Azathioprine inhibits vaccinia virus replication in both BSC-40 and RAG cell lines acting on different stages of virus cycle.
In the present study we demonstrate that azathioprine (AZA) inhibits vaccinia virus (VV) replication in both BSC-40 and RAG cell lines, acting on different stages of virus cycle. In BSC-40 cells, early protein synthesis was not significantly affected, but late gene expression was severely impaired. In RAG cells all stages of gene expression were completed during synchronous infection in the presence of the drug. The onset of DNA replication was not affected in RAG cells, but a severe inhibition was observed in BSC-40 cells. Electron microscopic analysis of VV-infected RAG cells treated with AZA revealed brick-shaped particles presenting abnormal definition of the internal structure. Purified virions from AZA-treated RAG cells presented several modifications of the protein content, a lesser amount of DNA, and a lower PFU:particle ratio. Our results suggest that in VV-infected RAG cells AZA interfered with virus morphogenesis, whereas in BSC-40 cells the replicative cycle was inhibited at the DNA replication stage.
Laboratório de Biologia Molecular de Vi;rus, Instituto de Biofi;sica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-590, Rio de Janeiro, Brazil.
Clarissa R A
CR
Damaso
Marcus F
MF
Oliveira
Susana M
SM
Massarani
Nissin
N
Moussatché
D000230:Adenocarcinoma; D000818:Animals; D001379:Azathioprine / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D004261:DNA Replication / Q000187:drug effects; D005814:Genes, Viral / Q000187:drug effects*; D007668:Kidney; D007680:Kidney Neoplasms; D051379:Mice; D016615:Telomere / Q000187:drug effects; D013997:Time Factors; D014616:Vaccinia virus / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D014764:Viral Proteins / Q000096:biosynthesis / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
D014764:Viral Proteins; D001379:Azathioprine