Utilization of human hematopoietic cell lines for the propagation and characterization of HBLV (human herpesvirus 6)

Ablashi, Dharam V.; Lusso, Paolo; Hung, Chia Chun; Salahuddin, S. Z.; Josephs, Steven F.; Llana, T; Kramarsky, Bernhard; Biberfeld, Peter; Markham, Phillip D.; Gallo, Robert C.

doi:10.1002/ijc.2910420526

Cited by 137 publications

(55 citation statements)

References 18 publications

(4 reference statements)

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“…[11][12][13][14][15] In the present report, we describe two cases of immunocompetent adults who presented with fever and generalized lymphadenopathy, and on biopsy were found to have viral lymphadenitis with massive numbers of viral inclusions in CD4-positive T lymphocytes. The presence of the virus in these cells was confirmed by immunohistochemistry, and electron microscopy and molecular studies identified distinctive features of HHV-6B.…”

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confidence: 74%

Human herpesvirus-6-associated acute lymphadenitis in immunocompetent adults

et al. 2004

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In contrast to other causes of herpetic lymphadenitis, the histological features associated with human herpesvirus-6 (HHV-6) infection have remained elusive since its discovery in 1986. We describe the histologic and phenotypic changes associated with acute HHV-6 lymphadenitis in two immunocompetent adults who presented with fever, fatigue, generalized lymphadenopathy, and elevated liver enzymes. Serologic tests for human immunodeficiency virus, acute Epstein-Barr virus, and cytomegalovirus infection were negative. Lymph node biopsies were consistent with viral lymphadenitis. Intranuclear and cytoplasmic inclusions were identified in CD4-positive T lymphocytes in expanded paracortical areas. Immunohistochemical staining with monoclonal antibody to the HHV-6 gp60/110 kDa envelope glycoprotein showed that the inclusions were positive for viral antigen. Electron microscopy demonstrated numerous viral particles in the cytoplasm and nucleus, characteristic of Herpesviridae family. Clustering of viral particles was observed, which has previously been reported only in infected tissue culture cells. PCR followed by sequencing of DNA extracted from the lymph nodes identified the virus as HHV-6, type B. This is the first report that documents distinctive histologic features of HHV-6 lymphadenitis and demonstrates that the cells harboring the virus in vivo are CD4-positive T lymphocytes.

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confidence: 74%

Human herpesvirus-6-associated acute lymphadenitis in immunocompetent adults

et al. 2004

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“…Cultures were kept for three days and were pulsed with [methyl-3 H]thymidine (Amersham) at 1 Ci per well during the last 16 h of culture. Cells were then harvested with an automated cell harvester (Tomtec, Orange, Conn.), and [methyl- 3 H]thymidine incorporation was measured in a Microbeta Trilux counter (Wallac, Turku, Finland). A well or culture was defined as specific for the corresponding antigen when the counts per minute were greater than 1,500 and exceeded the reference counts per minute (in the absence of the antigen) by at least three times.…”

Section: Methodsmentioning

confidence: 99%

“…Only HHV-6B has been definitively proven to cause human disease (44,49). HHV-6 also has a neurotropic property (3) and was found to cause subacute leukoencephalitis, manifesting as MS and demyelination of the central nervous system (8,19). Epidemiologic studies have shown that the vast majority of primary HHV-6 infections occur within the first year of life (13,50).…”

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confidence: 99%

Detection of Viral DNA and Immune Responses to the Human Herpesvirus 6 101-Kilodalton Virion Protein in Patients with Multiple Sclerosis and in Controls

Tejada‐Simon

Zang

Hong

et al. 2002

J Virol

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Human herpesvirus 6 (HHV-6), a latent lymphotropic and neurotropic virus, has been suspected as an etiologic agent in multiple sclerosis (MS). The study was undertaken to correlate virologic evidence for HHV-6 activity with the state of host immunity to HHV-6 in MS patients and control subjects. The study revealed that cell-free DNA of HHV-6 was detected more frequently in both serum and cerebrospinal fluid of MS patients than in those of control subjects. T cells recognizing the recombinant 101-kDa protein (101K) corresponding to the major immunoreactive region unique to HHV-6 occurred at significantly lower precursor frequency in MS patients than in control subjects. The resulting HHV-6-specific T-cell lines obtained from MS patients exhibited skewed cytokine profiles characterized by the inability to produce interleukin-4 (IL-4) and IL-10. The decreased T-cell responses to HHV-6 and the altered cytokine profile were consistent with significantly declined serum immunoglobulin G (IgG) titers for HHV-6 of MS patients compared to those of control subjects. In contrast, elevated serum IgM titers for HHV-6 were detected in the majority of MS patients, which may reflect frequent exposure of B cells to HHV-6. The findings suggest that the decreased immune responses to HHV-6 may be responsible for ineffective clearance of HHV-6 in MS patients.

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“…However, it is now well known that HHV-6 exhibits tropism mainly for T lymphocytes and monocytes/macrophages and that various kinds of cells, including myeloid precursor cells, megakaryocytes, natural killer cells, fibroblasts, astrocytes, and hepatoma cells, are also susceptible to HHV-6 infection (1,15,18,19,22). Various immunobiological alterations of T lymphocytes have been observed following infection with HHV-6.…”

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confidence: 99%

Phenotypic and Functional Alterations of Dendritic Cells Induced by Human Herpesvirus 6 Infection

Kakimoto

Hasegawa

Fujita

et al. 2002

J Virol

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Human herpesvirus 6 (HHV-6) has a tropism for T lymphocytes and monocytes/macrophages, suggesting that HHV-6 infection affects the immunosurveillance system. In the present study, we investigated the HHV-6-induced phenotypic and functional alterations of dendritic cells (DCs), which are professional antigenpresenting cells. HHV-6 infection of monocyte-derived immature DCs appeared to induce the up-regulation of CD80, CD83, CD86, and HLA class I and class II molecules, suggesting that HHV-6 infection induces the maturation of DCs. In addition, the antigen capture capacity of DCs was found to decrease following infection with HHV-6. In contrast to up-regulation of mature-DC-associated surface molecules on HHV-6-infected DCs, their capacity for presentation of alloantigens and exogenous virus antigens to T lymphocytes decreased significantly from that of uninfected DCs. In contrast, there appeared to be no reduction in the capacity for presentation of an HLA class II-binding peptide to the peptide-specific CD4 ؉ T lymphocytes. These data indicate that HHV-6 infection induces phenotypic alterations and impairs the antigen presentation capacity of DCs. The present data also suggest that the dysfunction of HHV-6-infected DCs is attributable mainly to impairment of the antigen capture and intracellular antigen-processing pathways.

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Utilization of human hematopoietic cell lines for the propagation and characterization of HBLV (human herpesvirus 6)

Cited by 137 publications

References 18 publications

Human herpesvirus-6-associated acute lymphadenitis in immunocompetent adults

Human herpesvirus-6-associated acute lymphadenitis in immunocompetent adults

Detection of Viral DNA and Immune Responses to the Human Herpesvirus 6 101-Kilodalton Virion Protein in Patients with Multiple Sclerosis and in Controls

Phenotypic and Functional Alterations of Dendritic Cells Induced by Human Herpesvirus 6 Infection

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