Epstein-Barr virus (EBV) infects more than 90% of the world’s adult population and accounts for a significant cancer burden of epithelial and B cell origins. Glycoprotein B (gB) is the primary fusogen essential for EBV entry into host cells. Here, we isolated two EBV gB-specific neutralizing antibodies, 3A3 and 3A5; both effectively neutralized the dual-tropic EBV infection of B and epithelial cells. In humanized mice, both antibodies showed effective protection from EBV-induced lymphoproliferative disorders. Cryoelectron microscopy analyses identified that 3A3 and 3A5 bind to nonoverlapping sites on domains D-II and D-IV, respectively. Structure-based mutagenesis revealed that 3A3 and 3A5 inhibit membrane fusion through different mechanisms involving the interference with gB-cell interaction and gB activation. Importantly, the 3A3 and 3A5 epitopes are major targets of protective gB-specific neutralizing antibodies elicited by natural EBV infection in humans, providing potential targets for antiviral therapies and vaccines.
Introduction: Hematoporphyrin monomethyl ether-photodynamic therapy (HMME-PDT) has been showing promising results in the treatment of port-wine stains (PWSs). We evaluated the clinical efficacy and treatment response of HMME-PDT in adult Chinese patients with PWSs. Methods: A single-center retrospective study recruited adult PWS patients with negative HMME skin test results from December 2017 to May 2020. Patients received an intravenous injection of 5 mg/kg HMME and the lesions were exposed to 532 nm LED green light with an irradiation power density of 85-95 mW/cm 2 for 20-25 min. Digital photographs were taken before and after two therapy sessions and observed by three blinded dermatologists for clinical response. Results: A total of 72 patients aged between 18 and 55 years were recruited. There were 65 patients of the flat purple type, 5 of the hypertrophic type, and 2 of the nodular thickening type. Of the 65 patients, 7 showed excellent efficacy (10.77%), 13 patients indicated good efficacy (20.00%), 47 patients showed fair efficacy (64.62%), while 3 cases displayed no improvement (4.62%). All five patients of the purple and hypertrophic type showed fair efficacy (100%), and no improvement was observed in patients of the nodular thickening type (100%). Pain, pruritus, and a burning sensation were observed during treatment. Edema was noted on the treated areas post-treatment. No other obvious systemic adverse reactions were observed. Conclusion: HMME-PDT is an effective and safe treatment for adult patients with purple PWSs. Multiple HMME-PDT treatments can improve the response and cure rate.
Nasopharyngeal carcinoma (NPC) and Epstein–Barr virus (EBV)–associated gastric carcinoma (EBVaGC) are two major EBV-associated epithelial malignancies, both of which are characterized by the infiltration of a large number of lymphocytes, including natural killer (NK) cells. Although NK cells can prevent the development of EBV-associated epithelial malignancies, EBV-infected tumor cells often develop resistance to surveillance by NK cells. Elucidating the interactions between NK cells and EBV-infected tumor cells will facilitate the development of more effective NK-mediated therapies for treating EBV-associated malignancies. Here we investigated the cytotoxic function of NK cells in EBV-associated epithelial malignancies and discovered that EBV infection-induced upregulation of F3 expression correlates with NK-cell dysfunction in NPC and EBVaGC. The subsequent inhibitory effect of F3-mediated platelet aggregation on NK-cell function was verified in vitro and in vivo. Mechanistically, EBV latent membrane protein 2A (LMP2A) mediated upregulation of F3 through the PI3K/AKT signaling pathway. In an NPC xenograft mouse model, inhibition of F3 restored the antitumor function of NK cells and showed therapeutic efficacy when administered with NK-cell transfer. On the basis of these findings, EBV infection induces F3-mediated platelet aggregation that inhibits the antitumor function of NK cells, providing a rationale for developing and combining NK-cell–based therapies with F3 inhibitors to treat EBV-associated epithelial malignancies. Significance: This study reveals a mechanism by which EBV-associated epithelial malignancies escape NK-cell–mediated immune surveillance, providing a new target for improving NK-cell immunotherapy.
Introduction: Although pulsed dye laser (PDL) remains the gold standard for the treatment of port-wine stains (PWS), hematoporphyrin monomethyl ether photodynamic therapy (HMME-PDT) is another treatment modality that has been shown to be effective in the treatment of PWS. This study aimed to observe the clinical efficacy and therapeutic response of HMME-PDT in the treatment of pediatric Chinese patients with PWS and to analyze the association between the efficacy of therapy and the dermoscopic features of PWS. Methods: Pediatric patients with PWS and negative HMME skin test were enrolled between Xin-yu Zhang and Najwa Al-Odaini share first authorship.
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