Topoisomerase IIβ Kinase: A protein processed from HIV-1 envelope by cysteine proteases

Topoisomerase IIβ kinase (TopoIIβK) is produced within 15–30 minutes after HIV-1 infection, is conserved across subtypes A–D, and shows subtype-specific formation kinetics.

• Why it matters: Early HIV-1 infection depends on conserved host/viral processing events, but the origin and timing of TopoIIβK formation were unclear across major viral subtypes.
• What they did: The study measured TopoIIβK appearance post-infection, tested conservation across HIV-1 subtypes A, B, C, and D, mapped its gp120 source using anti-gp120 antibodies, and assessed endolysosomal localization and cysteine-protease dependence.
• The result: TopoIIβK co-localizes with endolysosomes shortly after entry, and cysteine protease inhibition with E64d or Z-FY-CHO abrogates its production in HIV-1-infected and envelope-transfected cells, supporting gp120 processing within endolysosomes.