Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma

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.

Download Full-text

Differential Expression of Viral Bcl-2 Encoded by Kaposi's Sarcoma-Associated Herpesvirus and Human Bcl-2 in Primary Effusion Lymphoma Cells and Kaposi's Sarcoma Lesions

Journal of Virology ◽

10.1128/jvi.76.5.2551-2556.2002 ◽

2002 ◽

Vol 76 (5) ◽

pp. 2551-2556 ◽

Cited By ~ 23

Author(s):

Isabelle Widmer ◽

Marion Wernli ◽

Felix Bachmann ◽

Fred Gudat ◽

Gieri Cathomas ◽

...

Keyword(s):

Kaposi's Sarcoma ◽

Mononuclear Cells ◽

Primary Effusion Lymphoma ◽

Human Herpesvirus ◽

Kaposi’S Sarcoma ◽

Human Herpesvirus 8 ◽

Lymphoma Cells ◽

Herpesvirus 8 ◽

Primary Effusion Lymphoma Cell ◽

Spindle Cells

ABSTRACT Expression of human herpesvirus 8 viral Bcl-2 protein was demonstrated in spindle cells of late-stage Kaposi's sarcoma lesions but not in primary effusion lymphoma cell lines. In contrast, strong expression of human Bcl-2 was found in stimulated primary effusion lymphoma cells, whereas in Kaposi's sarcoma lesions preferential mononuclear cells, and to a lesser extent spindle cells, stained positive.

Download Full-text

The size and conformation of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) DNA in infected cells and virions.

Journal of Virology ◽

10.1128/jvi.70.11.8151-8154.1996 ◽

1996 ◽

Vol 70 (11) ◽

pp. 8151-8154 ◽

Cited By ~ 159

Author(s):

R Renne ◽

M Lagunoff ◽

W Zhong ◽

D Ganem

Keyword(s):

Kaposi's Sarcoma ◽

Human Herpesvirus ◽

Kaposi’S Sarcoma ◽

Human Herpesvirus 8 ◽

Herpesvirus 8 ◽

Infected Cells ◽

Kaposi's Sarcoma Associated Herpesvirus ◽

Kaposi’S Sarcoma Associated Herpesvirus

Download Full-text

Transcription Program of Human Herpesvirus 8 (Kaposi's Sarcoma-Associated Herpesvirus)

Journal of Virology ◽

10.1128/jvi.75.10.4843-4853.2001 ◽

2001 ◽

Vol 75 (10) ◽

pp. 4843-4853 ◽

Cited By ~ 168

Author(s):

Mini Paulose-Murphy ◽

Nguyen-Khoi Ha ◽

Chunsheng Xiang ◽

Yidong Chen ◽

Laura Gillim ◽

...

Keyword(s):

Kaposi's Sarcoma ◽

Primary Effusion Lymphoma ◽

Human Herpesvirus ◽

Viral Gene Expression ◽

Kaposi’S Sarcoma ◽

Lytic Replication ◽

Human Herpesvirus 8 ◽

Viral Gene ◽

Herpesvirus 8 ◽

Transcription Program

ABSTRACT Human herpesvirus 8 (HHV-8), a gammaherpesvirus implicated in Kaposi's sarcoma, primary effusion lymphoma, and Castleman's disease, encodes several pathogenically important cellular homologs. To define the HHV-8 transcription program, RNA obtained from latently infected body cavity-based lymphoma 1 cells induced to undergo lytic replication was used to query a custom HHV-8 DNA microarray containing nearly every known viral open reading frame. The patterns of viral gene expression offer insights into the replication and pathogenic strategies of HHV-8.

Download Full-text

Spectrum of Kaposi's Sarcoma-Associated Herpesvirus, or Human Herpesvirus 8, Diseases

Clinical Microbiology Reviews ◽

10.1128/cmr.15.3.439-464.2002 ◽

2002 ◽

Vol 15 (3) ◽

pp. 439-464 ◽

Cited By ~ 197

Author(s):

Dharam V. Ablashi ◽

Louise G. Chatlynne ◽

James E. Whitman, ◽

Ethel Cesarman

Keyword(s):

Dna Sequences ◽

Kaposi's Sarcoma ◽

Primary Effusion Lymphoma ◽

Human Herpesvirus ◽

Kaposi’S Sarcoma ◽

B Cell Lymphoma ◽

Human Herpesvirus 8 ◽

Herpesvirus 8 ◽

Kaposi's Sarcoma Associated Herpesvirus ◽

Kaposi’S Sarcoma Associated Herpesvirus

SUMMARY Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), discovered in 1994, is a human rhadinovirus (gamma-2 herpesvirus). Unlike other human herpesviruses (herpes simplex virus, Epstein-Barr virus, varicella-zoster virus, cytomegalovirus, HHV-6, and HHV-7), it is not widespread in the general population and has many unique proteins. HHV-8 is strongly associated with all subtypes of Kaposi's sarcoma (KS), multicentric Castleman's disease, and a rare form of B-cell lymphoma, primary effusion lymphoma. In addition, HHV-8 DNA sequences have been found in association with other diseases, but the role of the virus in these diseases is largely unconfirmed and remains controversial. The seroprevalence of HHV-8, based on detection of latent and lytic proteins, is 2 to 5% in healthy donors except in certain geographic areas where the virus is endemic, 80 to 95% in classic KS patients, and 40 to 50% in HIV-1 patients without KS. This virus can be transmitted both sexually and through body fluids (e.g., saliva and blood). HHV-8 is a transforming virus, as evidenced by its presence in human malignancies, by the in vitro transforming properties of several of its viral genes, and by its ability to transform some primary cells in culture. It is not, however, sufficient for transformation, and other cofactors such as immunosuppressive cytokines are involved in the development of HHV-8-associated malignancies. In this article, we review the biology, molecular virology, epidemiology, transmission, detection methods, pathogenesis, and antiviral therapy of this newly discovered human herpesvirus.

Download Full-text