Diversity of human herpesvirus 8 genotypes in patients with AIDS and non-AIDS associated Kaposi's sarcoma, Castleman's disease and primary effusion lymphoma in Argentina

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.

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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.

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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.

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Transcription Pattern of Human Herpesvirus 8 Open Reading Frame K3 in Primary Effusion Lymphoma and Kaposi's Sarcoma

Journal of Virology ◽

10.1128/jvi.75.22.11261a-11261a.2001 ◽

2001 ◽

Vol 75 (22) ◽

pp. 11261-11261

Author(s):

Paola Rimessi ◽

Angela Bonaccorsi ◽

Michael Stürzl ◽

Marina Fabris ◽

Egidio Brocca-Cofano ◽

...

Keyword(s):

Kaposi's Sarcoma ◽

Primary Effusion Lymphoma ◽

Human Herpesvirus ◽

Kaposi’S Sarcoma ◽

Open Reading Frame ◽

Human Herpesvirus 8 ◽

Reading Frame ◽

Herpesvirus 8 ◽

Transcription Pattern

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Human Herpesvirus 8 K1 Blocks Fas in Cells and Mice by Binding and Blocking Fas.

Blood ◽

10.1182/blood.v110.11.515.515 ◽

2007 ◽

Vol 110 (11) ◽

pp. 515-515

Author(s):

Hoyoung Maeng ◽

Suizhao Wang ◽

Zuzuna Berkova ◽

Shu Wang ◽

Jaehoon Jung ◽

...

Keyword(s):

Kaposi's Sarcoma ◽

Primary Effusion Lymphoma ◽

Human Herpesvirus ◽

Kaposi’S Sarcoma ◽

Human Herpesvirus 8 ◽

Terminal Deoxynucleotidyl Transferase ◽

Dependent Manner ◽

Intact Cells ◽

Herpesvirus 8 ◽

In Cells

Abstract Background: Kaposi’s sarcoma and primary effusion lymphoma are linked to human herpesvirus 8 (HHV-8 or Kaposi’s sarcoma-associated virus) infection. Key to the pathogenesis of these cancers is the HHV-8 transmembrane oncoprotein K1. This viral protein, which immortalizes cells, produces lymphoproliferation and lymphomas through unknown mechanisms when expressed in mice. Results: We show here that K1 blocks Fas (CD95)-mediated apoptosis by binding the ectodomain of K1 to Fas in hematopoietic cancer cells (BJAB, U937 and THP-1). K1 bound to Fas in K1-transfected BJAB cells. To assess whether K1 and Fas formed complexes in cells, we chemically crosslinked proteins in transfected cells using 3,3′-dithiobissulfosuccinimidyl propionate in the presence of N-ethyl maleimide. Stabled K1-Fas complexes were present in intact cells despite blocking of free reactive cysteines. The selective ability of K1 to antagonize Fas-mediated apoptosis was strictly dependent on having its immunoreceptor tyrosine-based activation motif (ITAM). Using activating anti-Fas (CH-11) and nonactivating anti-Fas (B10) antibodies in a serial manner, we showed that K1 associated with Fas that was not activated, strongly suggesting that K1 prevents Fas from being activated. Mice transfected with K1 were protected from the apoptosis inducing effects of agonistic Jo2 anti-Fas antibody and tissues from these mice contained K1-Fas complexes. K1-transfected compared to vector-transfected mice had fewer terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling positive cells (13 ± 3% vs. 60 ± 7%, P=0.008), fewer activated caspase 3 positive cells (24 ± 5% vs. 88 ± 6%, P=0.006). Tissues had less hemorrhaging, and necrosis. Conclusion: These data support a mechanism of K1 direct binding to and blockage by K1 to Fas in suppression of apoptosis in an ITAM-dependent manner, which may be a key step in lymphoma development.

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Transcription Pattern of Human Herpesvirus 8 Open Reading Frame K3 in Primary Effusion Lymphoma and Kaposi's Sarcoma

Journal of Virology ◽

10.1128/jvi.75.15.7161-7174.2001 ◽

2001 ◽

Vol 75 (15) ◽

pp. 7161-7174 ◽

Cited By ~ 24

Author(s):

Paola Rimessi ◽

Angela Bonaccorsi ◽

Michael Stürzl ◽

Marina Fabris ◽

Egidio Brocca-Cofano ◽

...

Keyword(s):

Kaposi's Sarcoma ◽

Primary Effusion Lymphoma ◽

Human Herpesvirus ◽

Kaposi’S Sarcoma ◽

Open Reading Frame ◽

Human Herpesvirus 8 ◽

Reading Frame ◽

Herpesvirus 8 ◽

Rna Molecules ◽

Spindle Cells

ABSTRACT Human herpesvirus 8 (HHV-8) is found in immunoblastic B cells of patients with multicentric Castleman's disease (MCD) and, predominantly in a latent form, in primary effusion lymphoma (PEL) cells and Kaposi's sarcoma (KS) spindle cells. Recent studies have shown that upon reactivation, HHV-8 expresses factors that downregulate major histocompatibility class I proteins and coactivation molecules and that may enable productively infected cells to escape cytotoxic T lymphocytes and natural killer cell responses. One of these viral factors is encoded by open reading frame (ORF) K3. Here we show that in PEL cells, ORF K3 is expressed through viral transcripts that are induced very early upon virus reactivation, including bicistronic RNA molecules containing coding sequences from viral ORFs K3 and 70. Specifically, we found that a bicistronic transcript was expressed in the absence of de novo protein synthesis, thereby identifying a novel HHV-8 immediate-early gene product. Several features of the RNA molecules encoding the K3 product, including multiple transcriptional start sites, multiple donor splicing sites, and potential alternative ATG usage, suggest that there exists a finely tuned modulation of ORF K3 expression. By contrast, ORF K3 transcripts are not detected in the majority of cells present in KS lesions that are latently infected by the virus, suggesting that there are other, as-yet-unknown mechanisms of immune evasion for infected KS spindle cells. Nevertheless, because HHV-8 viremia precedes the development of KS lesions and is associated with the recrudescence of MCD symptoms, the prompt expression of ORF K3 in productively infected circulating cells may be important for virus pathogenesis. Thus, molecules targeting host or viral factors that activate ORF K3 expression or inactivate the biological functions of the K3 product should be exploited for the prevention or treatment of HHV-8-associated diseases in at-risk individuals.

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