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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Kaposi's sarcoma is the most common neoplasm among human immunodeficiency virus-positive individuals. Like other herpesviruses, KSHV is able to establish a predominantly latent, life-long infection in its host. The KSHV lytic cycle can be triggered by a number of stimuli that induce the expression of the key lytic switch protein, the replication and transcription activator (RTA) encoded by Orf50. The expression of Rta is necessary and sufficient to trigger the full lytic program resulting in the ordered expression of viral proteins, release of viral progeny, and host cell death. We have characterized an unknown open reading frame, Orf49, which lies adjacent and in the opposite orientation to Orf50. Orf49 is expressed during the KSHV lytic cycle and shows early transcription kinetics. We have mapped the 5' and 3' ends of the unspliced Orf49 transcript, which encodes a 30-kDa protein that is localized to both the nucleus and the cytoplasm. Interestingly, we found that Orf49 was able to cooperate with Rta to activate several KSHV lytic promoters containing AP-1 sites. The Orf49-encoded protein was also able to induce transcriptional activation through c-Jun but not the ATF1, ATF2, or CREB transcription factor. We found that Orf49 could induce phosphorylation and activation of the transcription factor c-Jun, the Jun N-terminal kinase (JNK), and p38. Our data suggest that Orf49 functions to activate the JNK and p38 pathways during the KSHV lytic cycle.
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PMID:Identification and characterization of the Orf49 protein of Kaposi's sarcoma-associated herpesvirus. 1650 Nov 15

Rhesus rhadinovirus (RRV) is closely related to Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) and causes KSHV-like diseases in immunocompromised rhesus macaques (RM) that resemble KSHV-associated diseases including multicentric Castleman's disease and non-Hodgkin's lymphoma. RRV retains a majority of open reading frames (ORFs) postulated to be involved in the pathogenesis of KSHV and is the closest available animal model to KSHV infection in humans. Here we describe the generation of a recombinant clone of RRV strain 17577 (RRV(17577)) utilizing bacterial artificial chromosome (BAC) technology. Characterization of the RRV BAC demonstrated that it is a pathogenic molecular clone of RRV(17577), producing virus that behaves like wild-type RRV both in vitro and in vivo. Specifically, BAC-derived RRV displays wild-type growth properties in vitro and readily infects simian immunodeficiency virus-infected RM, inducing B cell hyperplasia, persistent lymphadenopathy, and persistent infection in these animals. This RRV BAC will allow for rapid genetic manipulation of the RRV genome, facilitating the creation of recombinant versions of RRV that harbor specific alterations and/or deletions of viral ORFs. This system will provide insights into the roles of specific RRV genes in various aspects of the viral life cycle and the RRV-associated pathogenesis in vivo in an RM model of infection. Furthermore, the generation of chimeric versions of RRV containing KSHV genes will allow analysis of the function and contributions of KSHV genes to viral pathogenesis by using a relevant primate model system.
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PMID:Construction of an infectious rhesus rhadinovirus bacterial artificial chromosome for the analysis of Kaposi's sarcoma-associated herpesvirus-related disease development. 1721 83

Plasmablastic microlymphoma (PML) is defined as the accumulation of monotypic but polyclonal plasmablasts in lymphoid tissues involved in human herpes virus 8 (HHV-8)-positive multicentric Castleman's disease (MCD). So far, the nature of this very rare condition remains poorly determined. In this study, we describe a human immunodeficiency virus (HIV)-seropositive patient who developed a PML in the setting of HHV-8-positive MCD. In contrast to the cases previously reported, most of the plasmablasts in our patient were localized within the germinal center (GC) of lymphoid follicles. These plasmablasts expressed the multiple myeloma-1/interferon regulatory factor-4 (MUM1/IRF4) protein as well as IgMlambda in a monotypic fashion. They did not show any immunoreactivity with antibodies directed against Pax-5, CD20, CD79a, CD10, CD30, CD23, CD138, epithelial membrane antigen (EMA) or BCL-6. These cells exhibited a high proliferation rate, expressed the HHV-8 latent nuclear antigen-1, and secreted the HHV-8 viral homologue of human interleukin-6. Polymerase chain reaction analysis did not demonstrate any clonal rearrangement of the genes coding for the heavy chain of the immunoglobulin. Moreover, no Epstein-Barr virus (EBV) RNA transcript could be found, using in situ hybridization. The present case illustrates that PML may arise within the GC of lymphoid follicles in the absence of EBV coinfection. In our opinion, PML occurring in MCD likely represents a variant of HHV-8-positive MCD in which lytic HHV-8 replication is particularly prominent, due to a local or systemic immune imbalance.
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PMID:Plasmablastic microlymphoma occurring in human herpesvirus 8 (HHV-8)-positive multicentric Castleman's disease and featuring a follicular growth pattern. 1761 57

The escalating pandemic of the acquired immunodeficiency disease in sub-Saharan Africa is associated with an increasing incidence of the lymphoproliferative disorders where evidence shows that highly active retroviral therapy can reconstitute immunologic competence and, at least in some groups exemplified by Kaposi's sarcoma, result in an outcome comparable to uninfected controls. Paradoxically other subtypes are less responsive exemplified by Burkitt lymphoma and multicentric Castleman's disease, where they are localised and may present after starting treatment. This association provides a model to test the concept that pathogenesis may reflect an aberrant response to antigens including human herpesvirus-8 thereby renewing focus on proactive inclusion of anti-herpes drugs with conventional treatment for retrovirus particularly prior to initiating chemotherapy.
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PMID:Castleman's disease and retroviral therapy. 1793 77

Kaposi sarcoma (KS), multicentric Castleman's disease (MCD), and plasmablastic microlymphoma, are all linked to human herpesvirus-8 (HHV-8) infection and HIV-induced immunodeficiency. Herein, we describe the case of a Kenyan man diagnosed with HIV in 2000. He deferred highly active antiretroviral therapy (HAART) and remained in good health until his CD4+ count declined in 2006. He was hospitalized with bacterial pneumonia in 2008, after which he agreed to take HAART but did so sporadically. In 2010, he was hospitalized with fever, lymphadenopathy, pancytopenia, and an elevated HHV-8 viral load. A lymph node biopsy showed findings consistent with KS, MCD, and plasmablastic microlymphoma. Eight months after starting liposomal doxorubicin, Rituximab, and a new HAART regimen, he has improved clinically, and his HIV and HHV-8 viral loads are suppressed. These three conditions, found in the same lymph node, underscore the inflammatory and malignant potential of HHV-8, particularly in the milieu of HIV-induced immunodeficiency.
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PMID:Human Herpesvirus-8 Infection Associated with Kaposi Sarcoma, Multicentric Castleman's Disease, and Plasmablastic Microlymphoma in a Man with AIDS: A Case Report with Review of Pathophysiologic Processes. 2125 46

Viral interleukin-6 (vIL-6) is a product of Kaposi's sarcoma-associated herpesvirus (KSHV) expressed in latently infected cells and to a higher degree during viral replication. A distinctive feature of vIL-6 is the ability to directly bind and activate gp130 signaling in the absence of other receptor subunits. Secretion of vIL-6 is generally poor, but vIL-6 can activate gp130 from inside the cell. Due to the wide cell distribution of gp130, vIL-6 has the potential to induce a wide range of biological effects. Expression of vIL-6 is variable in KSHV-associated Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), multicentric Castleman's disease (MCD), and in a newly described MCD-like systemic inflammatory syndrome observed in human immunodeficiency virus-positive patients. PEL effusions usually contain vIL-6 at high concentrations; since vIL-6 induces vascular endothelial growth factor, vIL-6 likely contributes to vascular permeability and formation of PEL effusions. Lymph nodes affected with MCD contain vIL-6-positive cells, and vIL-6 levels rise in conjunction with flares of the disease and likely contribute to symptoms of inflammation. The development of vIL-6 inhibitors is a potentially important advance in the treatment of KSHV-associated malignancies where vIL-6 is expressed.
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PMID:Viral interleukin-6: role in Kaposi's sarcoma-associated herpesvirus: associated malignancies. 2176 54

Our case illustrates the difficulties involved in diagnosing multicentric Castleman's disease (MCD) in a human immunodeficiency virus-infected man with febrile episodes and malaise. In the absence of well-established treatment protocols, we have chosen a new treatment algorithm with rituximab, etoposide, and valganciclovir, which led to the remission of clinical symptoms. Yet, we advocate focused exploration for MCD in immunosuppressed patients with unclear febrile episodes, as recent advances in treatment are promising.
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PMID:Multicentric Castleman's disease as a cause for unclear febrile episodes in a 55-year-old HIV-infected man. 2183 51

We report a case of successive bilateral retinal vein occlusion in a human immunodeficiency virus (HIV)-positive male with multicentric Castleman's disease treated successfully with a single injection of intravitreal bevacizumab. Castleman's disease should be a differential diagnosis of occlusive retinovascular disease and, occasionally, ocular manifestation can lead to systemic diagnosis.
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PMID:Retinal vein occlusion during flare of multicentric Castleman's disease. 2398 53

Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV), formally designated human herpesvirus 4 (HHV-4) and 8 (HHV-8), respectively, are viruses that can cause a variety of cancers in humans. EBV is found in non-Hodgkin and Hodgkin lymphomas, as well as in lymphoproliferative disorders, which occur more commonly but not exclusively in individuals with immunodeficiency. EBV also causes nonlymphoid malignancies such as nasopharyngeal carcinoma. KSHV causes primary effusion lymphomas, multicentric Castleman's disease, and Kaposi's sarcoma. The frequency of lymphoid malignancies related to infection by one of these two herpesviruses is greatly increased in individuals with immunodeficiency, whether primary or acquired, for example, as a consequence of HIV infection and AIDS or in the case of therapeutic immunosuppression for organ transplantation. Our current understanding indicates that EBV and KSHV contribute to lymphomagenesis by affecting genomic stability and by subverting the cellular molecular signaling machinery and metabolism to avoid immune surveillance and enhance tumor cell growth and survival. Understanding the viral associations in specific lymphoproliferative disorders and the molecular mechanisms of viral oncogenesis will lead to better prevention, diagnosis, and treatment strategies for these diseases.
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PMID:Gammaherpesviruses and lymphoproliferative disorders. 2411 11

A 46-year-old man presented with a high-grade fever, multiple lymphadenopathies, hepatosplenomegaly and human immunodeficiency virus (HIV) seropositivity, without severe immunosuppression. We suspected human herpesvirus-8 (HHV-8)-associated multicentric Castleman's disease (MCD) based on the results of a physical examination and laboratory investigations, including bone marrow aspiration. However, the patient died eight days after admission due to multiorgan failure. An autopsy revealed MCD and lymphoma cell infiltration in multiple organs. The final diagnosis was large B-cell lymphoma (LBCL) arising in HHV-8-associated MCD. This case illustrates the potential for LBCL in HHV-8 MCD in HIV-infected patients with hepatosplenomegaly and lymphadenopathy without severe immunosuppression and highlights the clinical significance of bone marrow aspiration.
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PMID:Rapid multiorgan failure due to large B-cell lymphoma arising in human herpesvirus-8-associated multicentric Castleman's disease in a patient with human immunodeficiency virus infection. 2550 Apr 43


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