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Updated: Jul 10, 2025

Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity
Published on: June 14, 2024
HIV-1 replication requires optimal activation of the unfolded protein response
Anjali Tripathi1, Kruthika Iyer1, Debashis Mitra1
1National Centre for Cell Science, Pune, India.
Abstract:
Several human diseases including viral infections activate the unfolded protein response (UPR) due to abnormal accumulation of unfolded/misfolded proteins. However, UPR modulation and its functional relevance in HIV-1 infection lack comprehensive elucidation. This study reveals that HIV-1 activates IRE1, PERK, and ATF6 signaling pathways of UPR. The knockdown of PERK and ATF6 reduces HIV-1 long terminal repeat (LTR)-driven gene expression, whereas the endoplasmic reticulum (ER) chaperone HSPA5 prevents proteasomal degradation of HIV-1 p24 through its chaperone activity. Interestingly, overstimulation of UPR by a chemical inducer leads to anti-HIV activity through an enhanced type-1 interferon response. Also, treatment with a chemical ER stress inhibitor reduces HIV-1 replication. These findings suggest that an optimal UPR activation is crucial for effective viral replication, as either overstimulating UPR or inhibiting ER stress leads to viral suppression.
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