Study on the induction mechanism of hydroa vacciniforme and hypersensitivity to mosquito bites in the Epstein-Barr virus-associated lymphoma

点击翻译按钮获取中文摘要

Recent studies suggest that NK cell lymphocytosis associated with Epstein-Ban virus (EBV) infection often shows severe hypersensitivity to mosquito bites (HMB) characterized by intense local skin reactions and systemic symptoms such high fever, lymphadenopathy, and hepatosplenomegaly. However, the induction mechanism of HMB is still unclear. We investigated 6 cases of HMB to elucidate the mechanism explaining the relation between HMB and EBV-positive NK cell lymphocytosis. Proliferation assay showed that CD4+ T cells, but not CD8+ T cells or NK cells, responded to the mosquito extracts, especially to salivary gland extracts of Aedes albopictus. We showed that coculturing of the patients' NK cells and CD4+ T cells activated by mosquito extracts could induce expression of EBV lytic-cycle proteins in the NK cells. Prick test with the salivary gland extracts from various species of mosquito showed that the extracts from Aedes albopictus induced the most intensive skin reaction. Furthermore, RT-PCR analysis demonstrated that expression of BZLF1 , a viral lytic-cycle transactivator, was detectable at the skin lesions induced by mosquito bites. EBV DNA copy number levels in the plasma were elevated in systemic HMB symptoms compared to normal condition. These results suggest that CD4+ T cells are important for the primary skin reaction to mosquito bite and might play a key role in reactivation of latent EBV infection in NK cells. This viral reactivation contributed to the pathogenesis of the infectious mononucleosis-like systemic symptoms of HMB in the patients.