Differential outcomes of human cytomegalovirus infection in primitive hematopoietic cell subpopulations

Goodrum, Felicia; Jordan, Craig T.; Terhune, Scott S.; High, Kevin P.; Shenk, Thomas

doi:10.1182/blood-2003-12-4344

Cited by 132 publications

(170 citation statements)

References 44 publications

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“…During latency, characterized by a lack of production of infectious virus, viral genomes are carried in cells where viral lytic transcription is suppressed, and only a subset of viral genes are expressed (1)(2)(3)(4)(5). It is now clear that reactivation of virus from these latent pools is also a major cause of the HCMV-mediated disease observed in the immunocompromised/immunonaïve setting.…”

mentioning

confidence: 99%

Human cytomegalovirus latency alters the cellular secretome, inducing cluster of differentiation (CD)4⁺T-cell migration and suppression of effector function

Mason

Poole

Sissons

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

118

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After primary infection, human cytomegalovirus (HCMV) persists as a life-long latent infection, with host immunosuppression often resulting in clinical reactivation. During lytic infection, major changes in the expression of secreted cellular proteins (the secretome) occur that have profound effects on host–cell interactions, particularly at the level of the host immune response. In contrast, little is known about changes in the secretome that accompany latent infection, yet this is likely to be of major importance for the life-long carriage of this persistent human pathogen in the face of constant immunosurveillance. We have analyzed the secretome of cells carrying latent HCMV and have identified changes in several secreted cellular proteins known to be involved in regulation of the immune response and chemoattraction. Here, we show that a latency-associated increase in CC chemokine ligand (CCL)8 results in the recruitment of cluster of differentiation (CD)4 + T cells to supernatants from latently infected CD34 + cells but that these latent supernatants, also rich in immunosuppressive factors, inhibit cytokine secretion and cytotoxicity of HCMV-specific T-helper (Th)1 CD4 + T cells. These results identify a strategy by which sites of latent HCMV can firstly recruit CD4 + T cells and then inhibit their antiviral effector functions, thereby aiding the maintenance of latent infection in the face of the host immune response.

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mentioning

confidence: 99%

Human cytomegalovirus latency alters the cellular secretome, inducing cluster of differentiation (CD)4⁺T-cell migration and suppression of effector function

Mason

Poole

Sissons

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

118

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“…Following terminal cell differentiation of these cells into myeloid dendritic cells (DCs) and macrophages, latent virus has the ability to reactivate, resulting in the production of new, infectious virions and often severe disease in immunocompromised individuals (11,14,28,37,49,50,59,63). Only a subset of viral genes are transcriptionally active during latency (2,8,12,13,17,23,34,47), including HCMV UL111A, a gene that encodes homologs of the potent immunomodulatory cytokine human interleukin-10 (hIL-10). UL111A is transcriptionally active during both productive and latent phases of infection and encodes several viral IL-10 proteins (17,(24)(25)(26)46) which exert a diverse range of immunomodulatory functions, including inhibition of cytokine synthesis and major histocompatibility complex (MHC) expression by myeloid cells, stimulation of B cells, and suppression of DC maturation and cytotrophoblast function (5-7, 9, 16, 18, 36, 51, 52, 61).…”

mentioning

confidence: 99%

Viral Interleukin-10 Expressed by Human Cytomegalovirus during the Latent Phase of Infection Modulates Latently Infected Myeloid Cell Differentiation

Avdic

Cao

Cheung

et al. 2011

J Virol

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The human cytomegalovirus UL111A gene is expressed during latent and productive infections, and it codes for homologs of interleukin-10 (IL-10). We examined whether viral IL-10 expressed during latency altered differentiation of latently infected myeloid progenitors. In comparison to infection with parental virus or mock infection, latent infection with a virus in which the gene encoding viral IL-10 has been deleted upregulated cytokines associated with dendritic cell (DC) formation and increased the proportion of myeloid DCs. These data demonstrate that viral IL-10 restricts the ability of latently infected myeloid progenitors to differentiate into DCs and identifies an immunomodulatory role for viral IL-10 which may limit the host's ability to clear latent virus.

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“…К таким патогенам относятся бета герпесвирус HCMV [34], гаммагерпесвирус EBV [31], полиомавирус JCV [30]. HCMV устанавливает пожизненную латентность в основном в миелоидных клетках (моноцитах, ней-трофильных гранулоцитах, макрофагах, дендритных клетках) [39]. Кроме клеток микроваскулярного эндотелия, астроцитов, перицитов, нейронов, мик-роглии, HCMV также может проникать в нейрональ-ные стволовые клетки [34,40].…”

Section: Ukrainianunclassified

Viruses in human central nervous system — invasion, transmission, and latency: a literature review

Tsymbalyuk¹,

Vasileva²

2017

Ukr Neurosurg J

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Differential outcomes of human cytomegalovirus infection in primitive hematopoietic cell subpopulations

Cited by 132 publications

References 44 publications

Human cytomegalovirus latency alters the cellular secretome, inducing cluster of differentiation (CD)4⁺T-cell migration and suppression of effector function

Human cytomegalovirus latency alters the cellular secretome, inducing cluster of differentiation (CD)4⁺T-cell migration and suppression of effector function

Viral Interleukin-10 Expressed by Human Cytomegalovirus during the Latent Phase of Infection Modulates Latently Infected Myeloid Cell Differentiation

Viruses in human central nervous system — invasion, transmission, and latency: a literature review

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Differential outcomes of human cytomegalovirus infection in primitive hematopoietic cell subpopulations

Cited by 132 publications

References 44 publications

Human cytomegalovirus latency alters the cellular secretome, inducing cluster of differentiation (CD)4+T-cell migration and suppression of effector function

Human cytomegalovirus latency alters the cellular secretome, inducing cluster of differentiation (CD)4+T-cell migration and suppression of effector function

Viral Interleukin-10 Expressed by Human Cytomegalovirus during the Latent Phase of Infection Modulates Latently Infected Myeloid Cell Differentiation

Viruses in human central nervous system — invasion, transmission, and latency: a literature review

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Human cytomegalovirus latency alters the cellular secretome, inducing cluster of differentiation (CD)4⁺T-cell migration and suppression of effector function

Human cytomegalovirus latency alters the cellular secretome, inducing cluster of differentiation (CD)4⁺T-cell migration and suppression of effector function