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 ...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.展开更多
This study aimed to analyze frequencies of flavor detection signals occurring in any of the three respiratory phases and either of the two masticatory phases. Flavors of three fruity (grape, orange, and strawberry) gu...This study aimed to analyze frequencies of flavor detection signals occurring in any of the three respiratory phases and either of the two masticatory phases. Flavors of three fruity (grape, orange, and strawberry) gummy candies in the mouth were detected after chewing in 24 young healthy participants. The results revealed that: 1) more detection signals occurred in the expiratory phase than in the inspiratory or pausing phases and 2) more detection signals occurred in the jaw-closing phase than in the jaw-opening phase. Statistical analysis showed that the difference between the frequencies among the three respiratory phases was significant (P < 0.001) but not between the two masticatory phases. Further analysis showed that the frequencies occurring within individual respiratory phases were not significantly biased. The present results suggest that flavor detection during chewing depends more on the expiratory phase rather than the inspiratory and pausing phases, whereas detection is dependent to a lesser extent on either of the masticatory phases.展开更多
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)+1 种基金the National Natural Science Foundation of China(82130064,81825015,U22A20337 and 32000119)the Key Biosafety Science and Technology Program of Hubei Jiangxia Laboratory(JXBS001).
文摘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.
文摘This study aimed to analyze frequencies of flavor detection signals occurring in any of the three respiratory phases and either of the two masticatory phases. Flavors of three fruity (grape, orange, and strawberry) gummy candies in the mouth were detected after chewing in 24 young healthy participants. The results revealed that: 1) more detection signals occurred in the expiratory phase than in the inspiratory or pausing phases and 2) more detection signals occurred in the jaw-closing phase than in the jaw-opening phase. Statistical analysis showed that the difference between the frequencies among the three respiratory phases was significant (P < 0.001) but not between the two masticatory phases. Further analysis showed that the frequencies occurring within individual respiratory phases were not significantly biased. The present results suggest that flavor detection during chewing depends more on the expiratory phase rather than the inspiratory and pausing phases, whereas detection is dependent to a lesser extent on either of the masticatory phases.
