The role of Kaposi sarcoma‐associated herpesvirus in the pathogenesis of Kaposi sarcoma

Gramolelli, Silvia; Schulz, Thomas F.

doi:10.1002/path.4441

Cited by 94 publications

(84 citation statements)

References 155 publications

(205 reference statements)

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“…HHV-8 is observed in almost HIV-positive MCD, while HHV-8 is detected in less than 40% of HIV negative cases. Concomitant KS is detectable in up to 70% of patients [31] [19,34,36 ]. Lytic infection occurs in <3% KS cells and is more frequent in MCD [19,34,35] Human T-cell lymphotropic virus type-1 (HTLV-1)…”

Section: Human Herpes Virus-8 (Hhv-8)/kaposi's Sarcoma Herpes Virus (mentioning

confidence: 99%

Immunodeficiency-associated viral oncogenesis

Pierangeli

Antonelli

Gentile

2015

Clinical Microbiology and Infection

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Several viruses with different replication mechanisms contribute to oncogenesis by both direct and indirect mechanisms in immunosuppressed subjects after solid organ transplantation, after allogeneic stem cell transplantation, or with human immunodeficiency virus (HIV) infection. Epstein-Barr virus (EBV), human papillomavirus (HPV), Kaposi sarcoma herpesvirus (KSHV), human T-cell lymphotropic virus type 1 (HTLV-1) and Merkel cell polyoma virus (MCV) are the main viruses associated with the development of cancer in immunosuppressed patients. Besides being a main cause of immunodeficiency, HIV1 has a direct pro-oncogenic effect. In this review, we provide an update on the association between the condition of acquired immunodeficiency and cancer risk, specifically addressing the contributions to oncogenesis of HPV, MCV, KSHV, HTLV-1, and EBV.

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Section: Human Herpes Virus-8 (Hhv-8)/kaposi's Sarcoma Herpes Virus (mentioning

confidence: 99%

Immunodeficiency-associated viral oncogenesis

Pierangeli

Antonelli

Gentile

2015

Clinical Microbiology and Infection

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“…KSHV is causally linked to particular human cancers, including Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and plasmablastic multicentric Castleman's disease (1)(2)(3)(4)(5)(6)(7). Among human viruses, KSHV is most closely related to the Epstein-Barr virus (EBV), a tumorigenic gamma-1 herpesvirus known to be associated with lymphomas and nasopharyngeal carcinoma.…”

mentioning

confidence: 99%

Viral Bcl-2 Encoded by the Kaposi's Sarcoma-Associated Herpesvirus Is Vital for Virus Reactivation

Gelgor

Kalt

Bergson

et al. 2015

J Virol

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The Kaposi's sarcoma-associated herpesvirus (KSHV) open reading frame 16 (orf16) encodes a viral Bcl-2 (vBcl-2) protein which shares sequence and functional homology with the Bcl-2 family. Like its cellular homologs, vBcl-2 protects various cell types from apoptosis and can also negatively regulate autophagy. vBcl-2 is transcribed during lytic infection; however, its exact function has not been determined to date. By using bacterial artificial chromosome 16 (BAC16) clone carrying the full-length KSHV genome, we have generated recombinant KSHV mutants that fail to express vBcl-2 or express mCherry-tagged vBcl-2. We show that the vBcl-2 protein is expressed at relatively low levels during lytic induction and that a lack of vBcl-2 largely reduces the efficiency of KSHV reactivation in terms of lytic gene expression, viral DNA replication, and production of infectious particles. In contrast, the establishment of latency was not affected by the absence of vBcl-2. Our findings suggest an important role for vBcl-2 during initial phases of lytic reactivation and/or during subsequent viral propagation. Given the known functions of vBcl-2 in regulating apoptosis and autophagy, which involve its direct interaction with cellular proteins and thus require high levels of protein expression, it appears that vBcl-2 may have additional regulatory functions that do not depend on high levels of protein expression. IMPORTANCEThe present study shows for the first time the expression of endogenous vBcl-2 protein in KSHV-infected cell lines and demonstrates the importance of vBcl-2 during the initial phases of lytic reactivation and/or during its subsequent propagation. It is suggested that vBcl-2 has additional regulatory functions beyond apoptosis and autophagy repression that do not depend on high levels of protein expression. K aposi's sarcoma-associated herpesvirus (KSHV), also referred to as human herpesvirus 8 (HHV-8), is a gamma-2 herpesvirus. KSHV is causally linked to particular human cancers, including Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and plasmablastic multicentric Castleman's disease (1-7). Among human viruses, KSHV is most closely related to the Epstein-Barr virus (EBV), a tumorigenic gamma-1 herpesvirus known to be associated with lymphomas and nasopharyngeal carcinoma. Like all other herpesviruses, the infectious cycle of KSHV includes two alternative infection phases, latent and lytic. Latent infection allows the virus to establish long-term persistent infection and involves the presence of viral episomes and expression of a small set of viral genes. Lytic infection is needed for the maintenance of viral reservoirs and for virus spread and involves a temporally regulated cascade of viral gene expression and DNA replication, leading to the production and release of new virions. KSHV exists mainly in its latent form in KS lesions and in PEL, yet a small subpopulation of cells undergoes lytic replication. Analogously, most KSHV-infected cultured cells are latently infected. Lytic virus react...

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“…Although most herpesvirus infections are self-limiting, they can lead to severe complications, particularly in immunocompromised patients (4 -9). Furthermore, gammaherpesvirus infections have been associated with cancer development (10,11).…”

mentioning

confidence: 99%

Global Mapping of O-Glycosylation of Varicella Zoster Virus, Human Cytomegalovirus, and Epstein-Barr Virus

Bagdonaite

Nordén

Joshi

et al. 2016

Journal of Biological Chemistry

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Herpesviruses are among the most complex and widespread viruses, infection and propagation of which depend on envelope proteins. These proteins serve as mediators of cell entry as well as modulators of the immune response and are attractive vaccine targets. Although envelope proteins are known to carry glycans, little is known about the distribution, nature, and functions of these modifications. This is particularly true for O-glycans; thus we have recently developed a "bottom up" mass spectrometry-based technique for mapping O-glycosylation sites on herpes simplex virus type 1. We found wide distribution of O-glycans on herpes simplex virus type 1 glycoproteins and demonstrated that elongated O-glycans were essential for the propagation of the virus. Here, we applied our proteome-wide discovery platform for mapping O-glycosites on representative and clinically significant members of the herpesvirus family: varicella zoster virus, human cytomegalovirus, and Epstein-Barr virus. We identified a large number of O-glycosites distributed on most envelope proteins in all viruses and further demonstrated conserved patterns of O-glycans on distinct homologous proteins. Because glycosylation is highly dependent on the host cell, we tested varicella zoster virus-infected cell lysates and clinically isolated virus and found evidence of consistent O-glycosites. These results present a comprehensive view of herpesvirus O-glycosylation and point to the widespread occurrence of O-glycans in regions of envelope proteins important for virus entry, formation, and recognition by the host immune system. This knowledge enables dissection of specific functional roles of individual glycosites and, moreover, provides a framework for design of glycoprotein vaccines with representative glycosylation.

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The role of Kaposi sarcoma‐associated herpesvirus in the pathogenesis of Kaposi sarcoma

Cited by 94 publications

References 155 publications

Immunodeficiency-associated viral oncogenesis

Immunodeficiency-associated viral oncogenesis

Viral Bcl-2 Encoded by the Kaposi's Sarcoma-Associated Herpesvirus Is Vital for Virus Reactivation

Global Mapping of O-Glycosylation of Varicella Zoster Virus, Human Cytomegalovirus, and Epstein-Barr Virus

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