Detection of Epstein-Barr virus DNA in saliva of HIV-1-infected individuals with oral hairy leukoplakia
Authors: Farisyi, Muhammad Al; Sufiawati, Irna
We present three cases of oral hairy leukoplakia (OHL) in whom the diagnosis was established by EBV DNA detection in whole saliva. Three HIV-infected patients came to the Oral Medicine Clinic with similar chief complaints of asymptomatic white lesions on the tongue. All patients were diagnosed with suspected OHL and oral thrush also in the first patient. A multiplex PCR DNA microarray was performed to detect EBV DNA in saliva collected by spitting method. All saliva samples showed positive results for EBV DNA, and the definitive diagnosis of OHL was made. Resolution of lesions was found at 1- to 2-month follow-up after treatment with application of acyclovir 5% cream 5 times daily. Additionally, anti-fungal treatment was given to the first patient and anti-retroviral treatment to the first and second patients. EBV is mostly transmitted by asymptomatic shedding into saliva. Therefore, the detection of salivary EBV DNA is useful in establishing a definitive diagnosis of OHL allowing more effective treatment for both HIV-infected patients receiving ART and treatment-naive patients at any CD4 + count.
IL-21 Stimulates the expression and activation of cell cycle regulators and promotes cell proliferation in EBV-positive diffuse large B cell lymphoma
Authors: Wang, Yuxuan; Wang, Chengcheng; Cai, Xiyunyi; Mou, Chang; Cui, Xueting; Zhang, Yingying; Ge, Feng; Dong, Hao; Hao, Yuanyuan; Cai, Lei; Wu, Shuting; Feng, Chenjie; Chen, Jiamin; Li, Jianyong; Xu, Wei; Fan, Lei; Xie, Weijia; Tong, Yue; Gu, Harvest Feng; Wu, Liang
The clinical features of EBV-positive diffuse large B cell lymphoma (DLBCL) indicate a poorer prognosis than EBV-negative DLBCL. Currently, there is no efficacious drug for EBV-positive DLBCL. The cytokine interleukin-21 (IL-21) has been reported to be pro-apoptotic in DLBCL cell lines and is being explored as a new therapeutic strategy for this type of lymphomas. However, our previous studies showed that IL-21 stimulation of EBV-positive DLBCL cell lines leads to increased proliferation. Here, analysis of a rare clinical sample of EBV-positive DLBCL, in combination with a NOD/SCID mouse xenograft model, confirmed the effect of IL-21 on the proliferation of EBV-positive DLBCL cells. Using RNA-sequencing, we identified the pattern of differentially-expressed genes following IL-21 treatment and verified the expression of key genes at the protein level using western blotting. We found that IL-21 upregulates expression of the host MYC and AP-1 (composed of related Jun and Fos family proteins) and STAT3 phosphorylation, as well as expression of the viral LMP-1 protein. These proteins are known to promote the G1/S phase transition to accelerate cell cycle progression. Furthermore, in NOD/SCID mouse xenograft model experiments, we found that IL-21 treatment increases glucose uptake and angiogenesis in EBV-positive DLBCL tumours. Although more samples are needed to validate these observations, our study reconfirms the adverse effects of IL-21 on EBV-positive DLBCL, which has implications for the drug development of DLBCL.