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1.
J Med Virol ; 96(5): e29684, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38773828

RESUMO

Kaposi's sarcoma (KS) may derive from Kaposi's sarcoma herpesvirus (KSHV)-infected human mesenchymal stem cells (hMSCs) that migrate to sites characterized by inflammation and angiogenesis, promoting the initiation of KS. By analyzing the RNA sequences of KSHV-infected primary hMSCs, we have identified specific cell subpopulations, mechanisms, and conditions involved in the initial stages of KSHV-induced transformation and reprogramming of hMSCs into KS progenitor cells. Under proangiogenic environmental conditions, KSHV can reprogram hMSCs to exhibit gene expression profiles more similar to KS tumors, activating cell cycle progression, cytokine signaling pathways, endothelial differentiation, and upregulating KSHV oncogenes indicating the involvement of KSHV infection in inducing the mesenchymal-to-endothelial (MEndT) transition of hMSCs. This finding underscores the significance of this condition in facilitating KSHV-induced proliferation and reprogramming of hMSCs towards MEndT and closer to KS gene expression profiles, providing further evidence of these cell subpopulations as precursors of KS cells that thrive in a proangiogenic environment.


Assuntos
Herpesvirus Humano 8 , Células-Tronco Mesenquimais , Sarcoma de Kaposi , Humanos , Herpesvirus Humano 8/fisiologia , Herpesvirus Humano 8/genética , Sarcoma de Kaposi/virologia , Células-Tronco Mesenquimais/virologia , Diferenciação Celular , Células Cultivadas , Perfilação da Expressão Gênica , Proliferação de Células
4.
Eur Rev Med Pharmacol Sci ; 28(7): 2929-2942, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38639530

RESUMO

Human immunodeficiency virus (HIV) infection has historically been related to the development of specific cancers, some of which are so closely linked to the infection, such as Kaposi's Sarcoma (KS), that they have earned the name Acquired Immuno-Deficiency Syndrome (AIDS)-defining cancers (ADCs). While the development of antiretroviral therapy (ART) has decreased the incidence of AIDS-defining cancers, the resulting aging of people living with HIV (PLWH) highlighted an increased occurrence of other forms of cancer. At the "Gaetano Martino" hospital in Messina, we developed a multidisciplinary approach by creating a bridge between the Oncology Unit and the Infectious Diseases Unit to carry out screening and a more rapid diagnostic and therapeutic journey for cancers in PLWH. The goal is to improve the diagnosis of various types of cancer by involving other professionals, such as gastroenterologists and gynecologists, to ensure faster access to treatment and, therefore, a greater chance of survival. In addition, our multidisciplinary approach has also included vaccine screening, offered by the "Gaetano Martino" hospital and useful for preventing the development of specific forms of cancer in the entire population and particularly in PLWH.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Neoplasias , Sarcoma de Kaposi , Humanos , Detecção Precoce de Câncer , Fatores de Risco , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Sarcoma de Kaposi/epidemiologia , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Hospitais
5.
Int J Mol Sci ; 25(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38612584

RESUMO

Human herpesvirus 8 (HHV8)-associated diseases include Kaposi sarcoma (KS), multicentric Castleman disease (MCD), germinotropic lymphoproliferative disorder (GLPD), Kaposi sarcoma inflammatory cytokine syndrome (KICS), HHV8-positive diffuse large B-cell lymphoma (HHV8+ DLBCL), primary effusion lymphoma (PEL), and extra-cavitary PEL (ECPEL). We report the case of a human immunodeficiency virus (HIV)-negative male treated for cutaneous KS, who developed generalized lymphadenopathy, hepatosplenomegaly, pleural and abdominal effusions, renal insufficiency, and pancytopenia. The excised lymph node showed features of concomitant involvement by micro-KS and MCD, with aggregates of HHV8+, Epstein Barr virus (EBV)-negative, IgM+, and lambda+ plasmablasts reminiscent of microlymphoma. Molecular investigations revealed a somatically hypermutated (SHM) monoclonal rearrangement of the immunoglobulin heavy chain (IGH), accounting for 4% of the B-cell population of the lymph node. Mutational analyses identified a pathogenic variant of KMT2D and variants of unknown significance in KMT2D, FOXO1, ARID1A, and KMT2A. The patient died shortly after surgery. The histological features (HHV8+, EBV-, IgM+, Lambda+, MCD+), integrated with the molecular findings (monoclonal IGH, SHM+, KMT2D mutated), supported the diagnosis of a monoclonal HHV8+ microlymphoma, with features intermediate between an incipient HHV8+ DLBCL and an EBV-negative ECPEL highlighting the challenges in the accurate classification of HHV8-driven lymphoid proliferations.


Assuntos
Hiperplasia do Linfonodo Gigante , Infecções por Vírus Epstein-Barr , Infecções por HIV , Herpesvirus Humano 8 , Sarcoma de Kaposi , Masculino , Humanos , Herpesvirus Humano 8/genética , Sarcoma de Kaposi/genética , Herpesvirus Humano 4 , Infecções por HIV/complicações , Imunoglobulina M
7.
Cell Host Microbe ; 32(5): 755-767.e4, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38653242

RESUMO

Kaposi sarcoma (KS) is the most common cancer in persons living with HIV. It is caused by KS-associated herpesvirus (KSHV). There exists no animal model for KS. Pronuclear injection of the 170,000-bp viral genome induces early-onset, aggressive angiosarcoma in transgenic mice. The tumors are histopathologically indistinguishable from human KS. As in human KS, all tumor cells express the viral latency-associated nuclear antigen (LANA). The tumors transcribe most viral genes, whereas endothelial cells in other organs only transcribe the viral latent genes. The tumor cells are of endothelial lineage and exhibit the same molecular pattern of pathway activation as KS, namely phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR, interleukin-10 (IL-10), and vascular endothelial growth factor (VEGF). The KSHV-induced tumors are more aggressive than Ha-ras-induced angiosarcomas. Overall survival is increased by prophylactic ganciclovir. Thus, whole-virus KSHV-transgenic mice represent an accurate model for KS and open the door for the genetic dissection of KS pathogenesis and evaluation of therapies, including vaccines.


Assuntos
Modelos Animais de Doenças , Hemangiossarcoma , Herpesvirus Humano 8 , Camundongos Transgênicos , Sarcoma de Kaposi , Animais , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/patogenicidade , Camundongos , Hemangiossarcoma/virologia , Hemangiossarcoma/genética , Hemangiossarcoma/patologia , Sarcoma de Kaposi/virologia , Sarcoma de Kaposi/patologia , Genoma Viral , Humanos , Antígenos Virais/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Ganciclovir/uso terapêutico , Ganciclovir/farmacologia , Interleucina-10/genética
8.
Medicine (Baltimore) ; 103(14): e37706, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579031

RESUMO

RATIONALE: Kaposiform hemangioendothelioma is an aggressive vascular tumor that is often associated with life-threatening coagulopathies and Kasabach-Merritt phenomenon. Pathologic biopsies can provide a good basis for diagnosis and treatment. Therapy with srolimus combined with glucocorticoids may offer patients a favorable prognosis. PATIENT CONCERNS: A large purplish-red mass on the knee of a child with extremely progressive thrombocytopenia and refractory coagulation abnormalities. Conventional doses of glucocorticoids alone failed to improve coagulation abnormalities and the child developed large cutaneous petechiae and scalp hematomas. DIAGNOSIS: Kaposiform hemangioendothelioma combined with Kasabach-Merritt phenomenon. INTERVENTIONS: The patient received prednisolone 2.0 mg/kg*d for 4 days. Blood products were transfused to ensure vital signs and to complete the pathologic biopsy. Sirolimus combined with prednisolone was given after clarifying the diagnosis of Kaposiform hemangioendothelioma. OUTCOMES: The tumor basically disappeared on examination and the ultrasound showed a subcutaneous hyperechoic mass with normal blood flow. LESSONS: Sirolimus combined with glucocorticoids is effective in controlling Kasabach-Merritt phenomenon and pathologic biopsy is important for definitive diagnosis.


Assuntos
Transtornos da Coagulação Sanguínea , Hemangioendotelioma , Síndrome de Kasabach-Merritt , Sarcoma de Kaposi , Humanos , Recém-Nascido , Transtornos da Coagulação Sanguínea/complicações , Glucocorticoides/uso terapêutico , Hemangioendotelioma/complicações , Hemangioendotelioma/tratamento farmacológico , Hemangioendotelioma/diagnóstico , Síndrome de Kasabach-Merritt/tratamento farmacológico , Prednisolona/uso terapêutico , Sarcoma de Kaposi/patologia , Sirolimo/uso terapêutico
9.
Arch Virol ; 169(5): 98, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619650

RESUMO

Kaposi's sarcoma-associated herpesvirus (KSHV) causes Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. The tegument is a structure that is unique to herpesviruses that includes host and viral proteins, including the viral ORF42 and ORF55 proteins. Alphaherpesvirus tegument proteins have been well studied, but much is unknown regarding KSHV. Here, we report an interaction between the ORF42 and ORF55 proteins. ORF55 interacted with and recruited ORF42 from the nucleus to the cytoplasm. When ORF42 and ORF55 were expressed simultaneously in cultured cells, the expression level of these two viral proteins was higher than when either was expressed independently. ORF55, but not ORF42, was polyubiquitinated, suggesting that an unidentified regulatory mechanism may be present. A recombinant virus with an ectopic stop codon in ORF42 exhibited normal replication of genomic DNA, but fewer virus particles were released with the recombinant than with the wild-type virus. A unique R136Q mutation in ORF42, which is found in a KSHV strain that is prevalent on Miyako Island, Okinawa Prefecture, Japan, further increased the expression of ORF42 and ORF55 when these proteins were expressed simultaneously. However, the ORF42 R136Q mutation did not affect the localization pattern of ORF42 itself or of ORF55. In addition, experiments with a recombinant virus possessing the ORF42 R136Q mutation showed lower levels of production of the mutant virus than of the wild-type virus, despite similar levels of genome replication. We suggest that the R136Q mutation in ORF42 plays an important role in ORF55 protein expression and virus production.


Assuntos
Herpesvirus Humano 8 , Sarcoma de Kaposi , Humanos , Herpesvirus Humano 8/genética , Citoplasma , Japão , Proteínas Virais/genética
10.
BMC Infect Dis ; 24(1): 454, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684967

RESUMO

BACKGROUND: Clinically, most patients with Kaposi's sarcoma (KS) are male, and several direct and indirect mechanisms may underlie this increased susceptibility in men, Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is considered to be the primary etiological agent responsible for KS. Thus, we propose the hypothesis that men are more susceptible to HHV-8 infection, leading to a higher incidence of Kaposi's sarcoma among males. A meta-analysis was conducted to evaluate the association between gender and HHV-8 seropositivity in the general population. METHODS: A comprehensive literature search was performed using 6 online databases: PubMed, EMBASE, Cochrane library, Web of Science, CNKI, and Wanfang. Studies published before March 15, 2023, were included. RESULTS: In all, 33 articles including 41 studies were included in the meta-analysis. In the included adult population. men had a higher risk of HHV-8 infection than did women in adult populations from all over the world (odds ratio [OR]: 1.08, 95% confidence interval [CI]: 1.01-1.15), but no differences were found in child population from all over the world (OR: 0.90, 95% CI: 0.79-1.01). There was a significant difference in HHV-8 seroprevalence between men and women in sub-Saharan Africa (SSA) adult population (OR: 1.15, 95% CI: 1.05-1.26). However, no significant differences were observed in sub-Saharan Africa (SSA) child population (OR: 0.90, 95%CI 0.78-1.03). As for other continents, the results showed no significant difference, such as the Asian population (OR: 1.03, 95%CI: 0.92-1.16). or the European and American populations (OR 1.01, 95%CI 0.87-1.17). CONCLUSION: There was a slight gender disparity for HHV-8 infection in the adult population. Among the adult populations from SSA and globally, men were more likely to be infected with HHV-8 than were women. However, no statistical significance was observed in the child populations from SSA and globally. In the future, the inclusion of more standardized studies may strengthen the results of this study.


Assuntos
Infecções por Herpesviridae , Herpesvirus Humano 8 , Sarcoma de Kaposi , Humanos , Masculino , Feminino , Infecções por Herpesviridae/epidemiologia , Infecções por Herpesviridae/virologia , Sarcoma de Kaposi/epidemiologia , Sarcoma de Kaposi/virologia , Fatores Sexuais , Adulto , Incidência , Fatores de Risco , Criança
12.
Viruses ; 16(3)2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38543814

RESUMO

Seasonal coronaviruses (HCoVs) are known to contribute to cross-reactive antibody (Ab) responses against SARS-CoV-2. While these responses are predictable due to the high homology between SARS-CoV-2 and other CoVs, the impact of these responses on susceptibility to SARS-CoV-2 infection in cancer patients is unclear. To investigate the influence of prior HCoV infection on anti-SARS-CoV-2 Ab responses among COVID-19 asymptomatic individuals with cancer and controls without cancers, we utilized the VirScan technology in which phage immunoprecipitation and sequencing (PhIP-seq) of longitudinal plasma samples was performed to investigate high-resolution (i.e., epitope level) humoral CoV responses. Despite testing positive for anti-SARS-CoV-2 Ab in the plasma, a majority of the participants were asymptomatic for COVID-19 with no prior history of COVID-19 diagnosis. Although the magnitudes of the anti-SARS-CoV-2 Ab responses were lower in individuals with Kaposi sarcoma (KS) compared to non-KS cancer individuals and those without cancer, the HCoV Ab repertoire was similar between individuals with and without cancer independent of age, sex, HIV status, and chemotherapy. The magnitudes of the anti-spike HCoV responses showed a strong positive association with those of the anti-SARS-CoV-2 spike in cancer patients, and only a weak association in non-cancer patients, suggesting that prior infection with HCoVs might play a role in limiting SARS-CoV-2 infection and COVID-19 disease severity.


Assuntos
COVID-19 , Neoplasias , Sarcoma de Kaposi , Humanos , SARS-CoV-2 , Formação de Anticorpos , Teste para COVID-19 , Estações do Ano , Anticorpos Antivirais , Epitopos , Glicoproteína da Espícula de Coronavírus
15.
PLoS Pathog ; 20(3): e1012082, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38470932

RESUMO

Ferroptosis, a defensive strategy commonly employed by the host cells to restrict pathogenic infections, has been implicated in the development and therapeutic responses of various types of cancer. However, the role of ferroptosis in oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV)-induced cancers remains elusive. While a growing number of non-histone proteins have been identified as acetylation targets, the functions of these modifications have yet to be revealed. Here, we show KSHV reprogramming of host acetylation proteomics following cellular transformation of rat primary mesenchymal precursor. Among them, SERPINE1 mRNA binding protein 1 (SERBP1) deacetylation is increased and required for KSHV-induced cellular transformation. Mechanistically, KSHV-encoded viral interleukin-6 (vIL-6) promotes SIRT3 deacetylation of SERBP1, preventing its binding to and protection of lipoyltransferase 2 (Lipt2) mRNA from mRNA degradation resulting in ferroptosis. Consequently, a SIRT3-specific inhibitor, 3-TYP, suppresses KSHV-induced cellular transformation by inducing ferroptosis. Our findings unveil novel roles of vIL-6 and SERBP1 deacetylation in regulating ferroptosis and KSHV-induced cellular transformation, and establish the vIL-6-SIRT3-SERBP1-ferroptosis pathways as a potential new therapeutic target for KSHV-associated cancers.


Assuntos
Ferroptose , Herpesvirus Humano 8 , Neoplasias , Sarcoma de Kaposi , Sirtuína 3 , Ratos , Animais , Herpesvirus Humano 8/genética , Sirtuína 3/genética , Sirtuína 3/metabolismo , Transformação Celular Neoplásica , Proteínas Virais/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
16.
Virchows Arch ; 484(3): 423-427, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38483613

RESUMO

Most tumors are caused by inherited or acquired genetic changes. However, a subset of tumors is driven by viral infection including Kaposi sarcoma, nasopharyngeal carcinoma, and others. Human papillomavirus (HPV) is an especially common cause of epithelial cancers and hyperplasias. Epidermodysplasia verruciformis (EDV) is a rare type of HPV infection with characteristic histopathologic features and a unique spectrum of HPV subtypes. We report here a distinctive form of EDV-associated eccrine neoplasia. Seven tumors from two patients were analyzed and show highly uniform features including multiple clustered clinical lesions, multifocal epidermal origin, eccrine differentiation with close association with the acrosyringium, an anastomosing growth pattern, and a bland monotonous poroid-to-basaloid cytomorphology. Clinical follow-up for one patient has been benign to date. These tumors show strong similarity to two previously reported cases, suggesting that this type of EDV-associated eccrine neoplasia may represent a rare but reproducible form of skin adnexal tumor with distinctive clinicopathologic features.


Assuntos
Epidermodisplasia Verruciforme , Infecções por Papillomavirus , Sarcoma de Kaposi , Neoplasias Cutâneas , Neoplasias das Glândulas Sudoríparas , Humanos , Epidermodisplasia Verruciforme/genética , Epidermodisplasia Verruciforme/patologia , Neoplasias Cutâneas/complicações , Papillomaviridae/genética
18.
Cesk Slov Oftalmol ; 80(2): 114-118, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38531684

RESUMO

AIM: The aim of this case report is to present the case of a patient with iatrogenic Kaposi's sarcoma afflicting several organs, ocular manifestation. CASE REPORT: In a 74-year-old kidney transplant patient receiving immunosuppressive therapy, iatrogenic Kaposi's sarcoma (KS) developed in both lower eyelids. Subsequently, KS was confirmed in the region of the left forearm, with suspicion of lesions in the lungs. The ocular tumor was surgically removed with negative margins, requiring no further therapy. The lesion on the left forearm was completely excised. The patient underwent radiotherapy for the lung lesions, and immunosuppressive therapy was reduced. CONCLUSION: The case highlights the importance of early identification of KS, its histological verification, radical resection, and multidisciplinary collaboration. Knowledge of the epidemiology of this condition is a key factor in determining the correct diagnosis.


Assuntos
Sarcoma de Kaposi , Humanos , Idoso , Sarcoma de Kaposi/diagnóstico , Sarcoma de Kaposi/etiologia , Sarcoma de Kaposi/patologia , Terapia de Imunossupressão/efeitos adversos , Doença Iatrogênica
19.
J Cancer Res Ther ; 20(1): 469-471, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38554367

RESUMO

Kaposi's sarcoma (KS) is an angiogenic tumor. KS lesions frequently develop in the skin and oral cavity mucosa in the head and neck regions, and pure laryngeal localization is extremely rare. We reported a 64-year-old male patient without HIV, HBV, and HCV positivity presented with a hemangiomatous lesion detected incidentally in the right vocal cord. Biopsy was taken for histopathological and immunohistochemical evaluation. Examination revealed that spindle cells were of vascular origin and expressed HHV-8, a specific marker associated with Kaposi's sarcoma-associated herpesvirus. Positron emission tomography-computed tomography (PET/CT) demonstrated an increased fluorodeoxyglucose (FDG) uptake in the vocal cord. The patient was treated with a 30 Gy volumetric arc plan. Disease-free follow-up continues in the first year after low-dose definitive RT. This is the first case report of KS in the vocal cord in which the most detailed data about RT were shared.


Assuntos
Herpesvirus Humano 8 , Sarcoma de Kaposi , Masculino , Humanos , Pessoa de Meia-Idade , Sarcoma de Kaposi/diagnóstico , Sarcoma de Kaposi/radioterapia , Prega Vocal , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Pele/patologia
20.
Rinsho Ketsueki ; 65(2): 74-77, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38448001

RESUMO

An 80-year-old Japanese man presented with systemic lymphadenopathy, including the para-aortic area and left inguinal nodes, which was diagnosed as diffuse large B-cell lymphoma (DLBCL) and human herpesvirus (HHV) 8-positive/HIV-negative Kaposi's sarcoma (KS). Immunohistochemical examination revealed that the lymphoma cells were negative for HHV-8. The patient received combined chemotherapy with rituximab, pirarubicin, cyclophosphamide, vincristine, and prednisolone for six cycles and achieved complete remission. In the literature, five cases of simultaneous appearance of malignant lymphoma and KS in the same lymph node have been reported, but DLBCL as a histological subtype has not yet been reported.


Assuntos
Herpesvirus Humano 8 , Linfoma Difuso de Grandes Células B , Sarcoma de Kaposi , Masculino , Humanos , Idoso de 80 Anos ou mais , Sarcoma de Kaposi/complicações , Sarcoma de Kaposi/tratamento farmacológico , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfonodos , HIV
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