Distinct Profiles of Antibodies to Kaposi Sarcoma–Associated Herpesvirus Antigens in Patients with Kaposi Sarcoma, Multicentric Castleman Disease, and Primary Effusion Lymphoma

Burbelo, Peter D.; Issa, Alexandra T.; Ching, Kathryn H.; Wyvill, Kathleen M.; Little, Richard F.; Iadarola, Michael J.; Kovacs, Joseph A.; Yarchoan, Robert

doi:10.1086/652869

Cited by 36 publications

(36 citation statements)

References 13 publications

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“…Combination treatment strategies with Nutlin-3 may lead to the elimination of both latent and lytic subsets of infected cells. 69 Berlin, Germany), 2 mM L-glutamine at 37 1C and 8.5% CO 2 . For reverse transfection of HEK 293 cells, 100 U/ml penicillin and 100 mg/ml streptomycin (both from PAA Laboratories) were added to the medium.…”

Section: Discussionmentioning

confidence: 99%

Structural proteins of Kaposi’s sarcoma-associated herpesvirus antagonize p53-mediated apoptosis

et al. 2014

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The tumor suppressor p53 is a central regulatory molecule of apoptosis and is commonly mutated in tumors. Kaposi's sarcoma-associated herpesvirus (KSHV)-related malignancies express wild-type p53. Accordingly, KSHV encodes proteins that counteract the cell death-inducing effects of p53. Here, the effects of all KSHV genes on the p53 signaling pathway were systematically analyzed using the reversely transfected cell microarray technology. With this approach we detected eight KSHV-encoded genes with potent p53 inhibiting activity in addition to the previously described inhibitory effects of KSHV genes ORF50, K10 and K10.5. Interestingly, the three most potent newly identified inhibitors were KSHV structural proteins, namely ORF22 (glycoprotein H), ORF25 (major capsid protein) and ORF64 (tegument protein). Validation of these results with a classical transfection approach showed that these proteins inhibited p53 signaling in a dose-dependent manner and that this effect could be reversed by small interfering RNA-mediated knockdown of the respective viral gene. All three genes inhibited p53-mediated apoptosis in response to Nutlin-3 treatment in non-infected and KSHV-infected cells. Addressing putative mechanisms, we could show that these proteins could also inhibit the transactivation of the promoters of apoptotic mediators of p53 such as BAX and PIG3. Altogether, we demonstrate for the first time that structural proteins of KSHV can counteract p53-induced apoptosis. These proteins are expressed in the late lytic phase of the viral life cycle and are incorporated into the KSHV virion. Accordingly, these genes may inhibit cell death in the productive and in the early entrance phase of KSHV infection.

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Section: Discussionmentioning

confidence: 99%

Structural proteins of Kaposi’s sarcoma-associated herpesvirus antagonize p53-mediated apoptosis

et al. 2014

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“…The pathophysiology of KS progression in the setting of rituximab is poorly understood but may be caused in part by the effects on KSHV-specific humoral immunity. [36][37][38][39][40] Also, rituximab alone may sometimes be inadequate in severe KSHV-MCD. [41][42][43] We combined rituximab with liposomal doxorubicin (R-Dox) with the rationale that liposomal doxorubicin would directly target CD20 -KSHV-infected MCD plasmablasts and KS spindle cells, including those in lymph nodes that may provide paracrine stimulation for KSHV-MCD plasmablasts.…”

Section: Introductionmentioning

confidence: 99%

Rituximab plus liposomal doxorubicin in HIV-infected patients with KSHV-associated multicentric Castleman disease

Uldrick

Polizzotto

Aleman

et al. 2014

Blood

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107

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“…Luciferase immunoprecipitation system (LIPS) technology has been applied to KSHV serology with considerable success. 31 A multiplex bead assay has also been recently developed by our lab. 32 Bead-based and other multiplexable assays have advantages over ELISAs.…”

Section: Kaposi Sarcoma-associated Herpesvirusmentioning

confidence: 99%

Serodiagnosis for Tumor Viruses

Morrison

Labò

Miley

et al. 2015

Seminars in Oncology

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The known human tumor viruses include the DNA viruses Epstein-Barr virus, Kaposi sarcoma herpesvirus, Merkel cell polyomavirus, human papillomavirus, and hepatitis B virus. RNA tumor viruses include Human T-cell lymphotrophic virus type-1 and hepatitis C virus. The serological identification of antigens/antibodies in plasma serum is a rapidly progressing field with utility for both scientists and clinicians. Serology is useful for conducting seroepidemiology studies and to inform on the pathogenesis and host immune response to a particular viral agent. Clinically, serology is useful for diagnosing current or past infection and for aiding in clinical management decisions. Serology is useful for screening blood donations for infectious agents and for monitoring the outcome of vaccination against these viruses. Serodiagnosis of human tumor viruses has improved in recent years with increased specificity and sensitivity of the assays, as well as reductions in cost and the ability to assess multiple antibody/antigens in single assays. Serodiagnosis of tumor viruses plays an important role in our understanding of the prevalence and transmission of these viruses and ultimately in the ability to develop treatments/preventions for these globally important diseases.

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Distinct Profiles of Antibodies to Kaposi Sarcoma–Associated Herpesvirus Antigens in Patients with Kaposi Sarcoma, Multicentric Castleman Disease, and Primary Effusion Lymphoma

Cited by 36 publications

References 13 publications

Structural proteins of Kaposi’s sarcoma-associated herpesvirus antagonize p53-mediated apoptosis

Structural proteins of Kaposi’s sarcoma-associated herpesvirus antagonize p53-mediated apoptosis

Rituximab plus liposomal doxorubicin in HIV-infected patients with KSHV-associated multicentric Castleman disease

Serodiagnosis for Tumor Viruses

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