Identification of novel viral interleukin-10 isoforms of human cytomegalovirus AD169

Lin, Yi-Ling; Chang, Pei Ching; Wang, Yixiang; Li, Mengtao

doi:10.1016/j.virusres.2007.09.011

Cited by 32 publications

(48 citation statements)

References 41 publications

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“…14 Transcripts predicted to encode LAcmvIL-10 have also been detected during productive infection of human foreskin fibroblasts (HFs), 39 as have several additional viral IL-10 variants. 40 The detection of LAcmvIL-10 transcription during latent infection raised the possibility that LAcmvIL-10 may encode similar immunosuppressive properties to cmvIL-10. However, analysis of cells treated with recombinant LAcmvIL-10 protein demonstrated that its immunosuppressive properties are more restricted than those of cmvIL-10 as the only function reported to date has been the ability to down-regulate MHC class II on myeloid cells.…”

Section: Introductionmentioning

confidence: 99%

The role of the human cytomegalovirus UL111A gene in down-regulating CD4+ T-cell recognition of latently infected cells: implications for virus elimination during latency

Cheung

Gottlieb

Plachter

et al. 2009

Blood

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The capacity of human cytomegalovirus (HCMV) to establish and maintain a latent infection from which it can later reactivate ensures its widespread distribution in the population, but the mechanisms enabling maintenance of latency in the face of a robust immune system are poorly understood. We examined the role of the HCMV UL111A gene, which encodes homologs of the immunosuppressive cytokine interleukin-10 in the context of latent infection of myeloid progenitor cells. A UL111A deletion virus was able to establish, maintain, and reactivate from experimental latency in a manner comparable with parental virus, but major histocompatibility complex class II levels increased significantly on the surfaces of cells infected with the deletion virus. Importantly, there was an increase in both allogeneic and autologous peripheral blood mononuclear cells and CD4 ؉ Tcell responses to UL111A deletion virusinfected myeloid progenitors, indicating that loss of the capacity to express IntroductionHuman cytomegalovirus (HCMV) is a species-specific ␤-herpesvirus that infects a majority of the world's population. 1 During primary productive infection, both innate and adaptive immune responses are activated, and replicating virus is eventually cleared from the host. However, the virus is able to evade complete immune clearance by establishing and maintaining a life-long latent infection in hematopoietic cells, specifically those of the myeloid lineage. [2][3][4][5][6][7] During latency, detectable infectious virus production ceases, the viral genome is maintained as an extrachromosomal plasmid 8 at a low viral genome copy number, 7 and only a subset of viral genes remain transcriptionally active. [9][10][11][12][13][14] Reactivation from latency results in reinitiation of the full replicative cycle, with production of new infectious virus.Reactivation of HCMV from latency during states of reduced immune surveillance has profound implications for the management of patients with hematologic and immune deficiency disorders. In these clinical contexts, HCMV reactivation can lead to tissue infection causing major morbidity and mortality. As a result, the presence of HCMV seropositivity and thus of latent virus in donors or recipients of unrelated stem cell transplantations is an adverse prognostic feature despite major advances in HCMV monitoring and management. 15,16 Reactivation of HCMV is also of importance in seropositive patients with nontransplantation cellular immunodeficiencies, such as those resulting from human immunodeficiency virus infection, 17 or in seropositive patients with iatrogenically induced immunodeficiency, such as that resulting from treatment with the anti-CD52 antibody Campath. 18,19 There is no known therapy for the elimination of virus that persists during latency. Instead, where necessary, medical treatment has concentrated on the preemptive treatment or the prophylaxis of viral reactivation. Even here, no single strategy prevents reactivation while universally avoiding unnecessary therapy. There is an urge...

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Section: Introductionmentioning

confidence: 99%

The role of the human cytomegalovirus UL111A gene in down-regulating CD4+ T-cell recognition of latently infected cells: implications for virus elimination during latency

Cheung

Gottlieb

Plachter

et al. 2009

Blood

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“…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). The vast majority of characterization of functions has come from studies using recombinant viral IL-10 proteins, although some have also assessed function during productive infection with viruses with deficient viral IL-10 proteins.…”

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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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“…Additional studies have shown that cmvIL-10 can inhibit NF-B signaling in monocytes (Nachtwey and Spencer, 2008). Like human IL-10, the cmvIL-10 protein forms a dimer, and evidence suggests that cmvIL-10 can form heterodimers with human IL-10 that actually enhance Stat3 phosphorylation (Lin et al, 2008). receptor.…”

Section: Cell Signalingmentioning

confidence: 99%

Trojan Horses and Fake Immunity Idols: Molecular Mimicry of Host Immune Mediators by Human Cytomegalovirus

Spencer¹

2012

Herpesviridae - A Look Into This Unique Family of Viruses

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Identification of novel viral interleukin-10 isoforms of human cytomegalovirus AD169

Cited by 32 publications

References 41 publications

The role of the human cytomegalovirus UL111A gene in down-regulating CD4+ T-cell recognition of latently infected cells: implications for virus elimination during latency

The role of the human cytomegalovirus UL111A gene in down-regulating CD4+ T-cell recognition of latently infected cells: implications for virus elimination during latency

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

Trojan Horses and Fake Immunity Idols: Molecular Mimicry of Host Immune Mediators by Human Cytomegalovirus

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