Update of the global distribution of human gammaherpesvirus 8 genotypes.

Human gammaherpesvirus 8 (HHV-8) consists of six major clades (A-F) based on the genetic sequence of the open reading frame (ORF)-K1. There are a few conflicting reports regarding the global distribution of the different HHV-8 genotypes. This study aimed to determine the global distribution of the different HHV-8 genotypes based on phylogenetic analysis of the ORF-K1 coding region using sequences published in the GenBank during 1997-2020 and construct a phylogenetic tree using the maximum likelihood algorithm with the GTR + I + G nucleotide substitution model. A total of 550 sequences from 38 countries/origins were analysed in this study. Genotypes A and C had similar global distributions and were prevalent in Africa and Europe. Genotype B was prevalent in Africa. Of the rare genotypes, genotype D was reported in East Asia and Oceania and genotype E in South America, while genotype F was prevalent in Africa. The highest genotypic diversity was reported in the American continent, with Brazil housing five HHV-8 genotypes (A, B, C, E, and F). In this study, we present update of the global distribution of HHV-8 genotypes, providing a basis for future epidemiological and evolutionary studies of HHV-8.

Developing new ceramide analogs and identifying novel sphingolipid-controlled genes against a virus-associated lymphoma.

Primary effusion lymphoma (PEL) is an aggressive malignancy with poor prognosis even under chemotherapy. Kaposi sarcoma-associated herpesvirus (KSHV), one of the human oncogenic viruses, is the principal causative agent. Currently, there is no specific treatment for PEL; therefore, developing new therapies is of great importance. Sphingolipid metabolism plays an important role in determining the fate of tumor cells. Our previous studies have demonstrated that there is a correlation between sphingolipid metabolism and KSHV+ tumor cell survival. To further develop sphingolipid metabolism-targeted therapy, after screening a series of newly synthesized ceramide analogs, here, we have identified compounds with effective anti-PEL activity. These compounds induce significant PEL apoptosis, cell-cycle arrest, and intracellular ceramide production through regulation of ceramide synthesizing or ceramide metabolizing enzymes and dramatically suppress tumor progression without visible toxicity in vivo. These new compounds also increase viral lytic gene expression in PEL cells. Our comparative transcriptomic analysis revealed their mechanisms of action for inducing PEL cell death and identified a subset of novel cellular genes, including AURKA and CDCA3, controlled by sphingolipid metabolism, and required for PEL survival with functional validation. These data provide the framework for the development of promising sphingolipid-based therapies against this virus-associated malignancy.

Sarcoma de Kaposi epidémico en África Subsahariana / Epidemic Kaposi sarcoma in Sub-Saharan Africa

El sarcoma de Kaposi se ha convertido en uno de los tumores más prevalentes en África tras la epidemia de VIH, que afecta de una manera similar a hombres y mujeres. El retraso diagnóstico y el limitado acceso a tratamiento antirretroviral o quimioterapia condicionan el pronóstico de los pacientes que lo padecen. En este artículo se realiza una revisión sobre la referida enfermedad, con el objetivo de describir sus aspectos más relevantes en los últimos años en África, como son su epidemiología, caractéristicas clínicas y opciones terapéuticas existentes. Este tumor es provocado por la infección por virus herpes humano tipo 8, que resulta más prevalente en las zonas rurales del continente africano. Se postula la transmisión a través de la saliva como la vía más importante de contagio en África. La inmunodepresión que causa el VIH favorece el efecto oncogénico del virus. La forma epidémica de SK se manifiesta inicialmente como lesiones hiperpigmentadas o violáceas en la piel, que pueden extenderse a linfáticos o mucosas y a nivel sistémico, principalmente a pulmón o aparato digestivo. El síndrome de reconstitución inmune sistémica puede complicar la evolución del paciente. El inicio temprano de la terapia antirretroviral resulta imprescindible. Además, el pronóstico de los pacientes mejora con la suma de tratamiento quimioterápico con doxorrubicina, vincristina, etopóxido o bleomicina principalmente(AU)

Kaposi sarcoma (KS) has become one of the most prevalent tumors in Africa after the HIV epidemic. KS affects both men and women. Diagnostic delay and limited access to antiretroviral treatment or chemotherapy have an impact on the prognosis of KS patients. A review was conducted about KS with the purpose of describing its most outstanding characteristics in recent years in Africa, such as its epidemiology, clinical features, and existing therapeutic options. This tumor is caused by infection with human herpesvirus 8, which is more prevalent in rural areas of the African continent. Transmission via saliva was found to be the most important transmission route in Africa. HIV-related immunosuppression fosters the oncogenic effect of the virus. The epidemic form of KS initially presents as hyperpigmented or violet-colored skin lesions which may extend to lymph nodes or mucosae, or systemically, mainly to the lungs or the digestive tract. Systemic immune reconstitution syndrome may complicate the patient's evolution. Early start of antiretroviral therapy is indispensable. Additionally, prognosis improves with chemotherapy with doxorubicin, vincristine, etoposide or bleomycin, mainly(AU)

No detectable human herpesvirus-8 oral shedding in seronegative-healthy, immunocompetent individuals from non-endemic regions for Kaposi's sarcoma: A pilot study.

AIM: Saliva can play an important role in human herpesvirus-8 (HHV-8) transmission in endemic regions for Kaposi's sarcoma (KS). Little is known about HHV-8 oral shedding in immunocompetent individuals from non-endemic regions for KS. METHODS: We conducted a prospective study of HHV-8 salivary excretion among 59 healthy, immunocompetent individuals from São Paulo, Brazil, followed up weekly for 4 months, resulting in 16 saliva samples from each participant. Antibodies to HHV-8 latency-associated nuclear antigen (LANA) and lytic-phase antigens were investigated with immunofluorescence assays (IFA). HHV-8 DNA detection was performed using real-time polymerase chain reaction (PCR). RESULTS: All 59 individuals were seronegative to LANA and lytic antibodies. HHV-8 DNA was undetectable in saliva samples in 100% of the participants, totaling 944 samples and being consistently negative during the different periods of sampling, which lasted approximately 120 days. No sequences of HHV-8 DNA were detected in the saliva samples of healthy, immunocompetent adults by using real-time PCR, with the resulting data being consistent with IFA-based serological tests. CONCLUSIONS: Unlike other herpesviruses, HHV-8 is not excreted in the saliva of healthy individuals from non-endemic regions for KS.

NF-kappaB signaling modulation by EBV and KSHV.

The nuclear factor (NF)-kappaB signaling pathway is pivotal for immune system function. Not surprisingly, pathogenic microorganisms have developed strategies to subvert it. Two examples are Epstein-Barr virus (EBV) and Kaposi sarcoma herpesvirus (KSHV), oncogenic gammaherpesviruses that establish a lifelong latent infection in their human hosts. The modulation of NF-kappaB signaling by EBV and KSHV is not only important for viral infection, but also contributes to the development of malignant neoplasia. This review explores the current knowledge of NF-kappaB modulation by EBV and KSHV, focusing on connections between viral biology and human carcinogenesis.

Infection with human herpesvirus type 8 and human T-cell leukaemia virus type 1 among individuals participating in a case-control study in Havana City, Cuba.

Infection with human herpesvirus type 8 and with human T-cell leukaemia virus type-1 shows strong geographic variations. We conducted this study to assess prevalence and risk factors for human herpesvirus type 8 infection in Havana City, Cuba. Information and residual serum samples already collected for a hospital based case-control study were used. A total of 379 individuals (267 males and 112 females; median age=63 years) were evaluated. Antibodies to the lytic antigen of human herpesvirus type 8 were detected by using an immunofluorescence assay, while human T-cell leukaemia virus type-1 serology was performed by means of an ELISA test (alpha Biotech). Overall, 64 subjects (16.9%, 95% confidence interval: 13.1-20.0) were positive for human herpesvirus type 8 antibodies. Human herpesvirus type 8 seroprevalence significantly increased with age (odds ratio=1.9 for >/=65 vs <55 years), and was twice as frequent in blacks than in whites. No association emerged with gender, socio-economic indicators, family size, history of sexually transmitted disease, sexual behaviour. Overall, 16 persons had anti-human T-cell leukaemia virus type-1 antibodies (4.2%, 95% confidence interval: 2.2-6.4). No relationship emerged between human T-cell leukaemia virus type-1 and human herpesvirus type 8 serostatus. The study findings indicate that human herpesvirus type 8 infection is relatively common in Havana City, Cuba, suggesting that Cuba may represent an intermediate endemical area. Sexual transmission does not seem to play a major role in the spread human herpesvirus type 8 infection.

Human herpesvirus 8 and oral health care: an update.

OBJECTIVE: The purpose of this report was to review the current literature on human herpesvirus 8 (HHV-8) with particular attention to the aspects of interest for dental health care workers. MATERIAL AND METHODS: The authors searched original research and review articles on specific aspects of HHV-8 infection, including virology, epidemiology, transmission, diagnosis, natural history, therapy, and oral aspects. The relevant material was evaluated and reviewed. RESULTS: HHV-8 is a recently discovered DNA virus that is present throughout the world but with major geographic variation. In the Western world, the virus, transmitted mainly by means of sexual contact, is strongly associated with Kaposi's sarcoma and body cavity-based lymphoma and more controversially with multiple myeloma and non-neoplastic disorders. There is no specific effective treatment, but human immunodeficiency virus protease inhibitors may play an indirect role in the clearance of HHV-8 DNA from peripheral blood mononuclear cells of patients infected with human immunodeficiency virus. HHV-8 DNA is present in saliva, but as yet, there are no documented instances of nosocomial transmission to health care workers. The prevalence of HHV-8 among dental health care workers is probably similar to that in the general population. CONCLUSION: HHV-8 does not appear to be ubiquitous in most populations, particularly in western Europe and the United States, where it may be restricted to a population at risk of having Kaposi's sarcoma develop (men infected with human immunodeficiency virus and patients who are iatrogenically immunosuppressed). Most serologic studies suggest a global HHV-8 seroprevalence of 2% to 10% and show that the virus may be under immunologic control in people who are healthy but infected with HHV-8. Also, HHV-8 certainly has the means to overcome cellular control and immune responses and thus predispose to malignancy. To date, there are no data to suggest that health care staff members are at particular risk of HHV-8 acquisition through occupational routes.

Human herpes virus 8 and kaposi's sarcoma: A review

Kaposi's Sarcoma (KS) was first described one century ago as a disease occurring in elderly men manifested as an indolent cutaneous form. After the onset of human immunodeficiency virus type I (HIV-1) infection, KS became epidemic which, in association with HIV, presented as an aggressive, systemic disease. Recently, the recognition that a novel human herpes virus-8 (HHV-8) was highly prevalent among KS patients provided strong evidence to indicate that HHV-8 was the etiology of KS. The pathogenesis of KS in AIDS patients is still controversial, but there is evidence suggesting that KS is a cytokine-mediated disease, and that increased levels of inflammatory cytokines in AIDS patients were responsible for the aggressive pattern of disease seen in such patients. The recently developed serological assays for detection of HHV-8 antibodies have made possible a better understanding of the prevalence of HHV-8 in different populations, and this has allowed a deeper understanding of HIV-8 epidemiology.

Immune dysfunction and the pathogenesis of AIDS-associated non-Hodgkin's lymphoma.

Much has been learned about how HIV-induced immune dysfunction contributes to B cell hyperactivation, and potentially, to the pathogenesis of AIDS-lymphoma. However, further studies are needed to fully understand how HIV infection and immune dysfunction promote B cell hyperactivation and the development/growth of AIDS-lymphoma. In particular, studies are needed to define the role of HHV8 vIL6, IL6 receptor-expression, and lymphocyte surface stimulatory molecules, in promoting B cell hyperactivation or lymphoma cell growth.