Anatomical mapping of human herpesvirus reservoirs of infection

Chen, Tiansheng; Hudnall, S. David

doi:10.1038/modpathol.3800584

Cited by 96 publications

(86 citation statements)

References 53 publications

(59 reference statements)

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“…However, the mechanisms leading to the lymphangiogenic response during virus-induced inflammation have not yet been defined. In this regard, although early reports have shown the presence of HCMV antigens and DNA in lymphoid tissues (Boriskin et al, 1999;Chen & Hudnall, 2006), the importance LECs as a target of HCMV infection has remained unaddressed due to the lack of suitable in vitro experimental systems.…”

Section: Introductionmentioning

confidence: 99%

Human cytomegalovirus productively infects lymphatic endothelial cells and induces a secretome that promotes angiogenesis and lymphangiogenesis through interleukin-6 and granulocyte-macrophage colony-stimulating factor

Fiorentini

Luganini

Dell’Oste

et al. 2010

Journal of General Virology

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Endothelial cells (ECs) are a site of human cytomegalovirus (HCMV) productive replication, haematogenous dissemination and persistence, and are assumed to play a critical role in the development of HCMV-associated vascular diseases. Although early reports have shown the presence of HCMV antigens and DNA in lymphoid tissues, the ability of HCMV to infect lymphatic ECs (LECs) has remained unaddressed due to the lack of a suitable in vitro system. This study provided evidence that a clinical isolate of HCMV (retaining its natural endotheliotropism) was able to productively infect purified lymph node-derived LECs and that it dysregulated the expression of several LEC genes involved in the inflammatory response to viral infection. Qualitative and quantitative analysis of virus-free supernatants from HCMV-infected LEC cultures revealed virus-induced secretion of several cytokines, chemokines and growth factors, many of which are involved in the regulation of EC physiological properties. Indeed, functional assays demonstrated that the secretome produced by HCMV-infected LECs stimulated angiogenesis in both LECs and blood ECs, and that neutralization of either interleukin (IL)-6 or granulocytemacrophage colony-stimulating factor (GM-CSF) in the secretome caused the loss of its angiogenic properties. The involvement of IL-6 and GM-CSF in the HCMV-mediated angiogenesis was further supported by the finding that the recombinant cytokines reproduced the angiogenic effects of the HCMV secretome. These findings suggest that HCMV induces haemangiogenesis and lymphangiogenesis through an indirect mechanism that relies on the stimulation of IL-6 and GM-CSF secretion from infected cells.

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Section: Introductionmentioning

confidence: 99%

Human cytomegalovirus productively infects lymphatic endothelial cells and induces a secretome that promotes angiogenesis and lymphangiogenesis through interleukin-6 and granulocyte-macrophage colony-stimulating factor

Fiorentini

Luganini

Dell’Oste

et al. 2010

Journal of General Virology

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“…However, several reports have provided evidence that cumulatively suggest that the primary site of hematopoiesis, the bone marrow, may serve as a site for latent gammaherpesvirus infection. Both EBV (8) and KSHV (10) have been detected in the bone marrow of AIDS patients. KSHV has also been detected in the bone marrow of transplant recipients (22).…”

mentioning

confidence: 99%

Immature and Transitional B Cells Are Latency Reservoirs for a Gammaherpesvirus

Coleman

Nealy

Tibbetts

2010

J Virol

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The human gammaherpesviruses Epstein-Barr virus (EBV)and Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8 ) are ubiquitous human pathogens that are associated with the development of numerous types of malignancies, including B cell lymphomas. Murine gammaherpesvirus 68 (MHV68) is genetically related to EBV and KSHV and causes lymphoma and lymphoproliferative disease in mice, providing a useful small-animal model for mechanistic in vivo studies of the virus-host relationship. Both the human and murine viruses subvert the antiviral immune response to establish lifelong latent infections in mature B cells. However, it is not clearly understood how these viruses gain access to specific mature B cell subsets or whether latent infection of these subsets is actively maintained over time. One intriguing possibility is that gammaherpesviruses gain entry to the circulating mature B cell compartment via infection of B cell progenitors. Mature B cells arise via a highly regulated, multistep developmental process that results in the daily generation of thousands of new cells. Thus, any developing B cell subsets could provide a potential access point for recurrent entry of the virus into the long-lived mature B cell reservoir.

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“…Human herpesviruses (HHVs) are ubiquitous with widespread tissue tropism and have been found in the thyroid, which can be a reservoir of latent HHVs (9). HHVs have been isolated from 72.22% of thyroid tissue blocks of patients with Graves' disease (GD) and Hashimoto's thyroiditis (10).…”

Section: Introductionmentioning

confidence: 99%

Herpesvirus type 7 infection may play an important role in individuals with a genetic profile of susceptibility to Graves' disease

Leite

Bufalo²,

Santos³

et al. 2010

European Journal of Endocrinology

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Objective: An inherited profile of genes related to the response to aggressive environmental factors such as viruses and chemicals may be related to an increased susceptibility to Graves' disease (GD). Design and methods: This prospective case-control study was designed to examine the relationship between human herpesviruses (HHV) infection, determined by circulating DNA; tumour protein p53 (TP53) apoptotic ability; and detoxification system genes, and GD. We studied 280 confirmed GD patients paired to 284 controls with respect to environmental exposure. Exclusion criteria included medications that could interfere with thyroid function evaluation and a recent history of viral and bacterial infections. Results: A stepwise regression analysis adjusted for age, gender, and ethnicity established the inheritance of glutathione S-transferase pi 1 (GSTP1) (odds ratio (OR)Z3.423; 95% confidence interval (CI)Z2.120-5.527; P!0.001) and cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) variants (ORZ1.649; 95% CIZ1.012-2.686; PZ0.0445) as significant risk factors for the disease. HHV-7 infection was much more common in GD patients (64.64%) than in controls (38.73%; c 2 , P!0.0001), and it increased the risk for GD more than three times (ORZ3.133; 95% CIZ1.959-5.011; P!0.0001). The inheritance of less efficient Pro/Pro TP53 gene variants significantly increased the risk of GD development (ORZ5.196;; P!0.0001) and also favored HHV-7 infection (ORZ2.835; 95% CIZ1.100-7.310; PZ0.0275). In addition, 72TP53 variants augmented the risk of GD relapse (ORZ1.860; 95% CIZ1.015-3.410; PZ0.0446). Conclusions: We suggest that an inherited genetic profile involving TP53 may favor HHV-7 infection and maintenance, which, in turn, may initiate and perpetuate GD autoimmune process.

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Anatomical mapping of human herpesvirus reservoirs of infection

Cited by 96 publications

References 53 publications

Human cytomegalovirus productively infects lymphatic endothelial cells and induces a secretome that promotes angiogenesis and lymphangiogenesis through interleukin-6 and granulocyte-macrophage colony-stimulating factor

Human cytomegalovirus productively infects lymphatic endothelial cells and induces a secretome that promotes angiogenesis and lymphangiogenesis through interleukin-6 and granulocyte-macrophage colony-stimulating factor

Immature and Transitional B Cells Are Latency Reservoirs for a Gammaherpesvirus

Herpesvirus type 7 infection may play an important role in individuals with a genetic profile of susceptibility to Graves' disease

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