PABP-driven secondary condensed phase within RSV inclusion bodies activates viral mRNAs for ribosomal recruitment  

作　　者：Qiang Zhang Hanzhe Ye Cong Liu Haiwu Zhou Mingbin He Xiaodong Liang Yu Zhou Kun Wang Yali Qin Zhifei Li Mingzhou Chen 

机构地区：[1]State Key Laboratory of Virology and Modern Virology Research Center,College of Life Sciences,Wuhan University,Wuhan,430072,China [2]Taikang Center for Life and Medical Sciences,Wuhan University,Wuhan,430072,China [3]Hubei Jiangxia Laboratory,Wuhan,430200,China

出　　处：《Virologica Sinica》2024年第2期235-250,共16页中国病毒学（英文版）

基　　金：supported by the grants from National Key R&D Program of China(2021YFC2300702 and 2021YFC2300200);the Hubei Provincial Natural Science Foundation of China(2021CFB364);the National Natural Science Foundation of China(82130064,81825015,U22A20337 and 32000119);the Key Biosafety Science and Technology Program of Hubei Jiangxia Laboratory(JXBS001).

摘　　要：Inclusion bodies(IBs)of respiratory syncytial virus(RSV)are formed by liquid-liquid phase separation(LLPS)and contain internal structures termed“IB-associated granules”(IBAGs),where anti-termination factor M2-1 and viral mRNAs are concentrated.However,the mechanism of IBAG formation and the physiological function of IBAGs are unclear.Here,we found that the internal structures of RSV IBs are actual M2-1-free viral messenger ribonucleoprotein(mRNP)condensates formed by secondary LLPS.Mechanistically,the RSV nucleoprotein(N)and M2-1 interact with and recruit PABP to IBs,promoting PABP to bind viral mRNAs transcribed in IBs by RNArecognition motif and drive secondary phase separation.Furthermore,PABP-eIF4G1 interaction regulates viral mRNP condensate composition,thereby recruiting specific translation initiation factors(eIF4G1,eIF4E,eIF4A,eIF4B and eIF4H)into the secondary condensed phase to activate viral mRNAs for ribosomal recruitment.Our study proposes a novel LLPS-regulated translation mechanism during viral infection and a novel antiviral strategy via targeting on secondary condensed phase.

关 键 词：Respiratory syncytial virus(RSV) Inclusion bodies(IBs) Biomolecular condensates Liquid-liquid phase separation(LLPS) Secondary condensed phase mRNA activation 

分 类 号：R373[医药卫生—病原生物学]