[Age-dependent changes in "intracellular immunity" to virus infections].

Abstract

A study of the antiviral 2',5'-oligoadenylate (2-5A) system in different tissues of rats of different age (newborn: 1-day old; young adult: 2-3 month old; middle-aged adult: 12-month old; and old: 32-33-month old) revealed that the activities of the 2-5A metabolic enzymes alter during aging and development. We demonstrate that soluble 2-5A synthase (2-5OAS) activity strongly increases after birth, reaching maximal levels in young adult and middle-aged adult animals, and then significantly decreases with age. In contrast, the activity of 2',3'-exoribonuclease which inactivates 2-5A increases by three-fold with age. The decrease in 2-5OAS activity and increase in 2-5A nuclease activity were found to result in a decrease in the cellular 2-5A content with age. The 2-5A-dependent ribonuclease (RNase L), which degrades viral RNA, also changes age-dependently. The amount and activity of this enzyme were determined in cross-linking experiments, in nitrocellulose binding assays; and in the ribosomal RNA cleavage assay. The livers of old rats display a 5-6-fold decrease in RNase L activity compared to the adult animal groups, while the amount of the enzyme does not change significantly during aging, with the exception of a drop by 30% in the nuclear matrix fraction. We conclude that the antiviral activity of the 2-5A system is impaired in old cells with the consequence that virus production cannot be efficiently suppressed.