Search

From 2014 to 2016, the number of hepatitis E virus (HEV) infections in southern Switzerland increased dramatically and suggested food as a potential infection reservoir. We evaluated the effects of food control measures introduced to limit HEV infections, assessing anti-HEV IgG and IgM rates in blood donors before and after the implementation of food control measures in 2017. From 2012 to 2013, we screened 1283, and from 2017 to 2019, we screened 1447 donors for IgG and IgM antibodies. No statistically significant differences were detected for IgG (32.8% from 2012 to 2013 vs. 31.1% from 2017 to 2019, p = 0.337) or IgM rates (2.0% from 2012 to 2013 vs. 2.8% from 2017 to 2019, p = 0.21). Rural provenience and age > 66 are predictors for positive IgG serology. A total of 5.9% of 303 donors included in both groups lost IgG positivity. We also determined nucleic acid testing (NAT) rates after the introduction of this test in 2018, comparing 49,345 donation results from southern Switzerland with those of 625,559 Swiss donor controls, and only 9 NAT-positive donors were found from 2018 to 2023. The high HEV seroprevalence in southern Switzerland may depend on different food supply chains in rural and urban areas. Local preventive measures probably have a limited impact on blood HEV risk; thus, continuous NAT testing is recommended. [ABSTRACT FROM AUTHOR]

ABSTRACT Background In chronic HIV infection, antiretroviral therapy-induced normalization of CD[4.sup.+] T cell counts (immune reconstitution [IR]) is associated with a decreased incidence of opportunistic diseases. However, some individuals remain [...]

Background: Switzerland has made strides towards hepatitis C virus elimination, but as of 2019, elimination was not guaranteed. However, political interest in viral hepatitis has been increasing. We sought to develop a better understanding of Switzerland's progress towards HCV elimination and the profile of remaining HCV‐RNA‐positive patients. Methods: A previously described Markov model was updated with recent diagnosis and treatment data and run to generate new forecasts for HCV disease burden. Two scenarios were developed to evaluate HCV morbidity and mortality under the status quo and a scenario that achieves the Swiss Hepatitis Strategy Elimination targets. Next, an analysis was conducted to identify population segments bearing a high burden of disease, where future elimination efforts could be directed. Results: At the beginning of 2020, an estimated 32 100 viremic infections remained in Switzerland (0.37% viremic prevalence). Adult (≥18 years of age) permanent residents born abroad represented the largest subpopulation, accounting for 56% of HCV infections. Thirteen countries accounted for ≥60% of viremic infections amongst permanent residents born abroad, with most people currently residing in Zurich, Vaud, Geneva, Bern, Aargau and Ticino. Amongst Swiss‐born HCV‐RNA‐positive persons, two‐thirds had a history of IDU, corresponding to 33% of total infections. Conclusions: In Switzerland, extra efforts for diagnosis and linkage to care are warranted in foreign‐born populations and people with a history of drug use. Population‐level measures (eg increasing the number of providers, increase screening) can identify patients who may have otherwise fallen through the gaps or avoided care because of stigma. [ABSTRACT FROM AUTHOR]

Abstract Background Hepatitis B immune globulins (HBIG) in combination with nucleos(t)ide analogues (NA) are effectively used for the prevention of hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, associated treatment costs for HBIG are exceedingly high. Methods Fresh frozen plasma obtained from blood donors with high anti-HBs levels (hyperimmune plasma, HIP) containing at least 4,500 IU anti-HBs was used as alternative treatment for HBV recurrence prophylaxis post-LT. Results Twenty-one HBV-related LT recipients received HIP starting at transplantation, followed by long-term combination treatment with NA. Mean follow-up time was 4.5 years (range 0.5-12.6) and each patient received on average 8.2 HIP per year (range 5.8-11.4). Anti-HBs terminal elimination kinetic after HIP administration was 20.6 days (range 13.8-30.9), which is comparable to values reported for commercial HBIG products. All 21 patients remained free of HBV recurrence during follow-up and no transfusion-transmitted infection or other serious complication was observed. Seven patients developed reversible mild transfusion reactions. The cost for one HIP unit was US$140; average yearly HBIG treatment cost was US$1,148 per patient, as compared to US$25,000-100,000 for treatment with commercial HBIG. Conclusion The results of this study suggest that the use of HIP may be a useful and economical approach for the prevention of HBV recurrence post-LT if used in combination with NA. Additional prospective controlled studies in larger populations are needed to confirm these results.

Abstract Background Nodular regenerative hyperplasia (NRH) has been recently recognized as an emergent cause of liver disease in HIV-infected patients. NRH may cause non-cirrhotic portal hypertension with potentially severe consequences such as refractory ascites, variceal bleeding and hypersplenism. Obliteration of the small intrahepatic portal veins in association with prothrombotic disorders linked to HIV infection itself or anti-retroviral therapy seem to be the causes of NRH and thus the term HIV-associated obliterative portopathy has been proposed. Case Presentation Here we describe a case of a HIV-infected patient with biopsy-proven NRH and listed for liver transplantation (LT) because of refractory ascites and repeated upper gastrointestinal bleedings. A transjugular intrahepatic portosystemic shunt was placed as a bridge to LT and did not improve liver function. However, anticoagulant therapy with low-molecular-weight heparin (LMWH) was associated with rapid improvement in the liver condition and allowed to avoid LT in this patient. Conclusions Thus, this case underscores the relation between thrombophilia and HIV-associated NRH and emphasizes anticoagulant therapy as possible treatment.

Abstract Although the risk of transfusion-transmitted infections today is lower than ever, the supply of safe blood products remains subject to contamination with known and yet to be identified human pathogens. Only continuous improvement and implementation of donor selection, sensitive screening tests and effective inactivation procedures can ensure the elimination, or at least reduction, of the risk of acquiring transfusion transmitted infections. In addition, ongoing education and up-to-date information regarding infectious agents that are potentially transmitted via blood components is necessary to promote the reporting of adverse events, an important component of transfusion transmitted disease surveillance. Thus, the collaboration of all parties involved in transfusion medicine, including national haemovigilance systems, is crucial for protecting a secure blood product supply from known and emerging blood-borne pathogens.

Abstract The assessment of cellular anti-viral immunity is often hampered by the limited availability of adequate samples, especially when attempting simultaneous, high-resolution determination of T cell responses against multiple viral infections. Thus, the development of assay systems, which optimize cell usage, while still allowing for the detailed determination of breadth and magnitude of virus-specific cytotoxic T lymphocyte (CTL) responses, is urgently needed. This study provides an up-to-date listing of currently known, well-defined viral CTL epitopes for HIV, EBV, CMV, HCV and HBV and describes an approach that overcomes some of the above limitations through the use of peptide matrices of optimally defined viral CTL epitopes in combination with anti-CD3 in vitro T cell expansion and re-use of cells from negative ELISpot wells. The data show that, when compared to direct ex vivo cell preparations, antigen-unspecific in vitro T cell expansion maintains the breadth of detectable T cell responses and demonstrates that harvesting cells from negative ELISpot wells for re-use in subsequent ELISpot assays (RecycleSpot), further maximized the use of available cells. Furthermore when combining T cell expansion and RecycleSpot with the use of rationally designed peptide matrices, antiviral immunity against more than 400 different CTL epitopes from five different viruses can be reproducibly assessed from samples of less than 10 milliliters of blood without compromising information on the breadth and magnitude of these responses. Together, these data support an approach that facilitates the assessment of cellular immunity against multiple viral co-infections in settings where sample availability is severely limited.

Introduction: In the last years, nonalcoholic steatohepatitis (NASH) has become a leading indication for liver transplant (LT). After transplant, both recurrent and de novo nonalcoholic fatty liver disease (NAFLD) can be commonly diagnosed. However, dedicated surveillance programs for patients with pre- or post-transplant NAFLD are not available. Areas covered: Patients waiting for LT for NASH show specific peculiarities and would deserve targeted stratification of mortality risk. Obesity, hyperlipidemia, and diabetes mellitus can be often found after transplant. These conditions, together with immunosuppressive regimen, make LT recipients a high-risk population for both recurrent and de novo NAFLD. Development of fatty liver disease after LT has a relevant impact on both morbidity and mortality. Expert commentary: A targeted stratification of neoplastic and cardiovascular risk for patients with NASH waiting for LT would be mandatory. In both pre- and post-transplant period, NAFLD should be considered not only a liver disease but also a cardiovascular risk factor. Patients within Transplant Program, especially those with known metabolic risk factors, should be followed with personalized diagnostic and life-style interventions before and after LT. [ABSTRACT FROM AUTHOR]

Catalyzed by the concerns over the growing public health and economic burden of Hepatitis C virus (HCV) in Switzerland, a diverse group of experts and patient representatives came together in 2014 to develop the Swiss Hepatitis Strategy, setting targets for the elimination of viral hepatitis in Switzerland by 2030. Previous studies have reported the estimated number of chronic HCV infections and forecasted burden of disease given different intervention strategies. However, given new prevalence data by the Swiss Federal Office of Public Health, which decreased total infections by about half, an updated analysis is warranted. We aimed to provide an updated viremic prevalence estimate for Switzerland and evaluate the impact on forecasted liver related morbidity and mortality of an ‘inaction’ scenario and intervention scenarios to achieve the Global Health Sector Strategy for Viral Hepatitis and Swiss Hepatitis Strategy goals by 2030. A Markov disease-progression model was used to calculate the present and future burden of HCV infection by disease stage according to these different strategies. In 2017, there were an estimated 36,800 (95% UI: 26,900–39,200) viremic infections in Switzerland. Given the current standard of care, total viremic infections are expected to decline by 45%, while cases of decompensated cirrhosis, hepatocellular carcinoma, and liver-related deaths will decrease by 20%. If treatment and diagnosis efforts were to cease in 2018, late stage HCV-related morbidity and mortality would increase by 90–100% by 2030. Increasing treatment and diagnosis to achieve the Global Health Sector Strategy or Swiss Hepatitis Strategy goals by 2030, will reduce the number of chronic infections to less than 13,000 and 4,000, respectively. Although the HCV epidemic is declining in Switzerland, efforts to expand diagnosis and treatment are needed to achieve elimination by 2030. [ABSTRACT FROM AUTHOR]

Abstract: Background: Autochthonous hepatitis E is increasingly recognized as zoonotic infection in western countries. Serological assays have varying sensitivity and specificity. Methods: We implemented molecular testing to identify and characterize acute hepatitis E acquired in Switzerland. Results: Ninety‐three cases of mostly symptomatic acute hepatitis E acquired in Switzerland were documented by PCR between November 2011 and December 2016. Median HEV RNA was 7.5 x 104 IU/mL (range, 5.3 to 4.7 x 107 IU/mL). HEV genotyping was successful in 78 patients, revealing genotype 3 in 75 and genotype 4 in three patients. Phylogenetic analyses revealed a few limited geographical and temporal clusters. Of the 91 patients with available anti‐HEV IgM serology, four were negative; three of these were also IgG‐negative, likely as a result of immunosuppression, and one was IgG‐positive, a constellation compatible with HEV reinfection. Median age of the patients was 58 years (range, 20‐80 years); 71 (76.3%) were men and 49 of these (69.0%) were ≥ 50 years old. The clinical course was particularly severe in patients with underlying chronic liver disease, with fatal outcome in two patients. Six patients (6.5%) presented with neuralgic amyotrophy. Conclusions: Nucleic acid‐based diagnosis reveals HEV as a relevant cause of acute hepatitis in Switzerland. Middle‐aged and elderly men constitute the majority of symptomatic patients. Testing for HEV should be included early in the diagnostic workup of acute hepatitis and of neuralgic amyotrophy, a typical extrahepatic manifestation of HEV genotype 3 infection. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) genotypes can influence treatment outcome in HBV-monoinfected and human immunodeficiency virus (HIV)/HBV-coinfected patients. Tenofovir disoproxil fumarate (TDF) plays a pivotal role in antiretroviral therapy (ART) of HIV/HBV-coinfected patients. The influence of HBV genotypes on the response to antiviral drugs, particularly TDF, is poorly understood. Methods: HIV/HBV-co-infected participants with detectable HBV DNA prior to TDF therapy were selected from the Swiss HIV Cohort Study. HBV genotypes were identified and resistance testing was performed prior to antiviral therapy, and in patients with delayed treatment response (>6 months). The efficacy of TDF to suppress HBV (HBV DNA <20 IU/mL) and the influence of HBV genotypes were determined. Results: 143 HIV/HBV-coinfected participants with detectable HBV DNA were identified. The predominant HBV genotypes were A (82 patients, 57 %); and D (35 patients, 24 %); 20 patients (14 %) were infected with multiple genotypes (3 % A + D and 11 % A + G); and genotypes B, C and E were each present in two patients (1 %). TDF completely suppressed HBV DNA in 131 patients (92 %) within 6 months; and in 12 patients (8 %), HBV DNA suppression was delayed. No HBV resistance mutations to TDF were found in patients with delayed response, but all were infected with HBV genotype A (among these, 5 patients with genotype A + G), and all had previously been exposed to lamivudine. Conclusion: In HIV/HBV-coinfected patients, infection with multiple HBV genotypes was more frequent than previously reported. The large majority of patients had an undetectable HBV viral load at six months of TDF-containing ART. In patients without viral suppression, no TDF-related resistance mutations were found. The role of specific genotypes and prior lamivudine treatment in the delayed response to TDF warrant further investigation. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis C virus infection is a major cause of liver disease in Switzerland and carries a significant cost burden. Currently, only conservative strategies are in place to mitigate the burden of hepatitis C in Switzerland. This study expands on previously described modeling efforts to explore the impact of: no treatment, and treatment to reduce HCC and mortality. Furthermore, the costs associated with untreated HCV were modeled. Methods: Hepatitis C disease progression and mortality were modeled. Baseline historical assumptions were collected from the literature and expert interviews and strategies were developed to show the impact of different levels of intervention (improved drug cure rates, treatment and diagnosis) until 2030. Results: Under the historical standard of care, the number of advanced stage cases was projected to increase until 2030, at which point the annual economic burden of untreated viremic infections was projected to reach €96.8 (95% Uncertainty Interval: €36 – €232) million. Scenarios to reduce HCV liver-related mortality by 90% by 2030 required treatment of 4,190 ≥F2 or 3,200 ≥F3 patients annually by 2018 using antivirals with a 95% efficacy rate. Delaying the implementation of these scenarios by 2 or 5 years reduced the impact on mortality to 75% and 57%, respectively. Conclusions: With today’s treatment efficacy and uptake rates, hepatitis C disease burden is expected to increase through 2030. A substantial reduction in disease burden can be achieved by means of both higher efficacy drugs and increased treatment uptake. However, these efforts cannot be undertaken without a simultaneous effort to diagnose more infections. [ABSTRACT FROM AUTHOR]

Background & Aims: The immune impairment characterizing chronic hepatitis B (cHBV) infection is thought to be the consequence of persistent exposure to viral antigens. However, the immune correlates of different clinical stages of cHBV and their relation with different levels of HBsAg have not been investigated. The aim of the present study was to evaluate the relationship between HBV-specific T cells response and the degree of in vivo HBV control and HBsAg serum levels in HBeAg-HBeAb+ cHBV. Methods: Peripheral blood mononuclear cells from 42 patients with different clinical profiles (treatment-suppressed, inactive carriers and active hepatitis) of cHBV, 6 patients with resolved HBV infection and 10 HBV-uninfected individuals were tested with overlapping peptides spanning the entire HBV proteome. The frequency and magnitude of HBV-specific T cell responses was assessed by IFNγ ELISPOT assay. Serum HBsAg was quantified with a chemiluminescent immunoassay. Results: The total breadth and magnitude of HBV-specific T cell responses did not differ significantly between the four groups. However, inactive carriers targeted preferentially the core region. In untreated patients, the breadth of the anti-core specific T cell response was inversely correlated with serum HBsAg concentrations as well as HBV-DNA and ALT levels and was significantly different in patients with HBsAg levels either above or below 1000 IU/mL. The same inverse association between anti-core T cell response and HBsAg levels was found in treated patients. Conclusions: Different clinical outcomes of cHBV infection are associated with the magnitude, breadth and specificity of the HBV-specific T cell response. Especially, robust anti-core T cell responses were found in the presence of reduced HBsAg serum levels, suggesting that core-specific T cell responses can mediate a protective effect on HBV control. [ABSTRACT FROM AUTHOR]

Background: Nodular regenerative hyperplasia (NRH) has been recently recognized as an emergent cause of liver disease in HIV-infected patients. NRH may cause non-cirrhotic portal hypertension with potentially severe consequences such as refractory ascites, variceal bleeding and hypersplenism. Obliteration of the small intrahepatic portal veins in association with prothrombotic disorders linked to HIV infection itself or anti-retroviral therapy seem to be the causes of NRH and thus the term HIV-associated obliterative portopathy has been proposed. Case Presentation: Here we describe a case of a HIV-infected patient with biopsy-proven NRH and listed for liver transplantation (LT) because of refractory ascites and repeated upper gastrointestinal bleedings. A transjugular intrahepatic portosystemic shunt was placed as a bridge to LT and did not improve liver function. However, anticoagulant therapy with low-molecular-weight heparin (LMWH) was associated with rapid improvement in the liver condition and allowed to avoid LT in this patient. Conclusions: Thus, this case underscores the relation between thrombophilia and HIV-associated NRH and emphasizes anticoagulant therapy as possible treatment. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B immune globulins (HBIG) in combination with nucleos(t)ide analogues (NA) are effectively used for the prevention of hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, associated treatment costs for HBIG are exceedingly high. Methods: Fresh frozen plasma obtained from blood donors with high anti-HBs levels (hyperimmune plasma, HIP) containing at least 4,500 IU anti-HBs was used as alternative treatment for HBV recurrence prophylaxis post-LT. Results: Twenty-one HBV-related LT recipients received HIP starting at transplantation, followed by long-term combination treatment with NA. Mean follow-up time was 4.5 years (range 0.5-12.6) and each patient received on average 8.2 HIP per year (range 5.8-11.4). Anti-HBs terminal elimination kinetic after HIP administration was 20.6 days (range 13.8-30.9), which is comparable to values reported for commercial HBIG products. All 21 patients remained free of HBV recurrence during follow-up and no transfusion-transmitted infection or other serious complication was observed. Seven patients developed reversible mild transfusion reactions. The cost for one HIP unit was US$140; average yearly HBIG treatment cost was US$1,148 per patient, as compared to US$25,000-100,000 for treatment with commercial HBIG. Conclusion: The results of this study suggest that the use of HIP may be a useful and economical approach for the prevention of HBV recurrence post-LT if used in combination with NA. Additional prospective controlled studies in larger populations are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Background: Nodular regenerative hyperplasia (NRH) has been recently recognized as an emergent cause of liver disease in HIV-infected patients. NRH may cause non-cirrhotic portal hypertension with potentially severe consequences such as refractory ascites, variceal bleeding and hypersplenism. Obliteration of the small intrahepatic portal veins in association with prothrombotic disorders linked to HIV infection itself or anti-retroviral therapy seem to be the causes of NRH and thus the term HIV-associated obliterative portopathy has been proposed. Case Presentation: Here we describe a case of a HIV-infected patient with biopsy-proven NRH and listed for liver transplantation (LT) because of refractory ascites and repeated upper gastrointestinal bleedings. A transjugular intrahepatic portosystemic shunt was placed as a bridge to LT and did not improve liver function. However, anticoagulant therapy with low-molecular-weight heparin (LMWH) was associated with rapid improvement in the liver condition and allowed to avoid LT in this patient. Conclusions: Thus, this case underscores the relation between thrombophilia and HIV-associated NRH and emphasizes anticoagulant therapy as possible treatment. [ABSTRACT FROM AUTHOR]

Background In chronic HIV infection, antiretroviral therapy-induced normalization of CD4+ T cell counts (immune reconstitution [IR]) is associated with a decreased incidence of opportunistic diseases. However, some individuals remain at risk for opportunistic diseases despite prolonged normalization of CD4+ T cell counts. Deficient Epstein-Barr virus (EBV)-specific CD4+ T cell function may explain the occurrence of EBV-associated opportunistic malignancy--such as primary central nervous system (PCNS) lymphoma--despite recovery of absolute CD4+ T cell counts. Methods and Findings Absolute CD4+ T cell counts and EBV-specific CD4+ T cell-dependent interferon-γ production were assessed in six HIV-positive individuals prior to development of PCNS lymphoma ("cases"), and these values were compared with those in 16 HIV-infected matched participants with no sign of EBV-associated pathology ("matched controls") and 11 nonmatched HIV-negative blood donors. Half of the PCNS lymphoma patients fulfilled IR criteria (defined here as CD4+ T cell counts ≥500/µl blood). EBV-specific CD4+ T cells were assessed 0.5-4.7 y prior to diagnosis of lymphoma. In 0/6 cases versus 13/16 matched controls an EBV-specific CD4+ T cell response was detected (p=0.007; confidence interval for odds ratio [0-0.40]). PCNS lymphoma patients also differed with regards to this response significantly from HIV-negative blood donors (p < 0.001, confidence interval for odds ratio [0-0.14]), but there was no evidence for a difference between HIV-negative participants and the HIV-positive matched controls (p=0.47). Conclusions Irrespective of absolute CD4+ T cell counts, HIV-positive patients who subsequently developed PCNS lymphoma lacked EBV-specific CD4+ T cell function. Larger, ideally prospective studies are needed to confirm these preliminary data, and clarify the impact of pathogen-specific versus surrogate marker-based assessment of IR on clinical outcome. [ABSTRACT FROM AUTHOR]

Although the risk of transfusion-transmitted infections today is lower than ever, the supply of safe blood products remains subject to contamination with known and yet to be identified human pathogens. Only continuous improvement and implementation of donor selection, sensitive screening tests and effective inactivation procedures can ensure the elimination, or at least reduction, of the risk of acquiring transfusion transmitted infections. In addition, ongoing education and up-to-date information regarding infectious agents that are potentially transmitted via blood components is necessary to promote the reporting of adverse events, an important component of transfusion transmitted disease surveillance. Thus, the collaboration of all parties involved in transfusion medicine, including national haemovigilance systems, is crucial for protecting a secure blood product supply from known and emerging blood-borne pathogens. [ABSTRACT FROM AUTHOR]

The assessment of cellular anti-viral immunity is often hampered by the limited availability of adequate samples, especially when attempting simultaneous, high-resolution determination of T cell responses against multiple viral infections. Thus, the development of assay systems, which optimize cell usage, while still allowing for the detailed determination of breadth and magnitude of virusspecific cytotoxic T lymphocyte (CTL) responses, is urgently needed. This study provides an upto-date listing of currently known, well-defined viral CTL epitopes for HIV, EBV, CMV, HCV and HBV and describes an approach that overcomes some of the above limitations through the use of peptide matrices of optimally defined viral CTL epitopes in combination with anti-CD3 in vitro T cell expansion and re-use of cells from negative ELISpot wells. The data show that, when compared to direct ex vivo cell preparations, antigen-unspecific in vitro T cell expansion maintains the breadth of detectable T cell responses and demonstrates that harvesting cells from negative ELISpot wells for re-use in subsequent ELISpot assays (RecycleSpot), further maximized the use of available cells. Furthermore when combining T cell expansion and RecycleSpot with the use of rationally designed peptide matrices, antiviral immunity against more than 400 different CTL epitopes from five different viruses can be reproducibly assessed from samples of less than 10 milliliters of blood without compromising information on the breadth and magnitude of these responses. Together, these data support an approach that facilitates the assessment of cellular immunity against multiple viral co-infections in settings where sample availability is severely limited. [ABSTRACT FROM AUTHOR]

After an acute hepatitis E (HEV) outbreak in Southern Switzerland, in January 2017 the local public health authorities started an active program of food chain control and public education. In this retrospective study, we analysed all laboratory-confirmed acute cases of HEV infection diagnosed between 2014 and 2020. In the period before the public health intervention, the number of cases increased steadily from 2014 (4 of 40 tests, 10%) reaching a peak in the last quarter of 2016 (42 of 285 tests, 14.7 %). Afterwards, the number of positive cases decreased steadily, reaching its lowest value (0.3%) in the second quarter of 2019. There was a statistically significant difference between the frequency of positive cases and period of testing, i.e., before and after the introduction of the public health interventions. Our study shows that active public health measures to control sausages containing raw pork liver can reduce the prevalence of HEV infection. [ABSTRACT FROM AUTHOR]

The cellular immunity against Kaposi's sarcoma-associated herpesvirus (KSHV) is poorly characterized and has not been compared to T-cell responses against other human herpesviruses. Here, novel and dominant targets of KSHV-specific cellular immunity are identified and compared to T cells specific for lytic and latent antigens in a second human gammaherpesvirus, Epstein-Barr virus. The data identify a novel HLA-B57- and HLA-B58-restricted epitope in the Orf57 protein and show consistently close parallels in immune phenotypes and functional response patterns between cells targeting lytic or latent KSHV- and EBV-encoded antigens, suggesting common mechanisms in the induction of these responses. [ABSTRACT FROM AUTHOR]