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

Abstract

Topoisomerase II{beta} (TopoII{beta}) is activated by TopoII{beta} kinase (TopoII{beta}K) during HIV-1 infection. This study demonstrates that TopoII{beta}K 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 TopoII{beta}K is derived from the N-terminal region of gp120. Notably, TopoII{beta}K co-localizes with endolysosomes shortly after viral entry. Inhibition of cysteine proteases using E64d and Z-FY-CHO abrogates TopoII{beta}K production in both HIV-1-infected and envelope-transfected cells. These findings suggest that TopoII{beta}K 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.