Human Cytomegalovirus Reactivation in Bone-Marrow-Derived Granulocyte/Monocyte Progenitor Cells and Mature Monocytes

Prösch, Susanna; Döcke, Wolf‐Dietrich; Reinke, Petra; Volk, Hans‐Dieter; Krüger, Detlev H.

doi:10.1159/000053965

Cited by 38 publications

(39 citation statements)

References 32 publications

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“…6A and B) or tumor necrosis factor alpha (TNF-␣) (Fig. 6B), two cytokines that correlate with HCMV reactivation episodes in vivo (11,44). We next analyzed infectious-virus production in the DC cocultures, and as an additional set of controls, we analyzed infectious virus production from MoDCs and the monocyte-and DCdepleted fraction (predominantly lymphocytes) from naturally latent donors.…”

Section: Dendritic Cells Directly Isolated From Peripheral Blood Are mentioning

confidence: 99%

“…However, carriage of the virus appears to be restricted only to certain cell types within the hematopoietic system, in particular, cells of the myeloid lineage such as monocytes, their circulating progenitors, and subsequent derivatives (9)(10)(11)(12)(13)(14). This carriage of viral genomes occurs in the absence of any significant viral lytic gene expression (reviewed in reference 15); hence, cells of the myeloid lineage represent an important site of latency and persistence in the host.…”

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Circulating Dendritic Cells Isolated from Healthy Seropositive Donors Are Sites of Human Cytomegalovirus Reactivation In Vivo

Reeves

2013

J Virol

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Primary infection with human cytomegalovirus (HCMV) is generally asymptomatic in healthy individuals and results in a lifelong infection of the host. In contrast, in immunosuppressed transplant recipients and late-stage AIDS patients, HCMV infection and reactivation can result in severe disease or death. In vivo, latency is established in bone marrow CD34؉ progenitor cells with reactivation linked with their differentiation to macrophages and dendritic cells (DCs). However, previous analyses have relied on ex vivo differentiation of myeloid progenitor cells to DCs in culture. Here, we now report on the isolation and analysis of circulating blood myeloid DCs, resulting from natural differentiation in vivo, from healthy HCMV-seropositive carriers. We show that these in vivo-differentiated circulating DCs are fully permissive for HCMV and exhibit a phenotype similar to that of monocyte-derived DCs routinely used for in vitro studies of HCMV. Importantly, we also show that these DCs from healthy HCMV-seropositive donors carry HCMV genomes and, significantly, are typically positive for viral immediate-early (IE) gene expression, in contrast to circulating monocytes, which carry genomes with an absence of IE expression. Finally, we show that HCMV reactivation from these circulating DCs is enhanced by inflammatory stimuli. Overall, these data argue that the differentiation in vivo of myeloid progenitors to circulating DCs promotes the reactivation of HCMV lytic gene expression in healthy individuals, thereby providing valuable confirmation of studies performed using in vitro generation of DCs from myeloid precursors to study HCMV reactivation.

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Section: Dendritic Cells Directly Isolated From Peripheral Blood Are mentioning

confidence: 99%

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confidence: 99%

Circulating Dendritic Cells Isolated from Healthy Seropositive Donors Are Sites of Human Cytomegalovirus Reactivation In Vivo

Reeves

2013

J Virol

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“…The host inflammatory response, triggered by whatever kind of stimuli, plays a key role in reactivating CMV and stimulating viral gene expression. In turn, viral gene products upregulate host production of a variety of proinflammatory mediators, including IL-6, IL-1, IFN and TNF-␣ as well as a variety of chemokines [123,[133][134][135][136] . It was hypothesized that the presence of inflammation, whether resulting from CMV infection or from other sources, would synergistically increase the association between CMV and frailty.…”

Section: Chronic Antigenic Exposure: the Role Of Human Cytomegalovirusmentioning

confidence: 99%

Immunosenescence and Immunogenetics of Human Longevity

Ostan

Bucci²,

Capri³

et al. 2008

Neuroimmunomodulation

162

100

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At present, individuals can live up to 80–120 years, a time much longer than that of our ancestors, as a consequence of the improvements in life conditions and medical care. Thus, the human immune system has to cope with a lifelong and evolutionarily unpredicted exposure to a variety of antigens, which are at the basis of profound age-related changes globally indicated as immunosenescence, a multifaceted phenomenon that increases morbidity and mortality due to infections and age-related pathologies. The major changes occurring during immunosenescence are the result of the accumulation of cellular, molecular defects and involutive phenomena (such as thymic involution) occurring concomitantly to a hyperstimulation of both innate and adaptive immunity (accumulation of expanded clones of memory and effector T cells, shrinkage of the T cell receptor repertoire, progressive activation of macrophages), and resulting in a low-grade, chronic state of inflammation defined as inflammaging. It is unknown whether inflammaging, which represents a risk factor for most age-related pathologies, is a cause or rather an effect of the aging process. In this complex scenario, the role of genetic background likely represents a fundamental variable to attain successful aging and longevity. Accordingly, centenarians seem to be equipped with gene variants that allow them to optimize the balance between pro- and anti-inflammatory molecules, and thus to minimize the effects of the lifelong exposure to environmental insults and stressors. The remarkable features of the genetics of aging and longevity are reviewed, stressing the unexpected and unusual results obtained regarding such a postreproductive type of genetics.

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“…An informed consensus supports the myeloid lineage as an important site of HCMV latency and carriage (Hahn et al, 1998;Mendelson et al, 1996;Sindre et al, 1996;TaylorWiedeman et al, 1991) and that terminal myeloid differentiation is concomitant with HCMV reactivation (Hahn et al, 1998;Prosch et al, 1999;Reeves et al, 2005a, b;Soderberg-Naucler et al, 1997;Taylor-Wiedeman et al, 1994). A recurrent theme in HCMV latency/reactivation, this differentiation-dependent permissiveness also applies to lytic infection (Hertel et al, 2003;Lathey & Spector, 1991;Riegler et al, 2000).…”

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confidence: 99%

Analysis of latent viral gene expression in natural and experimental latency models of human cytomegalovirus and its correlation with histone modifications at a latent promoter

Reeves

2009

Journal of General Virology

102

134

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Human Cytomegalovirus Reactivation in Bone-Marrow-Derived Granulocyte/Monocyte Progenitor Cells and Mature Monocytes

Cited by 38 publications

References 32 publications

Circulating Dendritic Cells Isolated from Healthy Seropositive Donors Are Sites of Human Cytomegalovirus Reactivation In Vivo

Circulating Dendritic Cells Isolated from Healthy Seropositive Donors Are Sites of Human Cytomegalovirus Reactivation In Vivo

Immunosenescence and Immunogenetics of Human Longevity

Analysis of latent viral gene expression in natural and experimental latency models of human cytomegalovirus and its correlation with histone modifications at a latent promoter

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