but is uncommon. The findings also suggest that HHV-8 antibodies, as measured by current tests, may not persist for long periods in populations at low risk for KS and that vertical transmission is rare, although longitudinal studies are necessary to address directly these issues.     

斑点分子杂交检测HPV感染与宫颈癌的关系

采用ＤＮＡ－ＤＮＡ分子杂交技术，对经病理组织学确诊的慢性宫颈炎，宫颈癌和正常宫颈的宫颈活检组织中ＨＰＶ６，ＨＰＶ１１，ＨＰＶ１６，ＨＰＶ１８型ＤＮＡ进行同源序列检测，结果表明ＨＰＶ６，ＨＰＶ１１，ＨＰＶ１６，ＨＰＶ１８型ＤＮＡ的检出率在正常宫颈均为０；在慢性宫颈炎分别为１６．０９％，１２．６４％，１１．４９％，３．４５％；在宫颈癌组分别为３．９６％，１．９８％，４６．５３％，７．９２％。在宫颈癌组     

Human leukocyte antigen polymorphisms and Kaposi's sarcoma-associated herpesvirus infection outcomes: A call for deeper exploration

Host genetic background may influence the immunity to resist viral infection. As the most polymorphic loci in the entire human genome, the human leukocyte antigen (HLA) system plays an important role in innate and adaptive immune responses to many invading pathogens. Studies have shown that an association might exist between HLA polymorphisms and susceptibility to Kaposi's sarcoma-associated herpesvirus (KSHV) infection and associated diseases. However, discrepant conclusions were reached among different subjects with different detection methods. Therefore, it is now urgent to summarize current results and figure out the achievements and deficiencies of the existing research for the reference to future studies. A better understanding about the role of HLA polymorphisms in KSHV infection outcome would enable us to elucidate the pathways through which the virus evades the host defense system and improve strategies for the prevention and treatment of KSHV infection.