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

Topoisomerase IIβ (TopoIIβ) is activated by TopoIIβ kinase (TopoIIβK) during HIV-1 infection. This study demonstrates that TopoIIβK is produced within 15-30 minutes post-infection and is conserved across the major HIV-1 subtypes (A, B, C, and D), although its formation kinetics vary among subtypes. Immunological mapping using specific anti-gp120 antibodies suggests that TopoIIβK is derived from the N-terminal region of gp120. Notably, TopoIIβK co-localizes with endolysosomes shortly after viral entry. Inhibition of cysteine proteases using E64d and Z-FY-CHO abrogates TopoIIβK production in both HIV-1-infected and envelope-transfected cells. These findings suggest that TopoIIβK is a conserved polypeptide product of gp120 processing within endolysosomes during the early stages of HIV-1 infection, highlighting a potentially conserved mechanism that regulates early viral infection across major HIV-1 subtypes.