Human adenovirus B7(HAdV-B7)causes severe acute lower respiratory tract infections in children.However,neither the child-specific antivirals or vaccines are available,nor the pathogenesis is clear.Autophagy,as part of...Human adenovirus B7(HAdV-B7)causes severe acute lower respiratory tract infections in children.However,neither the child-specific antivirals or vaccines are available,nor the pathogenesis is clear.Autophagy,as part of innate immunity,plays an important role in resistance to viral infection by degrading the virus and promoting the development of innate and adaptive immunity.This study provided evidence that HAdV-B7 infection induced complete autophagic flux,and the pharmacological induction of autophagy decreased HAdV-B7 replication.In this process,the host protein Bcl2-associated athanogene 3(BAG3)mediated autophagy to inhibit the replication of HAdV-B7 by binding to the PPSY structural domain of viral protein pVI through its WW structural domain.These findings further our understanding of the host immune response during viral infection and will help to develop broad anti-HAdV therapies.展开更多
Baculoviridae is a family of large DNA viruses that specifically infect insects. It contains four genera, Alpha-, Beta-,Gamma-, and Deltabaculovirus. Alphabaculovirus is further divided into Group Ⅰ and Ⅱ, and Group...Baculoviridae is a family of large DNA viruses that specifically infect insects. It contains four genera, Alpha-, Beta-,Gamma-, and Deltabaculovirus. Alphabaculovirus is further divided into Group Ⅰ and Ⅱ, and Group Ⅰ appears to be emerged most recently among all baculoviruses. Interestingly, there are 12 Group Ⅰ specific genes that are only found in this lineage. Studying these genes is helpful to understand how baculoviruses evolved. Here, we reported the functional analyzing results of ac73, a function unknown Group Ⅰ specific gene of Autographa californica multiple nucleopolyhedrovirus(Ac MNPV) which is the type species of baculovirus. The AC73 protein encoded by ac73 was found to be expressed during the late stage of infection and incorporated into the nucleocapsids of budded virus(BV) and occlusionderived virus(ODV). In infected cells, AC73 resided mainly in the ring zone region of the nucleus, and appeared to be assembled into occlusion bodies(OBs). The ac73 knockout and repaired viruses were constructed and studied by in vitro and in vivo infection. Although ac73 was not essential for BV and ODV or OB formation, the BV titer and viral infectivity in insect larvae of ac73 knockout Ac MNPV decreased by about 5–8 and 3–4 fold compared to those of wild type virus,respectively, suggesting ac73 contributed to infectious BV production and viral infectivity in vivo. This research provides new insight into the function of this Group I specific gene.展开更多
基金This work was supported by the National Natural Science Foundation of China(No.82072266)the CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-026).
文摘Human adenovirus B7(HAdV-B7)causes severe acute lower respiratory tract infections in children.However,neither the child-specific antivirals or vaccines are available,nor the pathogenesis is clear.Autophagy,as part of innate immunity,plays an important role in resistance to viral infection by degrading the virus and promoting the development of innate and adaptive immunity.This study provided evidence that HAdV-B7 infection induced complete autophagic flux,and the pharmacological induction of autophagy decreased HAdV-B7 replication.In this process,the host protein Bcl2-associated athanogene 3(BAG3)mediated autophagy to inhibit the replication of HAdV-B7 by binding to the PPSY structural domain of viral protein pVI through its WW structural domain.These findings further our understanding of the host immune response during viral infection and will help to develop broad anti-HAdV therapies.
基金supported by the grants from the Key Research Project of Frontier Science (QYZDJ-SSWSMC021)the Strategic Priority Research Program (grant No. XDB11030400) from the Chinese Academy of Sciencesthe grants (No. 31621061) from the National Natural Science Foundation of China
文摘Baculoviridae is a family of large DNA viruses that specifically infect insects. It contains four genera, Alpha-, Beta-,Gamma-, and Deltabaculovirus. Alphabaculovirus is further divided into Group Ⅰ and Ⅱ, and Group Ⅰ appears to be emerged most recently among all baculoviruses. Interestingly, there are 12 Group Ⅰ specific genes that are only found in this lineage. Studying these genes is helpful to understand how baculoviruses evolved. Here, we reported the functional analyzing results of ac73, a function unknown Group Ⅰ specific gene of Autographa californica multiple nucleopolyhedrovirus(Ac MNPV) which is the type species of baculovirus. The AC73 protein encoded by ac73 was found to be expressed during the late stage of infection and incorporated into the nucleocapsids of budded virus(BV) and occlusionderived virus(ODV). In infected cells, AC73 resided mainly in the ring zone region of the nucleus, and appeared to be assembled into occlusion bodies(OBs). The ac73 knockout and repaired viruses were constructed and studied by in vitro and in vivo infection. Although ac73 was not essential for BV and ODV or OB formation, the BV titer and viral infectivity in insect larvae of ac73 knockout Ac MNPV decreased by about 5–8 and 3–4 fold compared to those of wild type virus,respectively, suggesting ac73 contributed to infectious BV production and viral infectivity in vivo. This research provides new insight into the function of this Group I specific gene.
