The effect of prostaglandins on the replication of adenovirus wild types and temperature-sensitive mutants.
Replication and transformation by adenoviruses involve their interaction with several cellular regulatory mechanisms. Alterations in the phosphorylation of both cellular and viral polypeptides by secondary messenger cAMP and cGMP dependent protein kinases (PK) determining outcome of viral effects may be influenced by external physiological stimuli, among them by prostaglandins (PG). HEp-2 cells infected with representative serotypes of human adenovirus (Ad) groups and two temperature sensitive (ts) mutants were treated prior to and late postinfection at permissive (32 degrees C) and restrictive (39 degrees C) temperatures by different PGs. PGF2 alpha augmented replication of both oncogenic Ad-12 and latent Ad-1, Ad-5 serotypes as well as Ad-5 mutants at 32 degrees C and that of mutant ts18 (defective in pVI phosphorylation) but not that of ts19 (defective in pX phosphorylation) at 39 degrees C. PGE2 was shown to be inhibitory, but the replication of nononcogenic Ad-8 was not affected by PGs. PGI2 slightly enhanced all types, while indomethacin, inhibitor of endogenous PG synthesis with double unsaturated bonds moderately inhibited replication of all serotypes, except that of Ad-12. It is concluded that augmenting effects by PGF2 alpha during viral entry, cytoplasmic transport and late phase, but not in the early phase of adenovirus replication cycle, are due to enhancement of the non-specific cellular mechanisms, which support mitosis in the uninfected cells. Their activities are controlled by the late viral replication machinery, which process had been programmed in the early interaction of viral and cellular regulatory factors.
Ongrádi
J
J
Institute of Microbiology, Semmelweis University Medical School, Budapest, Hungary.
Telekes
A
A
Farkas
J
J
Nász
I
I
Bendinelli
M
M
D000260:Adenoviruses, Human / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D009154:Mutation; D011453:Prostaglandins / Q000494:pharmacology*; D013696:Temperature; D014779:Virus Replication / Q000187:drug effects
D011453:Prostaglandins; D015237:Dinoprost; D011464:Epoprostenol; D000242:Cyclic AMP; D006152:Cyclic GMP; D015232:Dinoprostone; D007213:Indomethacin