[Age-dependent changes in "intracellular immunity" to virus infections].
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.
Schröder
H C
HC
Institut für Physiologische Chemie, Universität, Mainz, Germany.
Kelve
M
M
Pfeifer
K
K
Flögel-Mrsic
M
M
Müller
W E
WE
D015088:2',5'-Oligoadenylate Synthetase / Q000502:physiology; D000227:Adenine Nucleotides / Q000378:metabolism*; D000375:Aging / Q000276:immunology*; D000818:Animals; D000831:Animals, Newborn; D000998:Antiviral Agents / Q000502:physiology*; D016922:Cellular Senescence / Q000276:immunology*; D004722:Endoribonucleases / Q000502:physiology; D005260:Female; D008297:Male; D009843:Oligoribonucleotides / Q000378:metabolism*; D051381:Rats; D011914:Rats, Inbred BN; D014018:Tissue Distribution
D000227:Adenine Nucleotides; D000998:Antiviral Agents; D009843:Oligoribonucleotides; C023505:2',5'-oligoadenylate; D015088:2',5'-Oligoadenylate Synthetase; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease
Alternsabhängige Veränderungen der "intrazellulären Immunität" gegen Virusinfektionen.