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bioRxiv · 10.64898/2026.10.26.761857

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

Verma, H.·Mukhopadhyay, S.·Lokeswara, B. S.·Das, R.·Kumar, A.·Balasubramanian, S.·Kondapi, A.
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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.

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Verma, H., Mukhopadhyay, S., Lokeswara, B. S., Das, R., Kumar, A., Balasubramanian, S., Kondapi, A.. 2026-10-28. Topoisomerase IIβ Kinase: A protein processed from HIV-1 envelope by cysteine proteases. https://doi.org/10.64898/2026.10.26.761857

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