ABSTRACT
Enterovirus A71 (EV-A71 or EV-71) is an RNA virus that causes hand, foot and mouse disease in children. The N6-methyladenosine (m6A) of RNA is a common RNA modification involved in various biological events. METTL3 is an m6A methyltransferase that regulates EV-71 replication. EV-71 infection induces autophagy, which also promotes EV-71 replication. In this study, we explored the role of METTL3 in EV-71 infection-induced autophagy. We constructed lentivirus expressing METTL3-specific shRNA and knocked down the endogenous METTL3 in mouse Schwann cells. We infected normal Schwann cells and METTL3 knockdown Schwann cells and compared the viral titer, expression of autophagy-related proteins and apoptosis-related protein. Transduction of lentivirus expressing METTL3 shRNA significantly decreased the endogenous METTL3. Knocking down METTL3 decreased the viral titer of EV-71 after infection. Knocking down METTL3 prevented EV-71-induced cell death and suppressed EV-71-induced expression of Bax while rescuing Bcl-2 expression after EV-71 infection. Knocking down METTL3 inhibited EV-71-induced expression of Atg5, Atg7 and LC3 II. Knocking down METTL3 inhibited EV-71-induced apoptosis and autophagy. In summary, our study describes the relationship of METTL3 and autophagy during EV-71 infection.
Subject(s)
Apoptosis , Autophagy , Enterovirus A, Human/genetics , Enterovirus A, Human/metabolism , Methyltransferases/genetics , Methyltransferases/metabolism , Schwann Cells/metabolism , Animals , Cell Death , Enterovirus Infections/metabolism , Enterovirus Infections/virology , Gene Knockdown Techniques/methods , Humans , Mice , RNA, Small Interfering/metabolism , Schwann Cells/virology , Virus ReplicationABSTRACT
BACKGROUND: Cow's milk protein allergy (CMPA) is commonly seen in children. There have been no reports of the true prevalence of CMPA in Chinese infants. The aim of this population-based study is to determine the prevalence, clinical characteristics, and outcome of CMPA in Chinese infants. METHODS: We carried out a prospective survey in 7 participating hospitals throughout southern China. We included infants ≤12 months of age during the survey. For those suspected of CMPA, oral food challenge with cow's milk protein (CMP) was performed. A follow-up telephone interview was conducted at 12 months after the diagnosis to assess the clinical outcome of CMPA. RESULTS: A total of 9910 questionnaire surveys were distributed and 7364 (74.3%) were returned. The eligible survey number of surveys was 6768 (91.9%). A total of 182 infants was confirmed with CMPA, including 13 with anaphylactic reactions, 28 with clinical symptoms and serum immunoglobulin E (sIgE) >3.5 IU/mL, and 141 with positive CMP challenge test. The prevalence of CMPA was 2.69%. Infants with confirmed CMPA had significantly stronger family history of either 1 or both parents with food allergy, higher Cesarean section rate, and lower rate of breastfeeding, compared with those without CMPA. At 12-month telephone follow-up of 176 CMPA infants, 136 infants (77.3%) had become tolerant to CMP. CONCLUSIONS: The prevalence of CMPA was 2.69%. CMPA infants had a strong family history of food allergy and atopy. Both Cesarean delivery and formula feeding were risk factors for CMPA. At 12-month follow-up, the majority of CMPA infants had become tolerant to CMP.
