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In this study, the role of cholesterol in the envelope of human herpesvirus 6 (HHV-6) was examined by using methyl-β-cyclodextrin (MβCD) depletion. When cholesterol was removed from HHV-6 virions with MβCD, infectivity was abolished, but it could be rescued by the addition of exogenous cholesterol. HHV-6 binding was affected slightly by MβCD treatment. In contrast, envelope cholesterol depletion markedly affected HHV-6 infectivity and HHV-6-induced cell fusion. These results suggest that the cholesterol present in the HHV-6 envelope plays a prominent role in the fusion process and is a key component in viral entry.
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