Broad target cell selectivity of Kaposi's sarcoma-associated herpesvirus glycoprotein-mediated cell fusion and virion entry

Kaleeba, Johnan A.R.; Berger, Edward A.

doi:10.1016/j.virol.2006.06.009

Cited by 24 publications

(22 citation statements)

References 38 publications

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“…In vivo , KSHV has been detected in endothelial cells, epithelial cells, B cells, and monocytes (Ambroziak et al, 1995; Blasig et al, 1997; Dupin et al, 1999; Pauk et al, 2000), but in culture, the virus can infect a wider variety of cells including fibroblasts, keratinocytes, B lymphocytes, monocytes, plasmacytoid dendritic cells (pDCs), endothelial cells, and epithelial cells (Akula et al, 2003; Kaleeba & Berger, 2006a, 2006b; Lagunoff et al, 2002; Raghu, Sharma-Walia, Veettil, Sadagopan, & Chandran, 2009; Rappocciolo et al, 2008; Rappocciolo et al, 2006; Renne, Blackbourn, Whitby, Levy, & Ganem, 1998; West, Gregory, Sivaraman, Su, & Damania, 2011). …”

Section: Kshv Biology: Virion Transmission and Viral Lifecyclementioning

confidence: 99%

KSHV

Giffin

Damania

2014

Advances in Virus Research

116

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Kaposi’s sarcoma associated herpesvirus (KSHV; also known as human herpesvirus 8) is the etiological agent of Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. These cancers often occur in the context of immunosuppression, which has made KSHV-associated malignancies an increasing global health concern with the persistence of the AIDS epidemic. KSHV has also been linked to several acute inflammatory diseases. KSHV exists between a lytic and latent lifecycle which allow the virus to transition between active replication and quiescent infection. KSHV encodes a number of proteins and small RNAs that are thought to inadvertently transform host cells while performing their functions of helping the virus persist in the infected host. KSHV also has an arsenal of components that aid the virus in evading the host immune response, which help the virus establish a successful lifelong infection. In this comprehensive review, we will discuss the diseases associated with KSHV infection, the biology of latent and lytic infection, and individual proteins and microRNAs that are known to contribute to host cell transformation and immune evasion.

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Section: Kshv Biology: Virion Transmission and Viral Lifecyclementioning

confidence: 99%

KSHV

Giffin

Damania

2014

Advances in Virus Research

116

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“…Several proteins have been reported to serve as HHV-8 entry receptors (3,25,33). We have shown previously that DC-SIGN, a C-type lectin first identified on dendritic cells (DC) (18), is an entry receptor for HHV-8 on DC and macrophages in vitro (33).…”

mentioning

confidence: 99%

Human Herpesvirus 8 Infects and Replicates in Primary Cultures of Activated B Lymphocytes through DC-SIGN

Rappocciolo

Hensler

Jais

et al. 2008

J Virol

119

145

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Human herpesvirus 8 (HHV-8We hypothesized that the lack of permissive infection of B cells and B-cell lines with HHV-8 in vitro is related to the differential expression of the appropriate virus entry receptors. Several proteins have been reported to serve as HHV-8 entry receptors (3,25,33). We have shown previously that DC-SIGN, a C-type lectin first identified on dendritic cells (DC) (18), is an entry receptor for HHV-8 on DC and macrophages in vitro (33). DC-SIGN and its isomer DC-SIGNR were initially shown to be restricted in expression in vivo to dermal and lymphatic DC, activated macrophages, and vascular endothelial cells (38,40,44). Recent studies from our laboratory and others have demonstrated that B lymphocytes from peripheral blood and tonsils express DC-SIGN and that this expression significantly increases after B-cell activation mediated by CD40 ligand (CD40L) and interleukin 4 (IL-4) (22,34). These data suggest that DC-SIGN may also serve as an entry receptor on activated B (aB) cells and that its lack of expression on resting B (rB) cells may explain why previous attempts to infect B cells with HHV-8 have been had limited success.In the present study, we show that activated blood and tonsillar B cells expressing DC-SIGN can be productively infected with HHV-8, as determined by an increase in the level of viral DNA, the expression of lytic and latency-associated viral proteins, and the production of infectious virus. HHV-8 infection could be blocked by the pretreatment of the B cells with anti-DC-SIGN monoclonal antibody (MAb). These results are the first evidence of a fully productive infection of B cells and confirm the role of DC-SIGN as an entry receptor for this virus. This model can provide insight into the life cycle of HHV-8 and a better understanding of its pathogenesis.

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“…Even though KSHV does not replicate efficiently in cell lines, it can establish latent infection in a variety of adherent cell lines (4). However, B-cell lines appear to be among the most resistant cell lines (4,8,24,35). Even more striking, whereas numerous cell lines are highly permissive for the MHV68 productive cycle, B-cell lines are poorly infected.…”

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confidence: 99%

“…However, there are indications that, at least in the case of KSHV, there might be a block at the level of viral entry. Indeed, B-lymphoma cell lines were resistant in KSHV glycoprotein-mediated cell fusion and viral entry assays (24). Moreover, the transfection of the KSHV genome into B-lymphoma BJAB cells led to the establishment of latency (11).…”

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confidence: 99%

Lack of Heparan Sulfate Expression in B-Cell Lines: Implications for Kaposi's Sarcoma-Associated Herpesvirus and Murine Gammaherpesvirus 68 Infections

Jarousse

Chandran

Coscoy

2008

J Virol

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Kaposi's sarcoma-associated herpesvirus (KSHV) and its murine homolog, murine gammaherpesvirus 68 (MHV68), are lymphotropic viruses that establish latent infection in their host. Surprisingly, while B cells are the main viral reservoir in vivo, B-cell lines are poorly permissive to infection by either MHV68 or KSHV. Here, we report that most B-cell lines express very little to no cell surface heparan sulfate (HS), a glycosaminoglycan that is essential for infection by these viruses. We found that Ext1, a key enzyme in the biosynthesis of HS, was expressed at a low level in these cells. Transfection of B-cell lines with Ext1 restored high HS expression at the cell surface. Overexpression of Ext1 in murine A20 and M12 B-cell lines increased MHV68 surface binding and enhanced the efficiency of infection. Finally, although it was not sufficient to allow efficient infection, the expression of HS on BJAB cells promoted KSHV binding at the cell surface. Thus, our results indicate that MHV68 and KSHV cycles are blocked in B-cell lines at the binding step due to a lack of surface HS.One of the characteristics of gammaherpesviruses is their tropism for B lymphocytes, where they establish latency (i.e., limited viral gene expression) and persist during the whole life of their host. Kaposi's sarcoma-associated herpesvirus (KSHV, also known as human herpesvirus 8) is a gammaherpesvirus associated with both lymphoid and nonlymphoid cell tumors in humans, mostly in immunodeficient patients. KSHV is the etiologic agent of Kaposi's sarcoma, an AIDS-associated skin cancer, as well as B-cell lymphoproliferative disorders such as primary effusion lymphoma and Castleman disease (9, 10, 39). Studies of KSHV are limited by the lack of cell lines able to support productive infection as well as the strict restriction in host range. Murine gammaherpesvirus 68 (MHV68) is phylogenetically related to KSHV (13,48). MHV68 infects mice, where it establishes latency mostly in B cells (15,16,42), and has been associated with lymphoproliferative diseases in longterm-infected mice (41) or immunodeficent mice (44). Moreover, unlike KSHV, MHV68 replicates efficiently in vitro in different fibroblast and epithelial cell lines. Thus, MHV68 provides a small-animal model for the analysis of gammaherpesvirus pathogenesis both in vitro and in vivo (37,40,47).Researchers in the field have been puzzled by the fact that while B cells are the main viral reservoir in vivo, B-cell lines are mostly resistant to infection by KSHV and MHV68. Even though KSHV does not replicate efficiently in cell lines, it can establish latent infection in a variety of adherent cell lines (4). However, B-cell lines appear to be among the most resistant cell lines (4,8,24,35). Even more striking, whereas numerous cell lines are highly permissive for the MHV68 productive cycle, B-cell lines are poorly infected. MHV68 viral transcript (orf73) could be detected by reverse transcription (RT)-PCR (17) or real-time RT-PCR (unpublished observations) after infection of the A20 murine B-cel...

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Broad target cell selectivity of Kaposi's sarcoma-associated herpesvirus glycoprotein-mediated cell fusion and virion entry

Cited by 24 publications

References 38 publications

KSHV

KSHV

Human Herpesvirus 8 Infects and Replicates in Primary Cultures of Activated B Lymphocytes through DC-SIGN

Lack of Heparan Sulfate Expression in B-Cell Lines: Implications for Kaposi's Sarcoma-Associated Herpesvirus and Murine Gammaherpesvirus 68 Infections

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