Disease relevance of Herpesvirus 6, Human

• Recently, human herpesvirus 6 (HHV-6), a newly described beta-herpes virus that shares homology with cytomegalovirus (CMV), has been reported to be present in active MS plaques [1].
• Increased HIV-1 LTR directed gene expression is obtained in HIV-1 infected cells co-infected with HHV-6, or in HHV-6 infected cells co-transfected with the HIV-1 tat gene [2].
• To determine the distribution of HHV-7-infected cells relative to those infected with HHV-6, sections from paraffin-embedded tissues were allowed to react with antibodies to HHV-7 virion tegument phosphoprotein pp85 and to HHV-6B protein p101 [3].
• Cross-reactivity with myelin basic protein and human herpesvirus-6 in multiple sclerosis [4].
• To investigate this point, we evaluated the presence and distribution of HHV-6 DNA by Southern blot, nested polymerase chain reaction, and in situ hybridization in a series of lymphoproliferative disorders including 73 Hodgkin's disease cases, 15 non-Hodgkin lymphomas, and 19 reactive lymph nodes [5].

Psychiatry related information on Herpesvirus 6, Human

• Our results demonstrate that undifferentiated HM were highly resistant to HHV-6 infection, whereas HM pretreated with human recombinant IL-15 showed an increased permissiveness for HHV-6 infection [6].

High impact information on Herpesvirus 6, Human

• CD46 is a cellular receptor for human herpesvirus 6 [7].
• Given the ubiquitous nature of this virus and the challenging precedent of correlating antiviral antibodies with disease association, these antibody studies have been supported by the detection of HHV-6 DNA from samples of MS serum as a marker of active viral infection [1].
• In addition to fresh T cells, HBLV was able to infect normal T lymphocytes expanded in vitro with IL-2 for greater than 30 d [8].
• IL-15 protein synthesis was increased in response to HHV-6 [9].
• Furthermore, NK activation by HHV-6 was blocked with mAb to CD122, as well as by human anti-HHV-6 neutralizing antibodies [9].

Chemical compound and disease context of Herpesvirus 6, Human

• Susceptibility of human herpesvirus 6 to acyclovir and ganciclovir [10].
• Susceptibility of human herpesvirus 6 to acyclovir [11].
• Exposure of human macrophages to HHV-6A or HHV-6B profoundly impaired their ability to produce interleukin 12 (IL-12) upon stimulation with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) [12].
• Expression of the immediate early or early genes of HHV-6 was not sufficient to induce CD3/TCR modulation, as indicated by studies with the viral DNA polymerase inhibitor phosphonoformic acid [13].
• We mapped the different promoter elements associated with COX-2 gene activation by HHV-6 to two cis-acting elements: a cyclic AMP-responsive element and an activator protein-1 element [14].

Biological context of Herpesvirus 6, Human

• Downregulation of surface CD46 was documented during the course of HHV-6 infection [7].
• These findings are consistent with the hypothesis that the U94 gene product of HHV-6 regulates viral gene expression and enables the establishment and/or maintenance of latent infection in lymphoid cells [15].
• Two sensitive polymerase chain reaction assays were used to target different regions within the HHV-6 genome [16].
• During the course of HHV-6 infection, analysis of the surface membrane phenotype of the T cell populations and clones revealed a progressive decline in the expression of the CD3/TCR complex, whereas other T cell-associated markers (e.g., CD2) were unaffected [13].
• We employed a quantitative cell fusion assay to identify structural domains of CD46 required for its function as a receptor for human herpesvirus 6 (HHV-6) [17].

Anatomical context of Herpesvirus 6, Human

• Primary cell culture of lymphocytes showed active replication of HHV-6 in 79 of 113 patients (70%; CI, 61% to 78%) and in 8 of 40 controls (20%; CI, 9% to 36%) (P less than 10(-8], a finding confirmed by assays using monoclonal antibodies specific for HHV-6 proteins and by polymerase chain reaction assays specific for HHV-6 DNA [18].
• These novel cell lines should be useful for studying the mechanisms of HHV-6-induced hematopoietic failure and HHV-6 latency and reactivation, as well as differentiation, of the myeloid cell lineage [19].
• We describe in this work that another human herpesvirus, HHV-7, which shares genomic homology with HHV-6, also causes up-regulation of NK cell cytotoxicity via IL-15 induction [20].
• As human herpesvirus-6 (HHV-6) was recently shown to infect cervical epithelial cells in vitro and activate transcription of HPV-transforming genes, human cervical dysplasia and cancers were analyzed for the presence of HHV-6 by multiple methods, including polymerase chain reaction, slot blot, Southern blot, and in situ hybridization [21].
• Cell lines containing and expressing the human herpesvirus 6A ts gene are protected from both H-ras and BPV-1 transformation [22].

Gene context of Herpesvirus 6, Human

• The human herpesvirus 6 (HHV-6) U51 gene defines a new family of betaherpesvirus-specific genes encoding multiple transmembrane glycoproteins with similarity to G protein-coupled receptors, in particular, human chemokine receptors [23].
• This has further implications for neuroinflammatory diseases such as multiple sclerosis, where both cells bearing CCR1/CCR5 plus their ligands, as well as HHV-6A, have been linked [24].
• Down-regulation of CXCR4 by human herpesvirus 6 (HHV-6) and HHV-7 [25].
• A highly selective CCR2 chemokine agonist encoded by human herpesvirus 6 [26].
• An intriguing feature of the RCMV genome is the presence of an ORF, r127, with similarity to the rep gene of parvoviruses as well as ORF U94 of human herpesvirus 6A (HHV-6A) and HHV-6B [27].

Analytical, diagnostic and therapeutic context of Herpesvirus 6, Human

• Purified immature DC (derived from adherent peripheral blood mononuclear cells in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4) could be infected with HHV-6, as determined by PCR analyses, intracellular monoclonal antibody staining, and presence of virus in culture supernatants [28].
• In dual immunofluorescence assays, the infected cells were detected by antibodies against the HHV-6 p41 nuclear antigen and glial fibrillary acidic protein, indicating that the infected cells are indeed astrocytes [29].
• Immunohistochemistry using an antibody raised against the HHV-6 rep gene product (REP) revealed that REP was mainly present in the nucleus of MT-4 cells within 24 h after infection with HHV-6B [30].
• The recombinant protein expressed from the entire HHV-6 MCP gene was detected only weakly in Western blot assays with normal HHV-6-positive human sera as a probe [31].
• Flow cytometry and Scatchard analysis of TNF receptors revealed an increase in the number of the p55 form of TNF receptors on JJHAN cells after HHV-6 inoculation [32].

References