Latent Antigens Research Articles

Epstein-Barr Virus Nuclear Antigen 3C Facilitates G1-S Transition by Stabilizing and Enhancing the Function of Cyclin D1

EBNA3C, one of the Epstein-Barr virus (EBV)-encoded latent antigens, is essential for primary B-cell transformation. Cyclin D1, a key regulator of G1 to S phase progression, is tightly associated and aberrantly expressed in numerous human cancers. Previously, EBNA3C was shown to bind to Cyclin D1 in vitro along with Cyclin A and Cyclin E. In the present study, we provide evidence which demonstrates that EBNA3C forms a complex with Cyclin D1 in human cells. Detailed mapping experiments show that a small N-terminal region which lies between amino acids 130–160 of EBNA3C binds to two different sites of Cyclin D1- the N-terminal pRb binding domain (residues 1–50), and C-terminal domain (residues 171–240), known to regulate Cyclin D1 stability. Cyclin D1 is short-lived and ubiquitin-mediated proteasomal degradation has been targeted as a means of therapeutic intervention. Here, we show that EBNA3C stabilizes Cyclin D1 through inhibition of its poly-ubiquitination, and also increases its nuclear localization by blocking GSK3β activity. We further show that EBNA3C enhances the kinase activity of Cyclin D1/CDK6 which enables subsequent ubiquitination and degradation of pRb. EBNA3C together with Cyclin D1-CDK6 complex also efficiently nullifies the inhibitory effect of pRb on cell growth. Moreover, an sh-RNA based strategy for knock-down of both cyclin D1 and EBNA3C genes in EBV transformed lymphoblastoid cell lines (LCLs) shows a significant reduction in cell-growth. Based on these results, we propose that EBNA3C can stabilize as well as enhance the functional activity of Cyclin D1 thereby facilitating the G1-S transition in EBV transformed lymphoblastoid cell lines.

Risk Factors Influencing Antibody Responses to Kaposi's Sarcoma-Associated Herpesvirus Latent and Lytic Antigens in Patients Under Antiretroviral Therapy

Kaposi's sarcoma-associated herpesvirus (KSHV) seropositivity and lytic antibody titer are predictors for Kaposi's sarcoma. We examined demographic, viral, and immunologic factors that influence KSHV latent and lytic antibodies in HIV-infected patients. Detection rate of KSHV latent but not lytic antibodies was lower in patients with CD4 cells/mm3 less than 200 than greater than 200 (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.11-0.61) and CD8 cells/mm3 less than 400 than greater than 400 (OR, 0.26; 95% CI, 0.07-0.67). Overall seropositivity rate was higher in patients with CD4 cells/mm3 less than 200 than greater than 200 (OR, 2.34; 95% CI, 1.37-4.02) and HIV copies/mL greater than 400 than less than 400 (OR, 1.70; 95% CI, 1.09-2.65). Lytic antibody level was inversely correlated with CD4 count (P < 0.001). Lytic seropositivity (OR, 2.47; 95% CI, 1.35-4.50) and antibody level (adjusted difference mean optical density, 0.324; 95% CI, 0.16-0.46) were higher in patients with HIV infection greater than 15 than less than 15 years. Hispanics had higher lytic seropositivity rate (OR, 1.71; 95% CI, 1.07-2.73) and antibody level (adjusted difference mean optical density, 0.111; 95% CI, 0.03-0.18) than non-Hispanics. Lower CD4 and CD8 counts impair antibody response to KSHV latent antigens. Immune deterioration, long-term HIV infection, and Hispanic status are risk factors for Kaposi's sarcoma predictors.

Evaluation of Epstein-Barr Virus Latent Membrane Protein 2 Specific T-Cell Receptors Driven by T-Cell Specific Promoters Using Lentiviral Vector

Transduction of latent membrane protein 2 (LMP2)-specific T-cell receptors into activated T lymphocytes may provide a universal, MHC-restricted mean to treat EBV-associated tumors in adoptive immunotherapy. We compared TCR-specific promoters of distinct origin in lentiviral vectors, that is, Vβ6.7, delta, luria, and Vβ5.1 to evaluate TCR gene expression in human primary peripheral blood monocytes and T cell line HSB2. Vectors containing Vβ 6.7 promoter were found to be optimal for expression in PBMCs, and they maintained expression of the transduced TCRs for up to 7 weeks. These cells had the potential to recognize subdominant EBV latency antigens as measured by cytotoxicity and IFN-γ secretion. The nude mice also exhibited significant resistance to the HLA-A2 and LMP2-positive CNE tumor cell challenge after being infused with lentiviral transduced CTLs. In conclusion, LMP2-specific CTLs by lentiviral transduction have the potential use for treatment of EBV-related tumors.

Separating latent and acute TB

In theory, immunodiagnosis should be able to discriminate between latent and acute TB, because the immunopathoogic nature of the disease means there must be significant differences in either the type and/or magnitude of immune response that develop. But so far we have not been able to pinpoint them. Our investigations of immune responses after infection suggest that in a substantial number of former TB patients, strong antigen recognition persists at least 20 years post-treatment without signs of recurrent illness. In addition, antigen-specific CD4 and CD8 memory T-cells could be detected for at least two years post-infection. In a study published in 2001, we found that healthy household contacts who responded most strongly to ESAT-6 were more likely to progress to disease in a short time, but others who showed changes in their X-rays (meaning that they had been infected and even developed some pathology) remained otherwise healthy. An important question is whether this group is representative of natural latent infection. If that is so, similar people should be detectable in the general population and so our team looked at ESAT-6 responses in community controls. We found that although the responses to ESAT-6 were lower overall in the general population, a substantial subgroup were strongly positive. Our team’s assumption is that these individuals have latent disease. Given the results of our research, we have developed a model for analyzing latent TB infection. After initial exposure, two-thirds of the individuals exposed to TB do not apparently skin-test convert nor become ESAT-6 positive: if they have had an infection, early bacterial growth was presumably arrested fairly quickly. It is not possible to tell if they have latent TB because immunologically, they cannot be distinguished from uninfected individuals. Of the remaining individuals exposed, roughly five percent experience early bacterial growth that is not contained and, if not treated, progresses to clinical illness. In the remainder, subsequent bacterial growth is contained, symptoms abate, but latent infection is established and approximately two percent experience re-activation of the disease at a later time. The rest remain healthy, but have latent infection, which is discernible because immunologically these individuals tend to express elevated levels of interferon-gamma (IFN-γ), interleukin-12 (IL-12), IL-4 and IL-482 and strongly recognize latency antigens. These individuals are the focus of intense study because they represent natural immunity in action.

Protective and Predisposing HLA Alleles In Dutch Classical Hodgkin Lymphoma Patients

AbstractAbstract 749Classical Hodgkin lymphoma (cHL) is characterized by an overwhelming reactive infiltrate and the involvement of Epstein Barr virus (EBV) as a causative agent in a proportion of patients. We previously did a population-based genetic screening study of the Human Leukocyte Antigen (HLA) region in Dutch cHL patients and found a strong association between HLA class I (HLA-A1) and susceptibility to EBV+ cHL. This association might be explained by the known lack of HLA-A1 restricted T cell responses to EBV latent antigens. We now performed a case-control study to determine allele frequencies of all major HLA class I and class II genes in this cHL population. HLA genotyping of 294 cHL patients was performed by a polymerase chain reaction-based sequence-specific oligonucleotide probe hybridization (PCR-SSOP) approach in Luminex assays. The resulting single nucleotide polymorphism (SNP) data were converted into two-digit HLA typing for the HLA class I and class II genes. Phenotype frequencies of serologically defined HLA-A, HLA-B and HLA-DR blood donors were retrieved from the database of the blood bank of the University Medical Center Groningen. Allele frequency differences between these controls and cHL patients (total group and EBV+ and EBV- subgroups separately) were analyzed by Chi-square tests. In addition, we analyzed the HLA genotyping data for every PCR-SSOP probe to assess potential differences between the EBV+ and EBV- cHL group using PLINK software. Frequencies of HLA-DR4 and HLA-DR7 were significantly decreased and HLA-B5 and HLA-B37 were significantly increased in cHL as compared to the controls. In EBV+ cHL, HLA-A1, HLA-B37 and HLA-DR10 frequencies were significantly increased and HLA-A2 was decreased. An increase in HLA-B8, an allele that can present EBV peptides and that usually is in strong linkage disequilibrium with HLA-A1, was not present in these patients. In EBV- cHL, HLA-DR5 was significantly more common and HLA-DR4 was underrepresented. The SNP analysis revealed significant differences for 16 HLA-A probes between EBV+ and EBV- cHL. Eight probes that represented a high susceptibility for EBV+ cHL were specific for HLA-A1, whereas the other 8 probes correlated with a low risk for EBV+ cHL and were specific for HLA-A2. Most of the corresponding SNPs had a presumed antigenic peptide or T cell receptor binding function. In conclusion, the current study demonstrates that certain HLA alleles are protective or predisposing for cHL with specific associations for the EBV+ and EBV- cHL subgroups. The genotype analysis indicates that the complete HLA-A1 and HLA-A2 alleles are more important than individual T-cell receptor or antigen binding polymorphisms for the association with EBV+ cHL. Disclosures:No relevant conflicts of interest to declare.

Covalent modification by SUMO is required for efficient disruption of PML oncogenic domains by Kaposi's sarcoma-associated herpesvirus latent protein LANA2

The multifunctional Kaposi's sarcoma-associated herpesvirus (KSHV) latent protein latency-associated nuclear antigen 2 (LANA2) has a critical role in KSHV-induced B-cell malignancies. LANA2 increases the level of small ubiquitin-like modifier (SUMO)2-ubiquitin-modified PML and induces the disruption of PML oncogenic domains (PODs) by a process that requires a non-covalent SUMO interaction domain (SIM) in LANA2. We now demonstrate that LANA2 is covalently conjugated to SUMO1 and SUMO2 both in vitro and in latently KSHV-infected B-cells. We show that a LANA2 SIM mutant exhibits a slightly altered sumoylation pattern, which suggests that non-covalent SUMO interactions represent a mechanism for determining SUMO substrate recognition and modification. In addition, several lysine residues were mapped as SUMO conjugation sites. A sumoylation-deficient mutant shows impaired ability to induce disruption of PODs, which suggests that either directly bound or covalently conjugated SUMO moieties may act as a bridge for interaction between LANA2 and other SUMO-modified or SUMO-interacting proteins required for disruption of PODs.

Reconstitution of immune responses against Kaposi sarcoma-associated herpesvirus

Reconstitution of immune responses against Kaposi sarcoma-associated herpesvirus

Kaposi's Sarcoma Associated-Herpes Virus (KSHV) Seroprevalence in Pregnant Women in South Africa

BackgroundFactors previously associated with Kaposi's sarcoma-associated herpesvirus (KSHV) transmission in Africa include sexual, familial, and proximity to river water. We measured the seroprevalence of KSHV in relation to HIV, syphilis, and demographic factors among pregnant women attending public antenatal clinics in the Gauteng province of South Africa.MethodsWe tested for antibodies to KSHV lytic K8.1 and latent Orf73 antigens in 1740 pregnant women attending antenatal clinics who contributed blood to the "National HIV and Syphilis Sero-Prevalence Survey - South Africa, 2001". Information on HIV and syphilis serology, age, education, residential area, gravidity, and parity was anonymously linked to evaluate risk factors for KSHV seropositivity. Clinics were grouped by municipality regions and their proximity to the two main river catchments defined.ResultsKSHV seropositivity (reactive to either lytic K8.1 and latent Orf73) was nearly twice that of HIV (44.6% vs. 23.1%). HIV and syphilis seropositivity was 12.7% and 14.9% in women without KSHV, and 36.1% and 19.9% respectively in those with KSHV. Women who are KSHV seropositive were 4 times more likely to be HIV positive than those who were KSHV seronegative (AOR 4.1 95%CI: 3.4 - 5.7). Although, women with HIV infection were more likely to be syphilis seropositive (AOR 1.8 95%CI: 1.3 - 2.4), no association between KSHV and syphilis seropositivity was observed. Those with higher levels of education had lower levels of KSHV seropositivity compared to those with lower education levels. KSHV seropositivity showed a heterogeneous pattern of prevalence in some localities.ConclusionsThe association between KSHV and HIV seropositivity and a lack of common association with syphilis, suggests that KSHV transmission may involve geographical and cultural factors other than sexual transmission.

Patterns of antibodies against latent and lytic antigens of human herpesvirus 8 in an endemic population and patients with Kaposi's sarcoma in Mozambique

The patterns of antibodies against latent and lytic antigens of human herpesvirus 8 (HHV-8) were assessed using immunofluorescence assays of samples from 155 persons seropositive for HHV-8 seen at public health centers and 24 patients with Kaposi's sarcoma (KS) from Mozambique. Of the 155 persons without KS, 48 (31%) had antibodies against latent antigens only, 29 (18.7%) had antibodies against lytic antigens only, and 78 (50.3%) had antibodies against both types of antigen. The HHV-8 antibody titer tended to increase with age until age 40, after which it began to decrease. High titers of antibodies against latent and lytic antigens of HHV-8 were detected mostly in persons co-infected with HIV, and these increased titers could have a predictive value. All patients with KS except four patients who were seronegative for HHV-8 had elevated titers of HHV-8 antibodies, predominantly against latent antigens. The data suggest the potential for an increase in the development of KS in this endemic area for HHV-8.

Distinct Profiles of Antibodies to Kaposi Sarcoma–Associated Herpesvirus Antigens in Patients with Kaposi Sarcoma, Multicentric Castleman Disease, and Primary Effusion Lymphoma

Antibody responses against lytic and latent Kaposi sarcoma (KS)-associated herpesvirus antigens were investigated in patients with KS, multicentric Castleman disease (MCD), and primary effusion lymphoma. Antibodies against the lytic antigen K8.1 were 5-fold higher in patients with MCD than those with KS, whereas antibodies to the sum of latent antigens v-cyclin and LANA were 27-fold higher in patients with KS, compared with patients with MCD (P < 001). The sum of anti-v-cyclin and anti-LANA antibody titers discriminated patients with KS from those with MCD and KS with 93% sensitivity and 83% specificity. These results suggest that antibody responses to lytic and latent KS-associated herpesvirus antigens differ in these diseases.

Enhanced protection against tuberculosis by vaccination with recombinant BCG over-expressing HspX protein

Immunization with Mycobacterium bovis Bacille Calmette–Guerin (BCG) did not induce adequate Th1 responses to the latency antigen, HspX of M. tuberculosis. To increase the immunogenicity and protective efficacy of BCG, a recombinant BCG strain over-expressing antigen HspX (rBCG::X) was constructed. The recombinant strain rBCG::X expressed high levels of both HspX protein in the cytosol and Ag85B protein in the cytosol and supernatant. Mice vaccinated with rBCG::X produced a more consistent and enduring protective effect against infection with M. tuberculosis, showing lower bacterial load in lung and less severe lung pathology, than the control mice vaccinated with BCG strain containing the vector pMV261. The long-term protection induced by rBCG::X was associated with significant increases in antigen-specific IFN-γ to both HspX and Ag85B proteins, while PPD-specific IFN-γ responses declined. Our results suggest that latency antigens of M. tuberculosis may be promising targets for developing more effective recombinant BCG strains to protect against TB.

Human peripheral blood and bone marrow Epstein–Barr virus‐specific T‐cell repertoire in latent infection reveals distinct memory T‐cell subsets

EBV infection leads to life-long viral persistence. Although EBV infection can result in chronic disease and malignant transformation, most carriers remain disease-free as a result of effective control by T cells. EBV-specific IFN-gamma-producing T cells could be demonstrated in acute and chronic infection as well as during latency. Recent studies, however, provide evidence that assessing IFN-gamma alone is insufficient to assess the quantity and quality of a T-cell response. Using overlapping peptide pools of latent EBV nuclear antigen 1 and lytic BZLF-1 protein and multicolor flow cytometry, we demonstrate that the majority of ex vivo EBV-reactive T cells in healthy virus carriers are indeed IL-2- and/or TNF-producing memory cells, the latter being significantly more frequent in BM. After in vitro expansion, a substantial number of EBV-specific CD4(+) and CD8(+) T cells retained a CC-chemokine receptor 7 (CCR7)-positive memory phenotype. Based on their cytokine profiles, six different EBV-specific T-cell subsets could be distinguished with TNF-single or TNF/IL-2-double producing cells expressing the highest CCR7 levels resembling early-differentiated memory T cells. Our study delineates the memory T-cell profile of a protective immune response and provides a basis for analyzing T-cell responses in EBV-associated diseases.

DosR-regulon genes induction in Mycobacterium bovis BCG under aerobic conditions

In this report we demonstrated that under aerobic conditions, Mycobacterium bovis BCG expressing an hsp60-driven second copy of the hypoxia-related transcriptional regulator DosR increased 2-fold or greater the expression of 38 out of the 48 genes belonging to the DosR regulon, including the latency antigens Rv1733c, Rv2029, Rv2627, and Rv2628. Expression of DosR under these conditions slightly delayed in vitro growth, but did not promote a non-replicating state as opposed to microaerobic and hypoxic adaptation. Our results suggest BCG producing DosR can be cultured under standard in vitro conditions, allowing evaluation of this strain as a latency-specific vaccine candidate.

Diffuse large B-cell lymphoma of non-germinal center B-cell type of the heart in an immunocompetent woman: an autopsy case

Primary lymphoma of the heart is extremely rare and almost always occurs in immunodeficient persons. The author reports a very rare autopsy case of primary diffuse large B-cell lymphoma in an immunocompetent woman. A 55-year-old woman presented with chest pain and arrhythmia. Various imaging modalities including US, CT, MRI, and gallium-scintigraphy revealed a mass in the right atrium and pericardial effusion. No tumor formations were recognized in other organs. Pericardial effusion cytology revealed malignant large lymphoid cells of B-cell type positive for CD20. Laboratory data did not reveal immunosuppression, and human immunodeficiency virus was negative. Therefore, a clinical diagnosis of primary heart lymphoma was made. The patient was treated with chemo-radiation, but died of heart failure 4 years after the first presentation. An autopsy revealed a tumor formation (4 × 5 × 6 cm) in the right atrium and ventricle of the heart. No tumor formation was recognized in other organs. Histological and immunohistochemical studies showed that the cardiac tumor was diffuse large B-cell lymphoma of non-germinal center B-cell type; tumor cells were positive for CD45, CD20, CD79α, bcl-2, and λ-chain, but negative for EBV latent membrane antigen 1, CD10, bcl-6 and MUM1. Epstein-Barr virus protein and DNA were negative by immunohistochemistry and in situ hybridization. It was suggested that primary lymphoma of the heart may occur in immunocompetent persons. This is the first report of diffuse large B-cell lymphoma of the heart with a classification of non- or germinal center B-cell type.

Follicular dendritic cells in multicentric Castleman disease present human herpes virus type 8 (HHV8)‐latent nuclear antigen 1 (LANA1) in a proportion of cases and is associated with an enhanced T‐cell response

Multicentric Castleman disease (MCD) is a rare human herpes virus type 8 (HHV8)-associated lymphoproliferative disorder that occurs more frequently in patients infected with human immunodeficiency virus (HIV). In tissue samples, HHV8-infected plasmablasts localise to the mantle zones of the lymphoid follicles. We revisited the immunohistological features in 25 lymph node (LN) and three spleen samples of MCD. In five (20%) LN and one (33%) spleen sample, HHV8 latent nuclear antigen 1 (LANA1) staining was also noted on the follicular dendritic cells (FDC). The HHV8-positive FDC subgroup of patients had significantly higher numbers of CD3-positive T cells infiltrating the follicles when compared to the HHV8-negative FDC subgroup (P = 0.047). Furthermore, the numbers of HHV8-positive plasmablasts and serum HHV8 viral copy numbers were lower among the HHV8-positive FDC subgroup when compared to the HHV8-negative FDC subgroup (not statistically significant). Our findings show, for the first time, possible 'presentation' of an HHV8 antigen by FDCs in MCD.

Rare Primary Effusion Lymphoma Associated with HHV-8 in Japan

We describe a 62-year-old man infected with human immunodeficiency virus (HIV)-1 who developed primary effusion lymphoma (PEL). Pleural effusion contained atypical lymphoid cells with human herpesvirus (HHV)-8 latent nuclear antigen (LANA)(+). Radiological examination revealed pleural and pericardial effusion, but no evidence of tumor mass or lymph node enlargement. The patient was administered with highly active anti retroviral therapy (HAART) and THP-COP therapy, resulting in complete remission. The prevalence of HHV-8 infection among HIV positive individuals is higher than in the general population in Japan. Although PEL is extremely rare in Japan, the incidence might increase in the future.

In vivo persistence and protective efficacy of the Bacille Calmette Guérin vaccine overexpressing the HspX latency antigen

New strategies to control infection with Mycobacterium tuberculosis, the causative agent of tuberculosis, are urgently required, particularly in areas where acquired immune immunodeficiences are prevalent. In this report we have determined if modification of the current tuberculosis vaccine, Mycobacterium bovis BCG, to constitutively express the mycobacterial HspX latency antigen altered its protective effect against challenge with virulent M. tuberculosis. Overexpression of M. tuberculosis HspX in BCG caused reduced growth in aerated cultures compared to control BCG, but growth under limited oxygen availability was not markedly altered. Upon infection of mice, BCG:HspX displayed tissue- specific attenuation compared to control BCG, with reduced growth within the lung and liver but not the spleen. Both BCG:HspX and control BCG protected mice against aerosol M. tuberculosis challenge to a similar extent, however, immunodeficient mice infected with BCG:HspX survived significantly longer than mice infected with the control BCG strain. Therefore, altering the in vivo persistence of BCG by overexpression of HspX may be one important step towards developing a new tuberculosis vaccine with an improved safety profile and suitable protective efficacy against M. tuberculosis infection.

Induction of Protective Immunity against Murine Gammaherpesvirus 68 Infection in the Absence of Viral Latency

Human gammaherpesviruses, Epstein-Barr virus, and human herpesvirus 8/Kaposi's sarcoma-associated herpesvirus are important pathogens associated with diseases, including lymphomas and other malignancies. Murine gammaherpesvirus 68 (MHV-68) is used as an experimental model system to study the host immune control of infection and explore novel vaccine strategies based on latency-deficient live viruses. We studied the properties and the potential of a recombinant MHV-68 (AC-RTA) in which the genes required for persistent infection were replaced by a constitutively expressed viral transcription activator, RTA, which dictates the virus to lytic replication. After intranasal infection of mice, replication of AC-RTA in the lung was attenuated, and no AC-RTA virus or viral DNA was detected in the isolated splenocytes, indicating a lack of latency in the spleen. Infection of the AC-RTA virus elicited both cellular immune responses and virus-specific IgG at a level comparable to that elicited by infection of the wild-type virus. Importantly, vaccination of AC-RTA was able to protect mice against subsequent challenge by the wild-type MHV-68. AC-RTA provides a vaccine strategy for preventing infection of human gammaherpesviruses. Furthermore, our results suggest that immunity to the major latent antigens is not required for protection.

Response to Rv2628 latency antigen associates with cured tuberculosis and remote infection

Interferon-gamma release assays based on region of difference 1 antigens have improved diagnosis of latent tuberculosis infection (LTBI). However, these tests cannot discriminate between recently acquired infection (higher risk of progression to active tuberculosis) and remote LTBI. The objective of the present study was to evaluate the T-cell interferon-gamma responses to Mycobacterium tuberculosis DosR-regulon-encoded antigens (latency antigens) compared with QuantiFERON TB-Gold In-Tube (QFT-GIT) in subjects at different stages of tuberculosis. A total of 16 individuals with remote LTBI and 23 with recent infection were studied; 15 controls unexposed to M. tuberculosis and 50 patients with active tuberculosis and 45 with cured tuberculosis were also analysed. The results indicated that subjects with remote LTBI showed significantly higher whole-blood interferon-gamma responses to M. tuberculosis latency antigen Rv2628 than did individuals with recent infection, active tuberculosis and controls (p<0.003), whereas no significant differences between these groups were found for other latency antigens tested (Rv2626c, Rv2627c, Rv2031c and Rv2032). The proportion of responders to Rv2628 was five-fold higher among QFT-GIT-positive-individuals with remote infection than among those with recently acquired infection. These data suggest that responses to M. tuberculosis latency antigen Rv2628 may associate with immune-mediated protection against tuberculosis. In contact-tracing investigations, these preliminary data may differentiate recent (positive QFT-GIT results without responses to Rv2628) from remote infection (positive to both tests).

The Impact of Preexisting or Acquired Kaposi Sarcoma Herpesvirus Infection in Kidney Transplant Recipients on Morbidity and Survival

The impact of preexisting or acquired Kaposi sarcoma herpesvirus (KSHV) infection in kidney transplant recipients was evaluated in a prospective study. Serum collected from kidney donors and recipients before transplantation were tested for antibodies against KSHV latent nuclear antigen. Three groups of recipients were defined: group A (KSHV+), group B (KSHV-, KSHV+ donor) and group C (donor and recipient KSHV-). Blood was collected from recipients, every 3 months for 3 years, for KSHV viremia (groups A and B), quantitative (group A) and qualitative serology (group B). Data of group C recipients were extracted from a French database. The prevalence of KSHV antibodies was 1.1% in donors and 3.2% in recipients. There were respectively 161, 64 and 4744 recipients in groups A, B and C. In group A, 13% developed Kaposi's sarcoma (KS). Age >53.5 years (p = 0.025) and black skin (p = 0.0054) were associated with KS development. In group B, three recipients developed clinical manifestations related to KSHV infection. There was no difference in terms of survival and graft loss between the three groups. In conclusion, although kidney recipients should be aware of the additional risk of KSHV morbidity, KSHV+ recipients should not be systematically excluded from kidney transplantation.