* The Epstein-Barr Virus Lytic Protein BMLF1 Induces Upregulation of GRP78 Expression through ATF6 Activation.
- The unfolded protein response (UPR) is an intracellular signaling pathway essential for alleviating the endoplasmic reticulum (ER) stress. To support the productive infection, many viruses are known to use different strategies to manipulate the UPR signaling network. However, it remains largely unclear whether the UPR signaling pathways are modulated in the lytic cycle of Epstein-Barr virus (EBV), a widely distributed human pathogen. Herein, we show that the expression of GRP78, a central UPR regulator, is up-regulated during the EBV lytic cycle. Our data further revealed that knockdown of GRP78 in EBV-infected cell lines did not substantially affect lytic gene expression; however, GRP78 knockdown in these cells markedly reduced the production of virus particles. Importantly, we identified that the early lytic protein BMLF1 is the key regulator critically contributing to the activation of the grp78 gene promoter. Mechanistically, we found that BMLF1 can trigger the proteolytic cleavage and activation of the UPR senor ATF6, which then transcriptionally activates the grp78 promoter through the ER stress response elements. Our findings therefore provide evidence for the connection between the EBV lytic cycle and the UPR, and implicate that the BMLF1-mediated ATF6 activation may play critical roles in EBV lytic replication.
=>反応, 応答, 返答, 返報, 反響, 答唱句
Overview of noun response
The noun response has 7 senses (first 5 from tagged texts)
1. (11) response -- (a result; "this situation developed in response to events in Africa")
2. (11) reaction, response -- (a bodily process occurring due to the effect of some antecedent
stimulus or agent; "a bad reaction to the medicine"; "his responses have slowed with age")
3. (6) answer, reply, response -- (a statement (either spoken or written) that is made to reply to a
question or request or criticism or accusation; "I waited several days for his answer"; "he wrote
replies to several of his critics")
4. (4) reception, response -- (the manner in which something is greeted; "she did not expect the
cold reception she received from her superiors")
5. (1) response -- (a phrase recited or sung by the congregation following a versicle by the priest
or minister)
6. reply, response -- (the speech act of continuing a conversational exchange; "he growled his
reply")
7. response -- (the manner in which an electrical or mechanical device responds to an input signal
or a range of input signals)
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