5c4w
Crystal structure of coxsackievirus A16
Structural highlights
FunctionI3W9E1_9ENTO Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).[SAAS:SAAS000199_004_016611] Protein 3C is a cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind co-operatively to the protease (By similarity).[SAAS:SAAS000199_004_042266] RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).[SAAS:SAAS000199_004_010047] Publication Abstract from PubMedEnterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the primary causes of the epidemics of hand-foot-and-mouth disease (HFMD) which affect more than a million children in China each year, and lead to hundreds of deaths. Although there has been progress with vaccines for EV71, development of a CVA16 vaccine has proved more challenging, and the EV71 vaccine does not give useful cross-protection, despite the capsid proteins of the two viruses sharing about 80% sequence identity. The structural details of the expanded forms of the capsids, which possess non-native antigenicity are now well understood, but high resolution information for the native antigenic form of CVA16 has been missing. We here remedy this with high resolution X-ray structures of both mature and natural empty CVA16 particles and also of empty recombinant virus-like particles of CVA16 produced in insect cells, a potential vaccine antigen. All three structures are unexpanded native particles and antigenically identical. The recombinant particles have recruited a lipid moiety to stabilise the native antigenic state that is different to that used in a natural virus infection. As expected the mature CVA16 virus is similar to EV71, however structural and immunogenic comparisons highlight differences, which may have implications for vaccine production. IMPORTANCE: Hand-foot-and-mouth disease is a serious public health threat to children in Asian-Pacific countries, resulting in millions of cases. EV71 and CVA16 are the two dominant causative agents of a disease that, whilst usually mild, can cause severe neurological complications, leading to hundreds of deaths. EV71 vaccines do not provide protection against CVA16. A CVA16 vaccine or bivalent EV71/CVA16 vaccine is therefore urgently needed. We report atomic structures for the mature CVA16 virus, natural empty particles, and a recombinant CVA16 virus-like particle that does not contain the viral genome. All three particles have similar structures and identical antigenicity. The recombinant particles produced in insect cells (a system suitable for making vaccine antigen) are stabilised by recruiting from the insect cells a small molecule different to that used by the virus in a normal infection. We present structural and immunogenic comparisons with EV71 to facilitate structure-based drug-design and vaccine development. Structures of coxsackievirus A16 capsids with native antigenicity, implications for particle expansion, receptor binding and immunogenicity.,Ren J, Wang X, Zhu L, Hu Z, Gao Q, Yang P, Li X, Wang J, Shen X, Fry EE, Rao Z, Stuart DI J Virol. 2015 Aug 12. pii: JVI.01102-15. PMID:26269176[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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