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2'5' oligo(A) polymerase activity in serum of mice infected with EMC virus or treated with interferon
Abstract:
Interferon-treated cells show an increase in two double-stranded RNA (dsRNA)-dependent enzymatic activities involving an oligoadenylate polymerase and a protein kinase (ref. 1 and refs therein). The polymerase converts ATP into a series of oligonucleotides characterized by 2'5'-phosphodiester bonds, designated 2'5'-oligo(A) or 2-5A (ref. 1). These oligonucleotides activate an endoribonuclease that degrades RNA in extracts of control and interferon-treated cells. These observations have been made in tissue culture cells and no informatin is yet available on these enzymatic activities in animals with elevated interferon levels. We report here on 2-5A synthesis in tissue homogenates and serum of mice infected with encephalomyocarditis virus (EMCV); this virus induces interferon synthesis when injected intraperitoneally into mice. Significant synthesis of 2-5A was detected in extracts of spleen and lungs, but also, surprisingly, in the serum of these mice. Subsequent experiments showed synthesis of 2-5A in serum of mice treated with the interferon inducer poly(I) x poly(C) (ref. 3) or with mouse fibroblast interferon.
Insights
Interferon treatment activates enzymes that produce 2'5'-oligo(A) (2-5A). This study detects 2-5A synthesis in mouse tissues and serum after viral infection or interferon induction.
Area of Science:
- Biochemistry
- Immunology
- Molecular Biology
Background:
- Interferon treatment in cells increases dsRNA-dependent enzymatic activity.
- Oligoadenylate polymerase synthesizes 2'5'-oligo(A) (2-5A) from ATP.
- 2-5A activates an endoribonuclease that degrades RNA.
Purpose of the Study:
- To investigate 2-5A synthesis in animal models with elevated interferon levels.
- To determine if 2-5A synthesis occurs in vivo in response to viral infection.
Main Methods:
- Mice were infected with encephalomyocarditis virus (EMCV) or treated with interferon inducers.
- Tissue homogenates and serum were analyzed for 2-5A synthesis.
- Enzymatic activities were measured in spleen, lungs, and serum.
Main Results:
- Significant 2-5A synthesis was detected in spleen and lung homogenates of EMCV-infected mice.
- Surprisingly, 2-5A synthesis was also observed in the serum of infected mice.
- 2-5A synthesis was confirmed in the serum of mice treated with poly(I) x poly(C) or mouse fibroblast interferon.
Conclusions:
- 2-5A synthesis occurs in vivo in mice during viral infection and interferon induction.
- The presence of 2-5A in serum suggests systemic involvement of this pathway.
- These findings extend the understanding of interferon-inducible enzyme activity to animal models.
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