Molecular chaperone Hsp90 is important for vaccinia virus growth in cells.
Molecular chaperones assist protein folding, and some chaperones are induced by heat, nutrient depletion, or pathogen invasion. This study investigates the role played by Hsp90 in the life cycle of vaccinia virus. The titer of vaccinia intracellular mature virions (IMV) was reduced by 2 orders of magnitude in RK13 cells treated with geldanamycin (GA), which blocks the ATPase activity of Hsp90. GA does not affect expression from the viral early promoter, but treatment with GA delays DNA replication and intermediate gene transcription and reduces expression from the viral late promoter. Vaccinia virus infection does not induce Hsp90 expression; however, intracellular distribution of Hsp90 is altered in virus-infected cells. Hsp90 is restricted to the cytoplasm of mock-infected cells; in contrast, Hsp90 is transiently associated with virosomes in virus-infected cells although it is not incorporated into IMV. In addition, Hsp90 interacts with viral core protein 4a, the mature form of the A10L gene product, in virus-infected cells. In conclusion, these results suggest that a cellular chaperone protein, Hsp90, is important for vaccinia virus growth in cultured cells and that viral core protein 4a associates with Hsp90-containing complexes in the infected cells.
Hung
Jan-Jong
JJ
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, Republic of China.
Chung
Che-Sheng
CS
Chang
Wen
W
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D016227:Benzoquinones; D002478:Cells, Cultured; D004279:DNA, Viral / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005814:Genes, Viral; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D047029:Lactams, Macrocyclic; D011809:Quinones / Q000494:pharmacology; D013347:Subcellular Fractions; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014616:Vaccinia virus / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D014758:Viral Core Proteins / Q000378:metabolism; D022701:Virosomes
D016227:Benzoquinones; D004279:DNA, Viral; D004791:Enzyme Inhibitors; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D011809:Quinones; D014758:Viral Core Proteins; D022701:Virosomes; D000251:Adenosine Triphosphatases; C001277:geldanamycin