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.O ne almost never finds two different viruses in the same cell. SignificancePrimary effusion lymphoma (PEL) is a B cell lymphoma; the prognosis is poor, with a median survival around 6 months. PEL is always associated with the presence of Kaposi's sarcomaassociated herpesvirus and in most cases is coinfected with Epstein-Barr virus (EBV); however, the role of EBV in the pathogenesis of the tumor is still not clear. This study demonstrates the intricate interaction between the two herpesviruses, which exacerbate tumorigenesis by mutually reinforcing the persistence of each latent genome and by altering cell proliferation. It establishes curing EBV and inhibiting Epstein-Barr nuclear antigen 1 as a potential treatment for PEL.

This study was conducted to evaluate seasonal groundwater quality due to groundwater pumping and hydrochemical characteristics with groundwater level fluctuations in an agricultural area in Korea. Groundwater levels were observed for about one year using automatic monitoring sensors, and groundwater uses were estimated based on the monitoring data. Groundwater use in the area is closely related to irrigation for rice farming, and rising groundwater levels occur during the pumping, which may be caused by the irrigation water of rice paddies. Hydrochemical analysis results for two separate times (17 July and 1 October 2019) show that the dissolved components in groundwater decreased overall due to dilution, especially at wells in the alluvial aquifer and shallow depth. More than 50% of the samples were classified as CaHCO3 water type, and changes in water type occurred depending on the well location. Water quality changes were small at most wells, but changes at some wells were evident. In addition, the groundwater quality was confirmed to have the effect of saltwater supplied during the 2018 drought by comparison with seawater. According to principal component analysis (PCA), the water quality from July to October was confirmed to have changed due to dilution, and the effect was strong at shallow wells. In the study areas where rice paddy farming is active in summer, irrigation water may be one of the important factors changing the groundwater quality. These results provide a qualitative and quantitative basis for groundwater quality change in agricultural areas, particularly rice paddies areas, along with groundwater level and usage.

Kaposi's sarcoma-associated herpesvirus (KSHV) induces B cell hyperplasia and neoplasia, such as multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL). To explore KSHV-induced B cell reprogramming , we expressed the KSHV latency locus, inclusive of all viral microRNAs (miRNAs), in B cells of transgenic mice in the absence of the inhibitory FcγRIIB receptor. The BALB/c strain was chosen as this is the preferred model to study B cell differentiation. The mice developed hyperglobulinemia, plasmacytosis, and B lymphoid hyperplasia. This phenotype was ameliorated by everolimus, which is a rapamycin derivative used for the treatment of mantle cell lymphoma. KSHV latency mice exhibited hyperresponsiveness to the T-dependent (TD) antigen mimic anti-CD40 and increased incidence of pristane-induced inflammation. Lastly, the adaptive immunity against a secondary infection with Zika virus (ZIKV) was markedly enhanced. These phenotypes are consistent with KSHV lowering the activation threshold of latently infected B cells, which may be beneficial in areas of endemicity, where KSHV is acquired in childhood and infections are common. Kaposi's sarcoma-associated herpesvirus (KSHV) establishes latency in B cells and is stringently linked to primary effusion lymphoma (PEL) and the premalignant B cell hyperplasia multicentric Castleman's disease (MCD). To investigate potential genetic background effects, we expressed the KSHV miRNAs in BALB/c transgenic mice. BALB/c mice are the preferred strain for B cell hybridoma development because of their propensity to develop predictable B cell responses to antigen. The BALB/c latency mice exhibited a higher incidence of B cell hyperplasia as well as sustained hyperglobulinemia. The development of neutralizing antibodies against ZIKV was augmented in BALB/c latency mice. Hyperglobulinemia was dampened by everolimus, a derivative of rapamycin, suggesting a role for mTOR inhibitors in managing immune activation, which is hallmark of KSHV infection as well as HIV infection.

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cInterleukin 6 (IL-6) is considered a proliferation and survival factor for B cells. To assess the role of IL-6 in Kaposi sarcoma-associated herpesvirus (KSHV) latency, KSHV latency locus-transgenic mice (referred to as latency mice) lacking IL-6 were evaluated. IL-6 ؊/؊ latency mice had the same phenotypes as the latency mice, i.e., increased frequency of marginal zone B cells, hyperplasia, and hyperglobulinemia, indicating that the KSHV latency locus, which includes all viral microRNAs (miRNAs), can compensate for lack of IL-6 in premalignant B cell activation.

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