Inefficient establishment of KSHV latency suggests an additional role for continued lytic replication in Kaposi sarcoma pathogenesis

Grundhoff, Adam; Ganem, Don

doi:10.1172/jci17803

Cited by 226 publications

(252 citation statements)

References 71 publications

(26 reference statements)

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“…This seemed to be due to the specific elimination of KSHV-infected cells and outgrowth of uninfected cells since the major latency associated protein LANA-1 was expressed in approximately 70% of untreated cells, whereas only 8% of cell expressed LANA-1 in cells treated with 50 mM HNMPA-(AM 3 ) for 14 days (Figure 4b). Alternatively, it is also conceivable that KSHV-genomes were lost from HNMPA-treated cultures as described for other endothelial cell lines (Grundhoff and Ganem, 2004).…”

Section: Resultsmentioning

confidence: 99%

The insulin receptor is essential for virus-induced tumorigenesis of Kaposi's sarcoma

Rose

Carroll

et al. 2006

Oncogene

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Section: Resultsmentioning

confidence: 99%

The insulin receptor is essential for virus-induced tumorigenesis of Kaposi's sarcoma

Rose

Carroll

et al. 2006

Oncogene

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“…LANA-1 is also thought to mediate the attachment of viral episomes to chromosomes during mitosis and to ensure thereby their segregation into daughter cells [90,93,94]. However, viral latent episomes are lost rapidly from infected cultured cells and the LANA-1-mediated retention of viral DNA therefore appears to be an inefficient process in most cells, including endothelial cells [95]. This also applies to short-term cultures of Kaposi biopsies which lose the KSHV viral DNA after a few passages in vitro [96].…”

Section: Kshv Latency and Latent Viral Genes In Ksmentioning

confidence: 99%

“…Only B-cell lines established from PEL samples retain KSHV genomes efficiently after prolonged in vitro culture in the absence of selection (detailed references in ref 97). After infection by KSHV of several endothelial and epithelial cell lines, a small subpopulation of these cells can also retain KSHV [95]. However, this is not a stable property of these cells and the rare successful retention of a viral genome may involve epigenetic mechanisms, which are, as yet, unknown [95].…”

Section: Kshv Latency and Latent Viral Genes In Ksmentioning

confidence: 99%

“…After infection by KSHV of several endothelial and epithelial cell lines, a small subpopulation of these cells can also retain KSHV [95]. However, this is not a stable property of these cells and the rare successful retention of a viral genome may involve epigenetic mechanisms, which are, as yet, unknown [95]. Whether the latent stage observed in the majority of KS spindle cells (see above and Figure 1) actually persists over a longer time, or whether KSHV needs to re-infect new endothelial cells continuously to persist over long time periods, is unclear at present [95].…”

Section: Kshv Latency and Latent Viral Genes In Ksmentioning

confidence: 99%

“…However, this is not a stable property of these cells and the rare successful retention of a viral genome may involve epigenetic mechanisms, which are, as yet, unknown [95]. Whether the latent stage observed in the majority of KS spindle cells (see above and Figure 1) actually persists over a longer time, or whether KSHV needs to re-infect new endothelial cells continuously to persist over long time periods, is unclear at present [95]. The recently reported observation that in some cases of transplant KS, the KS spindle cell was of donor origin is compatible with the notion that latently infected endothelial cells were transmitted along with the donor organ and then developed into KS spindle cells [98].…”

Section: Kshv Latency and Latent Viral Genes In Ksmentioning

confidence: 99%

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The pleiotropic effects of Kaposi's sarcoma herpesvirus

Schulz

2005

The Journal of Pathology

156

143

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Kaposi's sarcoma herpesvirus (KSHV), or human herpesvirus 8 (HHV8), is an essential factor in the pathogenesis of Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). Case reports suggest an occasional involvement in bone marrow hypoplasia and haemophagocytic syndrome, but other disease associations are unconfirmed or controversial. KSHV-associated disease is of particular importance in immunosuppressed individuals, in particular in patients with HIV infection and transplant recipients. KSHV establishes a latent infection in the majority of infected cells in KS, MCD, and PEL, but lytic replication occurs in a small fraction of infected cells. Viral proteins expressed during both the latent and the lytic phase of the viral life cycle contribute to the pathogenesis of KSHV-associated diseases.

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Mono/oligoclonal pattern of Kaposi Sarcoma‐associated herpesvirus (KSHV/HHV‐8) episomes in primary effusion lymphoma cells

Boulanger

Duprez

Delabesse

et al. 2005

Intl Journal of Cancer

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Primary effusion lymphoma (PEL) is a rare lymphoma of B‐cell origin, developed in serous cavities. PEL tumor cells are latently infected with Kaposi sarcoma‐associated herpesvirus (KSHV) and in most cases co‐infected with Epstein‐Barr virus (EBV). In 15 primary PEL tumors including 10 EBV‐positive cases, we analyzed the fused terminal repeat (TR) regions of KSHV episomes using pulsed‐field gel electrophoresis and Southern blot. On the same genomic DNA samples, the cellular clonality was assessed by Southern blot and PCR detection of monoclonal immunoglobulin heavy chain (IGH) VDJ gene rearrangements, associated in the EBV‐infected cases, with Southern blot analysis of the fused termini of EBV episomes. Monoclonal IGH gene rearrangements were detected in 13 tumors using Southern blot, in 11 cases using PCR, and in all cases considering both methods. EBV infection was monoclonal in all EBV‐positive cases. However, only 5 PEL tumors were found to be monoclonally infected with KSHV. In the 10 other cases, we found a biclonal (2 bands; n = 4) or an oligoclonal pattern (3–6 bands; n = 6) of KSHV episomes. We hypothesized that the apparent discrepancy between viral and cellular clonalities in PEL might be due to several phenomena including complex mechanisms of genomic recircularization, insertion of duplicated sequences into the TR region and simultaneous infection of tumor cells with defective KSHV variants. KSHV infection of contaminating nontumoral cells, superinfection from lytically infected cells or viral integration events might also explain the oligoclonal pattern of KSHV infection. Several of these mechanisms, not mutually exclusive, might coexist in a single tumor. © 2005 Wiley‐Liss, Inc.

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Inefficient establishment of KSHV latency suggests an additional role for continued lytic replication in Kaposi sarcoma pathogenesis

Cited by 226 publications

References 71 publications

The insulin receptor is essential for virus-induced tumorigenesis of Kaposi's sarcoma

The insulin receptor is essential for virus-induced tumorigenesis of Kaposi's sarcoma

The pleiotropic effects of Kaposi's sarcoma herpesvirus

Mono/oligoclonal pattern of Kaposi Sarcoma‐associated herpesvirus (KSHV/HHV‐8) episomes in primary effusion lymphoma cells

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