Activation of Interferon-Inducible Genes in Mice by Poly rI:rC or Alloantigens

Gariglio, Marisa; Cinato, Elisa; Panico, Saverio; Cavallo, G; Landolfo, Santo

doi:10.1097/00002371-199102000-00004

Cited by 14 publications

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“…However, the levels of Oas1a mRNA were dramatically induced in response to poly(I-C) treatment in multiple organs (Fig. 3A), which is consistent with previous studies (15,18,51). Whereas Oas1a was upregulated in response to poly(I-C) in all of the tissues examined, Oas1d was essentially unchanged (Fig.…”

supporting

confidence: 92%

Mice Deficient in Oocyte-Specific Oligoadenylate Synthetase-Like Protein OAS1D Display Reduced Fertility

Yan

Ma²,

Stein

et al. 2005

Mol Cell Biol

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The double-stranded RNA (dsRNA)-induced interferon response is a defense mechanism against viral infection. Upon interferon activation by dsRNA, 2,5-oligoadenylate synthetase 1 (OAS1A) is induced; it binds dsRNA and converts ATP into 2,5-linked oligomers of adenosine (called 2-5A), which activate RNase L that in turn degrades viral and cellular RNAs. In a screen to identify oocyte-specific genes, we identified a novel murine cDNA encoding an ovary-specific 2,5-oligoadenylate synthetase-like protein, OAS1D, which displays 59% identity with OAS1A. OAS1D is predominantly cytoplasmic and is exclusively expressed in growing oocytes and early embryos. Like OAS1A, OAS1D binds the dsRNA mimetic poly(I-C), but unlike OAS1A, it lacks 2-5 adenosine linking activity. OAS1D interacts with OAS1A and inhibits the enzymatic activity of OAS1A. Mutant mice lacking OAS1D (Oas1d ؊/؊ ) display reduced fertility due to defects in ovarian follicle development, decreased efficiency of ovulation, and eggs that are fertilized arrest at the one-cell stage. These effects are exacerbated after activation of the interferon/OAS1A/RNase L pathway by poly(I-C). We propose that OAS1D suppresses the interferon/OAS/RNase L-mediated cellular destruction by interacting with OAS1A during oogenesis and early embryonic development.Interferons (IFN) play an important role in the host defense mechanism against viral infection (38). The 2Ј-5Ј-oligoadenylate synthetases (OASs) belong to a family of IFN-induced antiviral proteins that are highly induced by alpha/beta IFN and to a lesser extent by gamma IFN (57). OAS proteins are produced as latent enzymes, which must bind double-stranded RNA (dsRNA) to form an enzymatically active complex that catalyzes the synthesis of 2Ј-5Ј-oligoadenylates (2-5A) from ATP. The 2-5A products bind to latent endoribonuclease RNase L, leading to its dimerization, activation, and degradation of cellular and viral RNA (16,27,69). dsRNA produced in virus-infected cells by either viral replication or symmetric transcription of the viral genome allows OAS enzymes to sense and react to viral infection (10, 28, 44), the outcome being a global inhibition of protein synthesis that blocks viral proliferation (38).OAS family genes have been characterized extensively in humans, and orthologous genes are also reported in mouse, rat, pig, chicken, and marine sponges (38). In humans, the OAS family consists of four classes of genes: OAS1 (p40/p46, short form), OAS2 (p69/p71, middle form), OAS3 (p100, long form), and OASL (p59, or OAS-related protein). The three human OAS genes (OAS1 to -3) are located on chromosome segment 12q24.1 where they form a cluster within a 130-kb genomic region, representing the OAS locus (24). The gene encoding OASL has been mapped to 12q24.2 (23). The two isoforms of OAS1 (p40/p46) are identical in their first 346 amino acids but have different carboxy termini generated by alternative splicing (1). Similarly, differential splicing of the transcripts from the OAS2 gene generates the p69/p71 isoforms (33). The shor...

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supporting

confidence: 92%

Mice Deficient in Oocyte-Specific Oligoadenylate Synthetase-Like Protein OAS1D Display Reduced Fertility

Yan

Ma²,

Stein

et al. 2005

Mol Cell Biol

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“…The synthetic, dsRNA analog, poly rI:rC has been shown to increase circulating levels of IFNs responsible for the induction of 202 mRNA in vivo [26]. DBA/2 mice were therefore injected intraperitoneally with poly rI:rC and 24 h later analyzed for both p204 and D3 expression.…”

Section: Resultsmentioning

confidence: 99%

The murine homolog of the HIN 200 family, Ifi 204, is constitutively expressed in myeloid cells and selectively induced in the monocyte/macrophage lineage

Gariglio

Andrea²,

Lembo³

et al. 1998

Journal of Leukocyte Biology

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“…Considering the 1 h blood persistence of the sIFNyR, as well as its capacity to antagonize the antiviral activity of IFN-y on L929 mouse fibroblasts (IC50 = 15 nM) [12], we calculated that injections of 100 pg sIFN-yR three times a week should be sufficient to maintain a concentration in the blood which is able to neutralize 10 U/ml of IFN-y, a concentration typically detected in body fluids [16]. A second group received 5 x lo4 U IFNy three times per week, according to Jacob et al [2].…”

Section: Treatment Of Nzbnv Mice With Sifn-yr or Ifn-ymentioning

confidence: 99%

Experimental therapy of systemic lupus erythematosus: the treatment of NZB/W mice with mouse soluble interferon‐γ receptor inhibits the onset of glomerulonephritis

et al. 1995

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Female NZB/W F1 mice develop an autoimmune disease similar to human systemic lupus erythematosus (SLE), and ultimately die of glomerulonephritis. Starting at the age of 16 weeks NZB/W F1 mice were treated for a period of 19 weeks with soluble interferon-gamma receptor (sIFN-gamma R), anti-IFN-gamma monoclonal antibody (mAb) or IFN-gamma. All mice treated with sIFN-gamma R or anti-IFN-gamma mAb were alive 4 weeks after the treatment was discontinued, whereas 50% of mice died in the placebo groups and 78% of the mice died in the IFN-gamma-treated group. Histologically, there was severe membrano-proliferative glomerulonephritis in IFN-gamma- and placebo-treated mice, and minimal or no mesangioproliferative disease in mice receiving sIFN-gamma R or anti-IFN-gamma mAb. The renal mononuclear infiltrate (T lymphocytes and monocytes), expression of major histocompatibility complex class II antigen and glomerular immunoglobulin and complement deposition were reduced in those mice. These data suggest that an IFN-gamma inhibitor, such as the soluble IFN-gamma R, can be used for SLE therapy in the early stages of the disease.

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Activation of Interferon-Inducible Genes in Mice by Poly rI:rC or Alloantigens

Cited by 14 publications

References 0 publications

Mice Deficient in Oocyte-Specific Oligoadenylate Synthetase-Like Protein OAS1D Display Reduced Fertility

Mice Deficient in Oocyte-Specific Oligoadenylate Synthetase-Like Protein OAS1D Display Reduced Fertility

The murine homolog of the HIN 200 family, Ifi 204, is constitutively expressed in myeloid cells and selectively induced in the monocyte/macrophage lineage

Experimental therapy of systemic lupus erythematosus: the treatment of NZB/W mice with mouse soluble interferon‐γ receptor inhibits the onset of glomerulonephritis

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