Infection of natural killer cells by human herpesvirus 6

Lusso, Paolo; Malnati, Mauro S.; Garzino-Demo, Alfredo; Crowley, R. Webster; Long, Eric O.; Gallo, Robert C.

doi:10.1038/362458a0

Cited by 182 publications

(128 citation statements)

References 27 publications

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“…HHV-6, by using CD46 as a cellular receptor, 51 has tropism for CD4 T lymphocytes, and it also interacts with other cells of the immune system such as natural killer cells and CD8 T lymphocytes; such interaction with the immune system results in decreased interleukin-2 levels and enhanced susceptibility to apoptosis. 48,52,53 HHV-7 uses CD4 as the cellular receptor to infect T cells. 54 The role of virus-induced immunomodulation as the sole or primary predictor of increased opportunistic infections has, however, been confounded by the iatrogenic pharmacologic immunomodulation that is inherent during the posttransplantation period.…”

Section: Indirect Effectsmentioning

confidence: 99%

The impact of human herpesvirus-6 and -7 infection on the outcome of liver transplantation

Razonable

Payá

2002

Liver Transplantation

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Human herpesvirus (HHV)-6 and -7 are novel members of the ␤-herpesvirus family that maintain latency in the human host after primary infection. Reactivation from latency and/or increased degree of viral replication occurs during periods of immune dysfunction. The clinical effect of HHV-6 and HHV-7 reactivation in recipients of liver transplants is now being recognized. Clinical illnesses such as fever, rash, pneumonitis, encephalitis, hepatitis, and myelosuppression have been described in a number of anecdotal reports. Moreover, a growing body of evidence suggests that the more important effect of HHV-6 and HHV-7 reactivation on the outcomes of liver transplantation may be mediated indirectly by their interactions with the other ␤-herpesvirus-cytomegalovirus (CMV). Coinfection among these three ␤-herpesviruses in clinical syndromes that were classically ascribed to be solely caused by CMV has been shown and has raised substantial interest in the potential role of HHV-6 and HHV-7 as copathogens in the direct and indirect illnesses caused by CMV. This article reviews the current scientific data on the role and the magnitude of impact of HHV-6 and HHV-7 infection on the outcomes of liver transplantation. (Liver Transpl 2002;8:651-658.)

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Section: Indirect Effectsmentioning

confidence: 99%

The impact of human herpesvirus-6 and -7 infection on the outcome of liver transplantation

Razonable

Payá

2002

Liver Transplantation

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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: 99%

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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“…One particular aspect of HHV-6 pathogenesis is its ability to infect cell types of hematopoietic origin. HHV-6 can infect T cells (7), B cells (1), NK cells (8), megakaryocytes (9), and monocytes/macrophages (10,11). It is also suggested that HHV-6 can establish a latent infection in the monocyte/macrophage lineage (10).…”

mentioning

confidence: 99%

Activation of Monocyte Cyclooxygenase-2 Gene Expression by Human Herpesvirus 6

Janelle¹,

Gravel²,

Gosselin³

et al. 2002

Journal of Biological Chemistry

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Prostaglandin E 2 (PGE 2 ) is an arachidonic acid metabolite mainly produced by activated monocytes/macrophages (Mo/M) that display broad immunomodulatory activities. Several viruses capable of infecting Mo/M modulate PGE 2 synthesis in a way that favors the infection processes and the spread of virions. In the present work, we studied the effect of human herpesvirus 6 (HHV-6) infection of Mo/M on PGE 2 synthesis. Our results indicate that HHV-6 induces COX-2 gene expression and PGE 2 synthesis within a few hours of infection. 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. HHV-6 immediate-early protein 2 was identified as a modulator of COX-2 gene expression in Mo/M. Finally, addition of PGE 2 to HHV-6-infected peripheral blood mononuclear cells cultures was found to increase significantly viral replication. Overall, these results further contribute to the immunomodulatory properties of HHV-6 and highlight a potential role for eicosanoids in the replication process of this virus.

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Infection of natural killer cells by human herpesvirus 6

Cited by 182 publications

References 27 publications

The impact of human herpesvirus-6 and -7 infection on the outcome of liver transplantation

The impact of human herpesvirus-6 and -7 infection on the outcome of liver transplantation

Human herpesvirus-6-associated acute lymphadenitis in immunocompetent adults

Activation of Monocyte Cyclooxygenase-2 Gene Expression by Human Herpesvirus 6

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