Pathogenesis of Kaposi's sarcoma

Bubman, Darya; Cesarman, Ethel

doi:10.1016/s0889-8588(03)00044-3

Cited by 41 publications

(44 citation statements)

References 199 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several studies implicate the chemokine receptor vGPCR in the pathogenesis of KS (19)(20)(21). Expression of this molecule in transgenic mice leads to development of a disease that resembles KS both clinically and histologically (9)(10)(11)(12).…”

Section: Discussionmentioning

confidence: 99%

The human herpesvirus 8 chemokine receptor vGPCR triggers autonomous proliferation of endothelial cells

Grisotto

Garin²,

Martín³

et al. 2006

Journal of Clinical Investigation

View full text Add to dashboard Cite

We have used a novel conditional transgenic system to study the mechanisms of angioproliferation induced by viral G protein-coupled receptor (vGPCR), the constitutively active chemokine receptor encoded by human herpesvirus 8 (HHV8, also known as Kaposi sarcoma herpesvirus). Using this system, we were able to control temporal expression of vGPCR and to monitor its expression in situ via the use of the surrogate marker LacZ. Our lab and others have shown that transgenic expression of viral G protein-coupled receptor (vGPCR), the chemokine receptor encoded by HHV8 ORF74, induces development of angioproliferative lesions that resemble those seen in KS (9-11). In our model, the lesions are observed in ears, limbs, and tail and progress from erythematous lesions to nodules and tumors within 6 months (9). The lesions are composed of large numbers of spindleshaped CD34 + cells, vascular channels, and inflammatory cells. Conditional expression of vGPCR triggers expression of several angiogenic factors in lesional areas, and its inactivation results in regression of the angioproliferative lesions (12).

show abstract

Section: Discussionmentioning

confidence: 99%

The human herpesvirus 8 chemokine receptor vGPCR triggers autonomous proliferation of endothelial cells

Grisotto

Garin²,

Martín³

et al. 2006

Journal of Clinical Investigation

View full text Add to dashboard Cite

show abstract

“…HHV-8 has been detected in KS spindle cells, which are of mixed vascular and lymphatic endothelial cell and macrophage origin (2), and monocytes that are found in proximity to KS lesions (3). Virus persists in a latent form in these cell types as well as in B lymphocytes.…”

mentioning

confidence: 99%

DC-SIGN Is a Receptor for Human Herpesvirus 8 on Dendritic Cells and Macrophages

Rappocciolo¹,

Jenkins²,

Hensler³

et al. 2006

The Journal of Immunology

179

201

View full text Add to dashboard Cite

Human herpesvirus 8 (HHV-8) causes Kaposi’s sarcoma and pleural effusion lymphoma. In this study, we show that dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN; CD209) is a receptor for HHV-8 infection of myeloid DCs and macrophages. DC-SIGN was required for virus attachment to these cells and DC-SIGN-expressing cell lines. HHV-8 binding and infection were blocked by anti-DC-SIGN mAb and soluble DC-SIGN, and mannan, a natural ligand for DC-SIGN. Infection of DCs and macrophages with HHV-8 led to production of viral proteins, with little production of viral DNA, similar to HHV-8 infection of vascular endothelial cells. Infection of DCs resulted in down-regulation of DC-SIGN, a decrease in endocytic activity, and an inhibition of Ag stimulation of CD8+ T cells. We propose that DC-SIGN serves as a portal for immune dysfunction and oncogenesis caused by HHV-8 infection.

show abstract

“…In the absence of a culture system derived from KS tumorassociated cell lines to allow direct demonstration of KSHV (2,18), the diagnosis of KSHV infection has relied on molecular techniques and the use of serological assays to detect antibodies to KSHV antigens produced during latent or lytic phases of the viral life cycle (13,15,26). The immunofluorescence assay to detect anti-LANA antibodies (IFA-LANA) has long been considered a reference serological test to detect KSHV infection (23).…”

mentioning

confidence: 99%

Comparative Study of Kaposi's Sarcoma-Associated Herpesvirus Serological Assays Using Clinically and Serologically Defined Reference Standards and Latent Class Analysis

et al. 2007

View full text Add to dashboard Cite

Accurate determination of infection with Kaposi's sarcoma-associated herpesvirus (KSHV) has been hindered by the lack of a "gold standard" for comparison of serological assays used to estimate KSHV prevalence in serosurveys conducted in different settings. We have evaluated the performance of five in-house (developed at University College London [UCL], United Kingdom, and at the virology laboratory of the Instituto de Medicine Tropical [IMT] in Sao Paulo, Brazil) and two commercial (ABI and DIAVIR) serological assays to detect antibodies to latency-associated nuclear antigen (LANA) and to lytic KSHV antigens. We used a variety of serum samples assembled to represent populations likely to be at high, intermediate, and low risk of KSHV infection in Brazil. Composite reference standard panels were prepared based on clinical and serological parameters, against which assay performances were assessed using conventional Bayesian statistics and latent class analysis (LCA). Against the clinical reference standard, in-house immunofluorescence assays to detect anti-LANA antibodies (IFA-LANA) produced at UCL and IMT had similar performances, with sensitivities of 61% (95% confidence interval [CI], 48% to 74%) and 72% (95% CI, 58% to 83%) and specificities of 99% (95% CI, 94% to 100%) and 100% (95% CI, 96% to 100%), respectively, and only the IMT IFA-LANA was included in LCA, together with the IMT IFA-lytic and four enzyme-linked immunosorbent assays (ELISAs). The LCA indicated that the IMT whole-virus ELISA performed best (sensitivity, 87% [95% CI, 81% to 91%]; and specificity, 100% [95% CI, 98% to 100%]), confirming the results obtained with the conventional statistical approach. Commercially available ELISA-based tests yielded the lowest specificities using a spectrum of serum samples. The evaluation of KSHV serological assays is warranted before planning serosurveys in various settings.

show abstract

Pathogenesis of Kaposi's sarcoma

Cited by 41 publications

References 199 publications

The human herpesvirus 8 chemokine receptor vGPCR triggers autonomous proliferation of endothelial cells

The human herpesvirus 8 chemokine receptor vGPCR triggers autonomous proliferation of endothelial cells

DC-SIGN Is a Receptor for Human Herpesvirus 8 on Dendritic Cells and Macrophages

Comparative Study of Kaposi's Sarcoma-Associated Herpesvirus Serological Assays Using Clinically and Serologically Defined Reference Standards and Latent Class Analysis

Contact Info

Product

Resources

About