Rice yellow stunt virus activates polyamine biosynthesis to promote viral propagation in insect vectors by disrupting ornithine decarboxylase antienzyme function

摘要

Intracellular polyamines(putrescine,spermidine,and spermine)have emerged as important molecules for viral infection;however,how viruses activate polyamines biosynthesis to promote viral infection remains unclear.Ornithine decarboxylase 1(ODC1)and its antienzyme 1(OAZ1)are major regulators of polyamine biosynthesis in animal cells.Here,we report that rice yellow stunt virus(RYSV),a plant rhabdovirus,could activate putrescine biosynthesis in leafhoppers to promote viral propagation by inhibiting OAZ1 expression.We observed that the reduction of putrescine biosynthesis by treatment with difluormethylornithine(DFMO),a specific nontoxic inhibitor of ODC1,or with in vitro synthesized dsRNAs targeting ODC1 mRNA could inhibit viral infection.In contrast,the supplement of putrescine or the increase of putrescine biosynthesis by treatment with ds RNAs targeting OAZ1 mRNA could facilitate viral infection.We further determined that both RYSV matrix protein M and ODC1 directly bind to the ODC-binding domain at the C-terminus of OAZ1.Thus,viral propagation in leafhoppers would decrease the ability of OAZ1 to target and mediate the degradation of ODC1,which finally activates putrescine production to benefit viral propagation.This work reveals that polyamine-metabolizing enzymes are directly exploited by a vector-borne virus to increase polyamine production,thereby facilitating viral infection in insect vectors.