
The endoplasmic reticulum (ER) chaperone BiP/GRP78 is upregulated during the lytic cycle of the oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV) and acts as a pro-viral factor, promoting viral replication and the survival/proliferation of KSHV-infected cells.


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The Endoplasmic Reticulum (ER)-resident HSP70 chaperone BiP (HSPA5) plays a crucial role in maintaining and restoring protein folding homeostasis in the ER. BiP’s function is often dysregulated in cancer and virus-infected cells, conferring pro-oncogenic and pro-viral advantages. We explored BiP’s functions during infection by the Kaposi’s sarcoma-associated herpesvirus (KSHV), an oncogenic gamma-herpesvirus associated with cancers of immunocompromised patients. Our findings reveal that BiP protein levels are upregulated in infected epithelial cells during the lytic phase of KSHV infection. This upregulation occurs independently of the unfolded protein response (UPR), a major signaling pathway that regulates BiP availability. Genetic and pharmacological inhibition of BiP halts KSHV viral replication and reduces the proliferation and survival of KSHV-infected cells. Notably, inhibition of BiP limits the spread of other alpha- and beta-herpesviruses and poxviruses with minimal toxicity for normal cells. Our work suggests that BiP is a potential target for developing broad-spectrum antiviral therapies against double-stranded DNA viruses and a promising candidate for therapeutic intervention in KSHV-related malignancies.

### Competing Interest Statement

The authors have declared no competing interest.

BiP/GRP78 is a pro-viral factor for diverse dsDNA viruses that promotes the survival and proliferation of cells upon KSHV infection

the-endoplasmic-reticulum-chaperone-bip-grp78-is-a-pro-viral-factor-that-promotes-survival-and-proliferation-of-cells-infected-with-the-oncogenic-kaposi-s-sarcoma-associated-herpesvirus


The Endoplasmic Reticulum Chaperone BiP/GRP78 is a Pro-Viral Factor that Promotes Survival and Proliferation of Cells Infected with the Oncogenic Kaposi's Sarcoma-Associated Herpesvirus
