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Epstein-Barr virus enhances genome maintenance of Kaposi sarcoma-associated herpesvirus.

ABSTRACT: Primary effusion lymphoma (PEL) is a B cell lymphoma that is always associated with Kaposi's sarcoma-associated herpesvirus (KSHV) and in many cases also with Epstein-Barr virus (EBV); however, the requirement for EBV coinfection is not clear. Here, we demonstrate that adding exogenous EBV to KSHV⁺ single-positive PEL leads to increased KSHV genome maintenance and KSHV latency-associated nuclear antigen (LANA) expression. To show that EBV was necessary for naturally coinfected PEL, we nucleofected KSHV⁺/EBV⁺ PEL cell lines with an EBV-specific CRISPR/Cas9 plasmid to delete EBV and observed a dramatic decrease in cell viability, KSHV genome copy number, and LANA expression. This phenotype was reversed by expressing Epstein-Barr nuclear antigen 1 (EBNA-1) in trans, even though EBNA-1 and LANA do not colocalize in infected cells. This work reveals that EBV EBNA-1 plays an essential role in the pathogenesis of PEL by increasing KSHV viral load and LANA expression.

SUBMITTER: Bigi R

PROVIDER: S-EPMC6275488 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Epstein-Barr virus enhances genome maintenance of Kaposi sarcoma-associated herpesvirus.

Bigi Rachele R Landis Justin T JT An Hyowon H Caro-Vegas Carolina C Raab-Traub Nancy N Dittmer Dirk P DP

Proceedings of the National Academy of Sciences of the United States of America 20181114 48

Primary effusion lymphoma (PEL) is a B cell lymphoma that is always associated with Kaposi's sarcoma-associated herpesvirus (KSHV) and in many cases also with Epstein-Barr virus (EBV); however, the requirement for EBV coinfection is not clear. Here, we demonstrate that adding exogenous EBV to KSHV<sup>+</sup> single-positive PEL leads to increased KSHV genome maintenance and KSHV latency-associated nuclear antigen (LANA) expression. To show that EBV was necessary for naturally coinfected PEL, we ...[more]

PMID: 30429324

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Epstein-Barr virus enhances genome maintenance of Kaposi sarcoma-associated herpesvirus.

Publications

Epstein-Barr virus enhances genome maintenance of Kaposi sarcoma-associated herpesvirus.

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