A homolog of interleukin-10 is encoded by the poxvirus orf virus

Fleming, Stephen B.; McCaughan, Catherine A.; Andrews, Arna E.; Nash, Andrew D.; Mercer, Andrew A.

doi:10.1128/jvi.71.6.4857-4861.1997

Cited by 186 publications

(59 citation statements)

References 29 publications

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“…Viral inhibition of antigen presentation, suppression, or neutralization of antiviral cytokines and induction of selective immune suppression are pathways that are used by some viruses in their quest for survival. [76][77][78][79] Thus far, however, there is no evidence that these processes are operative during HCV infection, or any of the other persistent hepatotropic viruses, for that matter. Interestingly, HCV core protein has been shown to interact with several cellular factors including the tumor necrosis factor receptor-related lymphotoxin-␤ receptor (LT-␤R).…”

Section: Mechanisms Potentially Involved In Viral Persistencementioning

confidence: 99%

Pathogenesis of chronic hepatitis C: Immunological features of hepatic injury and viral persistence

1999

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The immune response to viral antigens is thought to be responsible for viral clearance and disease pathogenesis during hepatitis C virus (HCV) infection. In chronically infected patients, the T-cell response to the HCV is polyclonal and multispecific, although it is not as strong as the response in acutely infected patients who display a more vigorous T-cell response. Importantly, viral clearance in acutely infected patients is associated with a strong CD4 ؉ helper T-cell response. Thus, the dominant cause of viral persistence during HCV infection may be the development of a weak antiviral immune response to the viral antigens, with corresponding inability to eradicate infected cells. The most striking feature of hepatitis C is its tendency toward chronicity. The hepatitis C virus (HCV) contains a positive-stranded RNA genome of about 10 kilobases, which contains a single uninterrupted open reading frame that encodes a protein of 3010-3011 amino acids. 1,2 The virus is classified as a Flavivirus. HCV infects an estimated 400 million people, corresponding to more than 3% of the world population. 3 Numerous partial and complete nucleotide sequences have been derived from geographically widespread HCV isolates. The data indicate substantial sequence diversity within, and especially between, each geographic area. The European and American isolates appear to be more closely related to each other than to the Japanese isolates. Based on a polymerase chain reaction-based algorithm, a classification system has been proposed by Okamoto 4 and revised by Simmonds. 5 Different viral sequences (quasispecies) have been isolated from the same patient upon sequential sampling, and multiple isolates have been reported in a single sample. 6 The degree of similarity between isolates at the amino acid level varies from genome region to region. The nucleocapsid protein (core) has the highest sequence homology among all isolates sequenced to date. In contrast, the E1 and E2/NS1 regions present the highest degree of sequence variability among different isolates; in particular, the N terminal portion of E2/NS1 contains a hypervariable region of 30 amino acids, which shows extensive variation between virtually all known isolates. 7 The major extracellular loop of CD81, a cell-surface protein widely expressed on B and T lymphocytes and other cells including hepatocytes, has been shown to bind E2. 8 The recent success of isolating a cDNA clone capable of generating infectious RNA transcripts may be an important step toward the development of a tissue culture system. 9,10 The only animal model, the chimpanzee, mirrors several features of human HCV infection. Most importantly, the frequency of persistent infection is high in both species, and virus replication occurs despite evidence of cellular and humoral immune responses. 11,12 A key difference is that necroinflammatory lesions in chronically infected chimpanzees are almost always mild, whereas in humans, the disease spectrum is very wide, ranging from mild to severe hepatitis and end-sta...

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Section: Mechanisms Potentially Involved In Viral Persistencementioning

confidence: 99%

Pathogenesis of chronic hepatitis C: Immunological features of hepatic injury and viral persistence

1999

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“…Indeed, recombinant BCRF1 protein was shown to mimic the activity of IL-10 (Hsu et al, 1990), namely inhibition of cytokine synthesis by activated human peripheral blood mononuclear cells and by a mouse Th1 cell clone (Vieira et al, 1991). Since then, a number of other viruses have also been shown to encode a homologue of the Il10 gene (Fleming et al, 1997;Kotenko et al, 2000;Jayawardane et al, 2008). Soon after the discovery of IL-10, its pleiotropic action was unveiled initially in the mouse, not only as a cytokine synthesis inhibitory factor, but additionally as a mast cell (Thompson-Snipes et al, 1991) and thymocyte (MacNeil et al, 1990) growth factor, and as an activator of B cells (Go et al, 1990;Rousset et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Biology and therapeutic potential of interleukin-10

Saraiva

Vieira

O’Garra

2019

Journal of Experimental Medicine

585

423

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The cytokine IL-10 is a key anti-inflammatory mediator ensuring protection of a host from over-exuberant responses to pathogens and microbiota, while playing important roles in other settings as sterile wound healing, autoimmunity, cancer, and homeostasis. Here we discuss our current understanding of the regulation of IL-10 production and of the molecular pathways associated with IL-10 responses. In addition to IL-10’s classic inhibitory effects on myeloid cells, we also describe the nonclassic roles attributed to this pleiotropic cytokine, including how IL-10 regulates basic processes of neural and adipose cells and how it promotes CD8 T cell activation, as well as epithelial repair. We further discuss its therapeutic potential in the context of different diseases and the outstanding questions that may help develop an effective application of IL-10 in diverse clinical settings.

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“…29 The second is coded by orf virus belonging to the parapox family. 30 Very recently a third viral version of IL-10 was discovered, coded by cytomegalovirus, which has minimal homology with the cellular IL-10. 31 No gene coding for IL-10 has been described in the HSV genome thus far, and it seems probable that the cellular IL-10 is up-regulated, rather than a viral gene.…”

Section: Discussionmentioning

confidence: 99%

Infection of murine keratinocytes with herpes simplex virus type 1 induces the expression of interleukin‐10, but not interleukin‐1α or tumour necrosis factor‐α

et al. 2001

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SUMMARYHerpes simplex virus (HSV) is known to possess several mechanisms whereby it can evade the normal host immune defences. In this study the expression of the immunosuppressive cytokine, interleukin (IL)-10, was monitored following infection of a murine keratinocyte cell line (PAM-212) and compared with the expression of two proin¯ammatory cytokines: IL-1a and tumour necrosis factor (TNF)-a. The PAM-212 cells were infected at a multiplicity of 0 . 5 with a clinical isolate of HSV type 1, and the mRNA of the three cytokines was assessed by semiquantitative reverse transcription±polymerase chain reaction (RT±PCR) over the following 24 hr. By 12 hr postinfection the amount of IL-10 mRNA had increased signi®cantly to ®ve-fold greater than that found in uninfected cells (P<0 . 01), and this elevated level was maintained until at least 24 hr postinfection. In contrast, IL-1a and TNF-a mRNAs were not signi®cantly up-regulated by the HSV infection. Immunostaining with an IL-10 monoclonal antibody (mAb) revealed that cytoplasmic IL-10 protein had increased by 6 ±12 hr postinfection. This quantity was further increased at 24 hr postinfection, when the viral cytopathic effect was apparent. Viral replication was necessary, but not suf®cient on its own, for IL-10 induction. Experiments with HSV mutants lacking functional transactivating factors suggested that the viral transactivating proteins ICP-0 and VP-16 may be necessary for HSV-induced IL-10 expression. Thus, the up-regulation in the expression of IL-10 mRNA and protein induced by HSV early in the infection of keratinocytes represents a speci®c response and may be part of the viral strategy to avoid local immune defence mechanisms in the skin.

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A homolog of interleukin-10 is encoded by the poxvirus orf virus

Cited by 186 publications

References 29 publications

Pathogenesis of chronic hepatitis C: Immunological features of hepatic injury and viral persistence

Pathogenesis of chronic hepatitis C: Immunological features of hepatic injury and viral persistence

Biology and therapeutic potential of interleukin-10

Infection of murine keratinocytes with herpes simplex virus type 1 induces the expression of interleukin‐10, but not interleukin‐1α or tumour necrosis factor‐α

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