Wortmannin delays transfer of human rhinovirus serotype 2 to late endocytic compartments.
Human rhinovirus 2 (HRV2) is internalized by members of the low-density lipoprotein receptor family into early endosomes (pH 6.2-6.0) where it dissociates from its receptors. After transfer into late endosomes, the virus undergoes a conformational change and RNA uncoating solely induced by pH < 5.6. Finally, virus capsids are degraded in lysosomes. To investigate the role of phosphatidylinositol 3-kinases (PI3K) in the HRV2 entry route, we used the inhibitor wortmannin. Although virus internalization was not altered by wortmannin, virus accumulated in enlarged early endosomes. Furthermore, the drug delayed HRV2 degradation and viral protein synthesis. Consequently, wortmannin-sensitive PI3K are involved in HRV2 transport from early to late compartments. However, wortmannin had no effect on the titer of infectious virus produced. Our data therefore suggest that virus retained in early endosomes for prolonged time periods can undergo the conformational change that otherwise occurs at pH < or = 5.6 in late endosomes.
Brabec
Marianne
M
Department of Pathophysiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Blaas
Dieter
D
Fuchs
Renate
R
D000730:Androstadienes / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D011992:Endosomes / Q000187:drug effects / Q000821:virology*; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012229:Rhinovirus / Q000472:pathogenicity* / Q000502:physiology; D014168:Transferrin / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects; D000077191:Wortmannin
D000730:Androstadienes; D000081082:Phosphoinositide-3 Kinase Inhibitors; D014168:Transferrin; D014764:Viral Proteins; D000077191:Wortmannin