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Researchers conducted a systematic screen of 37 kinetochore-associated proteins to identify host factors required for Kaposi's sarcoma-associated herpesvirus (KSHV) to maintain its genome during latent infection. The study identified two previously unknown proteins, CENP-B and LIC2, that are essential for viral episome stability and replication. Loss of these proteins significantly impaired the virus's ability to persist in host cells by disrupting its attachment to chromosomes during cell division.
Why it matters
This work reveals new host-virus interactions that KSHV exploits to establish lifelong infection and expands our understanding of how viral genomes hijack cellular machinery. The identified proteins represent potential therapeutic targets for treating KSHV-associated cancers like Kaposi's sarcoma, offering new avenues for drug development.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
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.