Human Herpesvirus-8–Positive Microvenular Hemangioma in POEMS Syndrome

2003 ◽  
Vol 127 (8) ◽  
pp. 1034-1036 ◽  
Author(s):  
S. David Hudnall ◽  
Tiansheng Chen ◽  
Kelty Brown ◽  
Tiffany Angel ◽  
Mary R. Schwartz ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
African American Woman ◽  
American Woman ◽  
Human Herpesvirus ◽  
Castleman Disease ◽  
Human Herpesvirus 8 ◽  
Herpesvirus 8 ◽  
First Case ◽  
Initial Symptoms ◽  
Night Sweats

Abstract We report a case of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome in a 55-year-old African American woman in which human herpesvirus-8 (HHV-8) was demonstrated within rare lymphocytes in a Castleman disease lymph node biopsy and numerous endothelial cells and lymphocytes in a microvenular hemangioma skin biopsy. Initial symptoms and findings of night sweats, weight loss, anorexia, generalized lymphadenopathy, and hemangiomas improved after chemotherapy with cyclophosphamide and prednisone. However, in the year following the initial diagnosis, the patient suffered from recurrent bouts of night sweats, gastroparesis, and lymphadenopathy, which required further treatment with plasmapheresis, cyclophosphamide, prednisone, and rituximab. One year later, the patient is asymptomatic but has persistent gammopathy. Although HHV-8 has previously been detected in POEMS-associated Castleman disease tissue, to our knowledge, this is the first case report in which HHV-8 has been directly demonstrated within the endothelial cells of a POEMS-associated hemangioma.

scholarly journals Activation of NF-κB by the Human Herpesvirus 8 Chemokine Receptor ORF74: Evidence for a Paracrine Model of Kaposi's Sarcoma Pathogenesis

2001 ◽  
Vol 75 (18) ◽  
pp. 8660-8673 ◽  
Author(s):  
Shibani Pati ◽  
Marielle Cavrois ◽  
Hong-Guang Guo ◽  
James S. Foulke ◽  
Jynho Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Kaposi's Sarcoma ◽  
Vascular Endothelial Cells ◽  
Inositol Phosphate ◽  
Human Herpesvirus ◽  
Kaposi’S Sarcoma ◽  
Lymphoid Cells ◽  
Human Herpesvirus 8 ◽  
Herpesvirus 8 ◽  
Latently Infected

ABSTRACT Infection with human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma (KS)-associated herpesvirus, is necessary for the development of KS. The HHV-8 lytic-phase gene ORF74 is related to G protein-coupled receptors, particularly interleukin-8 (IL-8) receptors. ORF74 activates the inositol phosphate/phospholipase C pathway and the downstream mitogen-activated protein kinases, JNK/SAPK and p38. We show here that ORF74 also activates NF-κB independent of ligand when expressed in KS-derived HHV-8-negative endothelial cells or primary vascular endothelial cells. NF-κB activation was enhanced by the chemokine GROα, but not by IL-8. Mutation of Val to Asp in the ORF74 second cytoplasmic loop did not affect ligand-independent signaling activity, but it greatly increased the response to GROα. ORF74 upregulated the expression of NF-κB-dependent inflammatory cytokines (RANTES, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor) and adhesion molecules (VCAM-1, ICAM-1, and E-selectin). Supernatants from transfected KS cells activated NF-κB signaling in untransfected cells and elicited the chemotaxis of monocytoid and T-lymphoid cells. Expression of ORF74 conferred on primary endothelial cells a morphology that was strikingly similar to that of spindle cells present in KS lesions. Taken together, these data, demonstrating that ORF74 activates NF-κB and induces the expression of proangiogenic and proinflammatory factors, suggest that expression of ORF74 in a minority of cells in KS lesions could influence uninfected cells or latently infected cells via autocrine and paracrine mechanisms, thereby contributing to KS pathogenesis.

scholarly journals Inhibition of Infection and Replication of Human Herpesvirus 8 in Microvascular Endothelial Cells by Alpha Interferon and Phosphonoformic Acid

2004 ◽  
Vol 78 (15) ◽  
pp. 8359-8371 ◽  
Author(s):  
Laurie T. Krug ◽  
Veronika P. Pozharskaya ◽  
Yimin Yu ◽  
Naoki Inoue ◽  
Margaret K. Offermann
Keyword(s):  
Endothelial Cells ◽  
Infectious Virus ◽  
Human Herpesvirus ◽  
Lytic Replication ◽  
Alpha Interferon ◽  
Human Herpesvirus 8 ◽  
Microvascular Endothelial Cells ◽  
Herpesvirus 8 ◽  
Phosphonoformic Acid ◽  
Infected Cells

ABSTRACT Infection of endothelial cells with human herpesvirus 8 (HHV-8) is an essential event in the development of Kaposi's sarcoma. When primary microvascular endothelial cells (MECs) were infected with HHV-8 at a low multiplicity of infection, considerable latent replication of HHV-8 occurred, leading to a time-dependent increase in the percentage of virus-infected cells that was accompanied by cellular spindling and growth to a high density with loss of contact inhibition. Only a low percentage of MECs supported lytic replication of HHV-8 and produced infectious virus. Phosphonoformic acid blocked production of infectious virus but did not inhibit the rapid expansion of latently infected MECs. Pretreatment of MECs with alpha interferon (IFN-α) prior to infection effectively reduced HHV-8 viral gene expression, latent replication, and production of infectious virus. High levels of the double-stranded RNA activated protein kinase (PKR) were expressed in HHV-8-infected cells, and incubation with IFN-α increased PKR expression more in virus-infected cells than in uninfected cells. MECs that were immortalized with simian virus 40 large-T antigen differed from nonimmortalized MECs in their response to infection with HHV-8 and demonstrated that cells with elevated levels of expression of antiviral transcripts expressed viral transcripts at reduced levels. These studies demonstrate that MECs respond to HHV-8 with enhanced expression of cellular antiviral genes and that augmentation of innate antiviral defenses with IFN-α is a more effective strategy than inhibition of viral lytic replication to protect MECs from infection with HHV-8 and to restrict proliferation of virus-infected MECs.

Human herpesvirus 8 enhances human immunodeficiency virus replication in acutely infected cells and induces reactivation in latently infected cells

Blood ◽  
2005 ◽  
Vol 106 (8) ◽  
pp. 2790-2797 ◽  
Author(s):  
Elisabetta Caselli ◽  
Monica Galvan ◽  
Enzo Cassai ◽  
Arnaldo Caruso ◽  
Laura Sighinolfi ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Endothelial Cells ◽  
Mononuclear Cells ◽  
Human Herpesvirus ◽  
Human Herpesvirus 8 ◽  
Human Immunodeficiency Virus Replication ◽  
Hiv Replication ◽  
Herpesvirus 8 ◽  
Immunodeficiency Virus ◽  
Infected Cells

AbstractHuman herpesvirus 8 (HHV-8) is etiologically associated with Kaposi sarcoma (KS), the most common AIDS-associated malignancy. Previous results indicate that the HHV-8 viral transactivator ORF50 interacts synergistically with Tat protein in the transactivation of human immunodeficiency virus (HIV) long terminal repeat (LTR), leading to increased cell susceptibility to HIV infection. Here, we analyze the effect of HHV-8 infection on HIV replication in monocyte-macrophage and endothelial cells, as potential targets of coinfection. Primary or transformed monocytic and endothelial cells were infected with a cell-free HHV-8 inoculum and subsequently infected with lymphotropic or monocytotropic strains of HIV. The results show that HHV-8 coinfection markedly increases HIV replication in both cell types. HHV-8 infection induces also HIV reactivation in chronically infected cell lines and in peripheral blood mononuclear cells (PBMCs) from patients with asymptomatic HIV, suggesting the possibility that similar interactions might take place also in vivo. Furthermore, coinfection is not an essential condition, since contiguity of differently infected cells is sufficient for HIV reactivation. The results suggest that HHV-8 might be a cofactor for HIV progression and that HHV-8-infected endothelial cells might play a relevant role in transendothelial HIV spread. (Blood. 2005;106:2790-2797)

scholarly journals Kaposi sarcoma–associated herpesvirus/human herpesvirus 8–associated lymphoproliferative disorders

Blood ◽  
2019 ◽  
Vol 133 (11) ◽  
pp. 1186-1190 ◽  
Author(s):  
Eric Oksenhendler ◽  
David Boutboul ◽  
Lionel Galicier
Keyword(s):  
B Cells ◽  
Primary Effusion Lymphoma ◽  
Human Herpesvirus ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Lymphoproliferative Disorders ◽  
Human Herpesvirus 8 ◽  
Herpesvirus 8 ◽  
Multicentric Castleman Disease ◽  
Infected Cells

Abstract Kaposi sarcoma–associated herpesvirus/human herpesvirus 8 is associated with multicentric Castleman disease (MCD) and primary effusion lymphoma (PEL). In MCD, infected B cells, although polyclonal, express a monotypic immunoglobulin Mλ phenotype, probably through editing toward λ light chain in mature B cells. They are considered to originate from pre–germinal center (GC) naive B cells. Both viral and human interleukin-6 contribute to the plasmacytic differentiation of these cells, and viral replication can be observed in some infected cells. PEL cells are clonal B cells considered as GC/post-GC B cells. One can also hypothesize that they originate from the same infected naive B cells and that additional factors could be responsible for their peculiar phenotype.

High levels of human herpesvirus 8 viral load, human interleukin-6, interleukin-10, and C reactive protein correlate with exacerbation of multicentric Castleman disease in HIV-infected patients

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2069-2073 ◽  
Author(s):  
Eric Oksenhendler ◽  
Guislaine Carcelain ◽  
Yoshiyasu Aoki ◽  
Emmanuelle Boulanger ◽  
Anne Maillard ◽  
...  
Keyword(s):  
Viral Load ◽  
Interleukin 6 ◽  
Lymphoproliferative Disorder ◽  
Human Herpesvirus ◽  
Castleman Disease ◽  
Human Herpesvirus 8 ◽  
C Reactive Protein ◽  
Herpesvirus 8 ◽  
Multicentric Castleman Disease ◽  
Reactive Protein

Abstract Multicentric Castleman disease (MCD) is a distinct type of lymphoproliferative disorder associated with inflammatory symptoms and interleukin-6 (IL-6) dysregulation. In the context of human immunodeficiency virus (HIV) infection, MCD is associated with human herpesvirus 8 (HHV8) infection. In a prospective study of 23 HIV-infected patients with MCD, clinical symptoms of MCD were present at 45 visits, whereas patients were in chemotherapy-induced clinical remission at 50 visits. Symptoms were associated with a high level of serum C reactive protein, high HHV8 viral load in peripheral blood mononuclear cells, and high plasma human IL-6 and IL-10 levels. Strong correlations between plasma IL-6 and plasma IL-10 with the HHV8 viral load suggest that both cytokines may be involved in the pathogenesis of this virus-associated lymphoproliferative disorder.

Human Herpesvirus-8 (HHV-8/KSHV) Induces Reactive Oxygen Species in Endothelial Cells That Facilitate Virus Infection.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 605-605 ◽  
Author(s):  
Jian Feng Wang ◽  
Xuefeng Zhang ◽  
Bala Chandran ◽  
Jerome E. Groopman
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Virus Entry ◽  
Reactive Oxygen ◽  
Human Herpesvirus ◽  
Human Herpesvirus 8 ◽  
Ros Generation ◽  
Target Cells ◽  
Oxygen Species ◽  
Herpesvirus 8

Abstract Reactive oxygen species (ROS) can activate replication of certain viruses, induce the production of various inflammatory mediators and play a critical role in carcinogenesis and tumor development. Kaposi’s sarcoma (KS) is the most prevalent HIV-associated cancer and is caused by infection with human herpesvirus-8 (HHV-8/KSHV). KS tissue has been reported to possess increased levels of ROS. We studied if ROS generation is related to HHV-8 infection and its role in virus entry into endothelial cells. Incubation of dermal microvascular endothelial cells (DMECs) with highly purified HHV-8 induced rapid increases in the production of intracellular hydrogen peroxide (H2O2), one of the major forms of ROS. Intracellular H2O2 was also induced by the treatment of DMECs with the HHV-8 envelope glycoprotein B (gB). The gB protein possesses an RGD motif, binds to the integrin molecules, alpha3 and beta1, and is a major mediator of virus entry into target cells. To test if it was integrin ligation that induces the production of ROS, we treated DMECs with fibronectin or laminin, the respective natural ligands for alpha3 and beta1 integrins. We observed a similar induction of intracellular ROS in DMECs by either matrix protein. These results indicated that the HHV-8-induced production of ROS was, at least in part, mediated by stimulation of integrins through the RGD-containing viral gB protein. ROS have recently been shown to function as second messengers in cellular signaling. To assess at which steps of cell signaling ROS may be functioning, we studied the signaling cascade in DMECs activated by the HHV-8 gB protein. Previous studies have shown that HHV-8, through gB/integrin interaction, induces cytoskeletal rearrangement and activates focal adhesion kinase (FAK), Src kinase and Akt, which are critical for virus entry into the target cells. We found that the activation of FAK, c-Src or Akt by this viral protein was inhibited by pretreatment with N-acetyl-L-cysteine (NAC), a potent thiol antioxidant. These results suggested that generation of ROS was involved in HHV-8-triggered signaling. We next examined if a change in ROS production modulated HHV-8 virus entry. We used green fluorescent protein (GFP)-labeled HHV-8 at a multiplicity of infection of 5–6, and quantitated the infection by fluorescence analysis of the DMECs. Short term exposure to low concentrations of H2O2 enhanced HHV-8 infection in DMECs, while treatment with NAC significantly decreased infection. These data indicated that ROS generation participated in HHV-8-mediated signaling and entry into target cells. Our study demonstrates a novel role of ROS in virus pathogenesis and provides a framework for the development of novel antioxidant strategies in AIDS-KS treatment.

Molecular evidence of organ-related transmission of Kaposi sarcoma–associated herpesvirus or human herpesvirus-8 in transplant patients

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3279-3281
Author(s):  
Mario Luppi ◽  
Patrizia Barozzi ◽  
Gaia Santagostino ◽  
Raffaella Trovato ◽  
Thomas F. Schulz ◽  
...  
Keyword(s):  
Genetic Relatedness ◽  
Primary Effusion Lymphoma ◽  
Human Herpesvirus ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Human Herpesvirus 8 ◽  
Molecular Evidence ◽  
Herpesvirus 8 ◽  
Transplant Patients ◽  
High Level

In transplant patients, Kaposi sarcoma (KS)-associated herpesvirus or human herpesvirus-8 (HHV-8) infection is associated with the development of KS, primary effusion lymphoma and Castleman disease. Whether HHV-8 is either reactivated in the recipient or transmitted by the donor has been investigated so far only by serologic studies. Thus, we addressed the issue of HHV-8 transmission in the transplantation setting by molecular methods. We exploited the high level variability of the orf-K1 gene and the polymorphism of theorf-73 gene of the HHV-8 genome to assess the genetic relatedness of the HHV-8 strains identified in the posttransplant KS lesions that developed, simultaneously, 20 months after transplantation, in 2 recipients of twin kidneys from the same cadaver donor. The 100% identity of nucleotide sequence of the most variable viral region and the presence of the same, singleorf-73 type in both patients provides strong molecular evidence of organ-related transmission of HHV-8 in the setting of transplantation.

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