Blood Dendritic Cells From Myeloma Patients Are Not Infected With Kaposi's Sarcoma-Associated Herpesvirus (KSHV/HHV-8)

Yi, Qing; Ekman, Martin; Anton, Doina; Bergenbrant, Susanne; Österborg, Anders; Georgii-Hemming, Patrik; Holm, G.; Nilsson, Kenneth; Biberfeld, Peter

doi:10.1182/blood.v92.2.402

Cited by 49 publications

(6 citation statements)

References 13 publications

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“…These results reaffirm that our findings are not due to contamination or due to artifacts. In contrast to our results and those of others, many investigators have failed to detect the KSHV DNA in BM biopsies or in BM dendritic cell cultures in MM patients 9–16. These contrasting results may be attributable to differences in PCR methodology and in the sensitivity of the techniques used.…”

Section: Discussioncontrasting

confidence: 99%

“…Two additional independent laboratories confirmed the presence of KSHV DNA sequences in MM biopsies 7, 8. However, other groups have not been able to confirm this association either in bone marrow (BM) biopsies or in dendritic cell cultures from either the BM or peripheral blood 9–14. All of these conflicting results are based on findings in MM patients from western countries.…”

mentioning

confidence: 99%

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Detection of Kaposi sarcoma-associated herpesvirus in bone marrow biopsy samples from patients with multiple myeloma

Hsu

Lee

Yang

et al. 2001

Cancer

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BACKGROUND Kaposi sarcoma‐associated herpesvirus (KSHV) recently has been identified in the bone marrow (BM) dendritic cell of multiple myeloma (MM) patients. However, whether or not KSHV is associated with MM remains controversial because many studies have failed to detect the presence of KSHV DNA sequences in the BM of their MM patients. METHODS We have assayed for KSHV DNA sequences in the BM biopsy samples from 49 patients with MM and from 8 patients with normal BM, using nested polymerase chain reaction and dot blot analysis. The polymerase chain reaction product of KSHV was further determined by single‐strand conformation polymorphism and sequence analyses. RESULTS KSHV DNA was detectable in 22 of 49 patients (44.9%) with MM but was not detectable in normal BM cells. Single‐strand conformation polymorphism and sequence analyses showed that there were interpatient specific mutations. Sixteen out of 22 KSHV DNA sequences belonged to a previously defined subgroup, and the other 6 remain unclassified and may represent distinct strains of KSHV in Taiwan. CONCLUSIONS Data strongly supported that KSHV infection did exist in the BM of the current study patients with MM. However, the role of KSHV in the pathogenesis of multiple myeloma remains to be determined. Cancer 2001;91:1409–13. © 2001 American Cancer Society.

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Section: Discussioncontrasting

confidence: 99%

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confidence: 99%

Detection of Kaposi sarcoma-associated herpesvirus in bone marrow biopsy samples from patients with multiple myeloma

Hsu

Lee

Yang

et al. 2001

Cancer

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“…Differences in the experimental strategy adopted cannot explain the discrepancy observed between the current investigation and the studies reporting a positive association between AIDS-PCNSL and HHV-8/KSHV (11,33). At present, the reasons for such discrepancy are unclear and may be of multiple nature, as recently exemplified by the discrepancies among studies on the relationship between HHV-8/KSHV and multiple myeloma (29,32,42,44,48,51). Hovewer, independ-ently of the precise reasons accounting for the observed discrepancies, it should be stressed that defining a positive association between a tumor and a virus based solely on the results of high sensitivity molecular assays, in the absence of serological evidence, may be misleading (36).…”

Section: Discussioncontrasting

confidence: 59%

HHV‐8/KSHV is Not Associated with AIDS‐Related Primary Central Nervous System Lymphoma

et al. 1999

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Primary central nervous system lymphoma (PCNSL) is a major complication of the late stages of human immunodeficiency virus (HIV) disease. Epstein Barr virus (EBV) infection is the only genetic lesion consistently associated with this neoplasia. Recently, it has been proposed that the pathogenesis of AIDS‐related PCNSL (AIDS‐PCNSL) may be associated with infection by human herpesvirus‐8/Kaposi's sarcoma associated herpesvirus (HHV‐8/KSHV), although at present such association remains controversial. In order to conclusively assess the link between HHV‐8/KSHV infection and AIDS‐PCNSL, we performed a comprehensive study based on multiple molecular assays on cerebral tissues and cerebrospinal fluid (CSF) as well as specific immunologic assays on patients’ sera. A well characterized panel of 33 Italian patients with AIDS‐PCNSL and 13 controls with other HIV‐related brain focal diseases from the same geographical area was analyzed. No signs of HHV‐8/KSHV infection were detected in cerebral tissues by single‐step PCR. Cerebral tissues of all AIDS‐PCNSL scored negative for HHV‐8/KSHV DNA sequences also by nested PCR, with the exception of one single patient who was simultaneously affected by Kaposi's sarcoma. All CSF samples analyzed were consistently devoid of HHV‐8/KSHV sequences by molecular assays. By serologic assays, detecting both latent and lytic HHV‐8/KSHV antigens, a specific immunoreactivity was observed in 16/33 (48%) AIDS‐PCNSL and in 6/13 (46%) controls (P=0.88). A significant correlation with HHV‐8/KSHV serum reactivity was seen with a homosexual route of HIV transmission (P=0.018), but not with the presence of AIDS‐PCNSL. The results of our analysis conclusively assess that HHV‐8/KSHV infection is not a feature of AIDS‐PCNSL.

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“…HHV-8 infection was initially found in bone marrow DC of patients with multiple myeloma ( Rettig et al, 1997 ). However, evidence since has concluded that bone marrow-derived ( Mitterer et al, 1998 ), peripheral blood mononuclear cell (PBMC)-derived ( Cull et al, 1998 ; Yi et al, 1998 ), and CD34 positive cell-derived ( Mitterer et al, 1998 ) DC from myeloma patients do not contain HHV-8 sequences. In fact, the absence of HHV-8 in DC of these patients increases the feasibility of an autologous, DC-based immunomodulatory therapy for multiple myeloma.…”

Section: In Hhv-8-associated Diseasementioning

confidence: 99%

Dendritic cells: key players in human herpesvirus 8 infection and pathogenesis

et al. 2014

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Human herpesvirus 8 (HHV-8; Kaposi's sarcoma-associated herpesvirus) is an oncogenic gammaherpesvirus that primarily infects cells of the immune and vascular systems. HHV-8 interacts with and targets professional antigen presenting cells and influences their function. Infection alters the maturation, antigen presentation, and immune activation capabilities of certain dendritic cells (DC) despite non-robust lytic replication in these cells. DC sustains a low level of antiviral functionality during HHV-8 infection in vitro. This may explain the ability of healthy individuals to effectively control this virus without disease. Following an immune compromising event, such as organ transplantation or human immunodeficiency virus type 1 infection, a reduced cellular antiviral response against HHV-8 compounded with skewed DC cytokine production and antigen presentation likely contributes to the development of HHV-8 associated diseases, i.e., Kaposi's sarcoma and certain B cell lymphomas. In this review we focus on the role of DC in the establishment of HHV-8 primary and latent infection, the functional state of DC during HHV-8 infection, and the current understanding of the factors influencing virus-DC interactions in the context of HHV-8-associated disease.

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Blood Dendritic Cells From Myeloma Patients Are Not Infected With Kaposi's Sarcoma-Associated Herpesvirus (KSHV/HHV-8)

Cited by 49 publications

References 13 publications

Detection of Kaposi sarcoma-associated herpesvirus in bone marrow biopsy samples from patients with multiple myeloma

Detection of Kaposi sarcoma-associated herpesvirus in bone marrow biopsy samples from patients with multiple myeloma

HHV‐8/KSHV is Not Associated with AIDS‐Related Primary Central Nervous System Lymphoma

Dendritic cells: key players in human herpesvirus 8 infection and pathogenesis

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