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REVIEW article

Front. Cell. Infect. Microbiol.

Sec. Virus and Host

Molecular Chaperones at the Host–Virus Interface: Heat Shock Protein Roles in HIV-1 and Emerging Insights for HIV-2 and Dual Infection

Provisionally accepted
Sabastine Eugene ArthurSabastine Eugene Arthur1,2*Kirk KlogoKirk Klogo2Emmanuel Kobina MensahEmmanuel Kobina Mensah2Maame Ama Pentsiwa CudjoeMaame Ama Pentsiwa Cudjoe1Adomia Baaba MensahAdomia Baaba Mensah2Nyamekye Amoabeng AnkrahNyamekye Amoabeng Ankrah2Catherine Laaripuoh OmosuleCatherine Laaripuoh Omosule1,3Evelyn Yayra BonneyEvelyn Yayra Bonney2*George KyeiGeorge Kyei1,2,4,5*
  • 1University of Ghana Medical Centre LTD, Legon, Ghana
  • 2University of Ghana Noguchi Memorial Institute for Medical Research, Accra, Ghana
  • 3Department of Pathology and Immunology, Washington University In St. Louis., St. Louis, United States
  • 4Departments of Medicine, Washington University School of Medicine in St. Louis, St. Louis, United States
  • 5Washington University in St Louis Department of Molecular Microbiology, St. Louis, United States

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Heat shock proteins (HSPs) are essential molecular chaperones involved in protein folding, cellular stress responses, and homeostasis. Recent studies reveal their critical and dual roles in the human immunodeficiency virus (HIV) life cycle, both promoting and restricting viral replication, latency, and immune modulation. This review synthesizes current evidence on how key HSP families, HSP70, HSP90, and HSP40, interact with HIV proteins such as Tat, Rev, Nef, and Vpx, affecting viral transcription, protein trafficking, and latency. We also highlight Heat Shock Factor 1 (HSF1) as a direct regulator of the HIV-1 long terminal repeat (LTR), facilitating latency reversal via recruitment of transcriptional co-activators like p300 and P-TEFb. In HIV-2, distinct HSP-mediated mechanisms, such as HSP40-facilitated nuclear import of Vpx-associated pre-integration complexes, may contribute to its lower replication rates and deeper latency. The review further discusses the incorporation of HSPs into virions, their potential as therapeutic targets, including HSP90 inhibitors and HSF1 modulators, and identifies gaps in understanding HSP roles in HIV-2 and dual infections. We propose future research directions that could harness host stress-response machinery to address HIV persistence and latency.

Keywords: Heat shock proteins, HIV latency, HIV-1 and HIV-2, HSF1, Latency-ReversingAgents (LRAs)

Received: 24 Oct 2025; Accepted: 18 Nov 2025.

Copyright: © 2025 Arthur, Klogo, Mensah, Cudjoe, Mensah, Ankrah, Omosule, Bonney and Kyei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Sabastine Eugene Arthur, sarthur@ugmc.ug.edu.gh
Evelyn Yayra Bonney, ebonney@noguchi.ug.edu.gh
George Kyei, gkyei@noguchi.ug.edu.gh

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material