Kinetochore Proteins CENPB and LIC2 are critical for Episome Persistence and Replication of Kaposis's Sarcoma-Associated Herpesvirus
- 1University of Pennsylvania
Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV) establishes lifelong latency by maintaining its genome as circular episomes tethered to host chromatin and faithfully segregated during mitosis. This process is primarily mediated by the latency-associated nuclear antigen (LANA), which interacts with host chromosome-associated factors to ensure viral genome persistence. Several kinetochore proteins, including CENP-F, Bub1, BubR1, Aurora B, Survivin, and NuMA, have been implicated in this process, yet the broader contribution of kinetochore components remains poorly defined. We performed a systematic shRNA-based screen of the 37 host genes encoding kinetochore-associated proteins to evaluate their role in KSHV episome maintenance. We validated involvement of previously reported factors and identified Centromere Protein B (CENP-B) and Light Intermediate Chain 2 of the dynein complex (LIC2) as novel kinetochore-associated proteins critical for KSHV episome persistence. Loss of these proteins significantly reduced episome stability, highlighting previously unrecognized host-virus interactions at the chromosome segregation machinery. These findings identify critical host factors that expand the repertoire of kinetochore proteins co-opted by KSHV for episome maintenance and provide new mechanistic insights into how viral episomes exploit host chromosome segregation pathways for long-term persistence. Our work underscores kinetochore proteins as a broader class of host dependency factors in gamma-herpesvirus biology and suggests potential therapeutic targets for KSHV-associated malignancies.
Related
- Persistence of viral full-length genomic RNA and replication-associated RNA transcripts and proteins in sheep tissues following acute Crimean-Congo hemorrhagic fever virus infection
- Kaposi's sarcoma-associated herpesvirus forms and maintains R-loops at origins of lytic replication
- Mutations in VP1 and 3A proteins improve binding and replication of rhinovirus C15 in HeLa-E8 cells
- Amygdala Persistence in Aging: Replication and Extension of Puccetti et al. (2021)
- SAMSN1 restricts Japanese encephalitis virus replication by recruiting TRIM21 to degrade viral proteins and activate the interferon pathway
BibTeX
@misc{singh2026kinetochore,
title = {{Kinetochore Proteins CENPB and LIC2 are critical for Episome Persistence and Replication of Kaposis's Sarcoma-Associated Herpesvirus}},
author = {R. K. Singh and S. Zhang and D. Bose and N. Ma and R. Vangala and K. Chunduru and E. S. Robertson},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.28.762626},
url = {https://www.biorxiv.org/content/10.64898/2026.10.28.762626v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Kinetochore Proteins CENPB and LIC2 are critical for Episome Persistence and Replication of Kaposis's Sarcoma-Associated Herpesvirus
AU - R. K. Singh
AU - S. Zhang
AU - D. Bose
AU - N. Ma
AU - R. Vangala
AU - K. Chunduru
AU - E. S. Robertson
PY - 2026
DA - 2026/10/28
PB - bioRxiv
DO - 10.64898/2026.10.28.762626
UR - https://www.biorxiv.org/content/10.64898/2026.10.28.762626v1
AB - Kaposi's sarcoma-associated herpesvirus (KSHV) establishes lifelong latency by maintaining its genome as circular episomes tethered to host chromatin and faithfully segregated during mitosis. This process is primarily mediated by the latency-associated nuclear antigen (LANA), which interacts with host chromosome-associated factors to ensure viral genome persistence. Several kinetochore proteins, including CENP-F, Bub1, BubR1, Aurora B, Survivin, and NuMA, have been implicated in this process, yet the broader contribution of kinetochore components remains poorly defined. We performed a systematic shRNA-based screen of the 37 host genes encoding kinetochore-associated proteins to evaluate their role in KSHV episome maintenance. We validated involvement of previously reported factors and identified Centromere Protein B (CENP-B) and Light Intermediate Chain 2 of the dynein complex (LIC2) as novel kinetochore-associated proteins critical for KSHV episome persistence. Loss of these proteins significantly reduced episome stability, highlighting previously unrecognized host-virus interactions at the chromosome segregation machinery. These findings identify critical host factors that expand the repertoire of kinetochore proteins co-opted by KSHV for episome maintenance and provide new mechanistic insights into how viral episomes exploit host chromosome segregation pathways for long-term persistence. Our work underscores kinetochore proteins as a broader class of host dependency factors in gamma-herpesvirus biology and suggests potential therapeutic targets for KSHV-associated malignancies.
ER -