Cryo-electron Microscopy Structures of Novel Viruses from Mud Crab Scylla paramamosain with Multiple Infections
JOURNAL OF VIROLOGY
Authors: Gao, Yuanzhu; Liu, Shanshan; Huang, Jiamiao; Wang, Qianqian; Li, Kunpeng; He, Jian; He, Jianguo; Weng, Shaoping; Zhang, Qinfen
Abstract
Viruses associated with sleeping disease (SD) in crabs cause great economic losses to aquaculture, and no effective measures are available for their prevention. In this study, to help develop novel antiviral strategies, single-particle cryoelectron microscopy was applied to investigate viruses associated with SD. The results not only revealed the structure of mud crab dicistrovirus (MCDV) but also identified a novel mud crab tombus-like virus (MCTV) not previously detected using molecular biology methods. The structure of MCDV at a 3.5-angstrom resolution reveals three major capsid proteins (VP1 to VP3) organized into a pseudo-T = 3 icosahedral capsid, and affirms the existence of VP4. Unusually, MCDV VP3 contains a long C-terminal region and forms a novel protrusion that has not been observed in other dicistrovirus. Our results also reveal that MCDV can release its genome via conformation changes of the protrusions when viral mixtures are heated. The structure of MCTV at a 3.3-angstrom resolution reveals a T = 3 icosahedral capsid with common features of both tombusviruses and nodaviruses. Furthermore, MCTV has a novel hydrophobic tunnel beneath the 5-fold vertex and 30 dimeric protrusions composed of the P-domains of the capsid protein at the 2-fold axes that are exposed on the virion surface. The structural features of MCTV are consistent with a novel type of virus. IMPORTANCE Pathogen identification is vital for unknown infectious outbreaks, especially for dual or multiple infections. Sleeping disease (SD) in crabs causes great economic losses to aquaculture worldwide. Here we report the discovery and identification of a novel virus in mud crabs with multiple infections that was not previously detected by molecular, immune, or traditional electron microscopy (EM) methods. High-resolution structures of pathogenic viruses are essential for a molecular understanding and developing new disease prevention methods. The three-dimensional (3D) structure of the mud crab tombus-like virus (MCTV) and mud crab dicistrovirus (MCDV) determined in this study could assist the development of antiviral inhibitors. The identification of a novel virus in multiple infections previously missed using other methods demonstrates the usefulness of this strategy for investigating multiple infectious outbreaks, even in humans and other animals.
Immunogenicity of Oral Polio Vaccine and Salk Inactive Polio Vaccine Against Xinjiang Imported Type 1 Wild Poliovirus
CLINICAL INFECTIOUS DISEASES
Authors: Yan, Dongmei; Wang, Dongyan; Zhu, Shuangli; Zhang, Yong; Li, Xiaolei; Tang, Haishu; Guan, Jing; Xu, Wenbo
Abstract
Background: An outbreak of an imported Type 1 wild poliovirus from Pakistan occurred in the Xinjiang Uygur Autonomous Region of China in 2011, although the local immunity status of the oral polio vaccine (OPV) was relatively satisfied. Methods: Neutralizing antibody titers against the Xinjiang strain and Sabin 1 strain were measured in 237 sera from 3 groups of fully OPV-vaccinated persons and 1 group of infants fully vaccinated with the inactive polio vaccine (IPV). Additionally, 17 sera collected from 1 Xinjiang poliomyelitis case and his 16 contacts were also tested. Genomic sequencing was conducted the Xinjiang strain. Results: The antibody titers against the Xinjiang strain in each of 237 sera were significantly lower than those against the Sabin 1 strain. Notably, 40.0% of children in Group 1 were seronegative against the Xinjiang strain, which indicated that they might play an important role in wild poliovirus transmission, although their antibody titers against the Sabin 1 strain varied between 1:8 and 1:512. Meanwhile, serological results of the Xinjiang poliomyelitis case and his contacts also provided evidence that a proportion of OPV-vaccinated children had indeed been involved in the transmission chain of the Xinjiang outbreak. Genomic sequencing indicated that the Xinjiang strain was greatly distinguishable from the Sabin 1 strain in neutralizing antigenic sites. Conclusion: The lack of neutralizing antibodies against the Xinjiang strain in persons vaccinated by OPV may be associated with the transmission of Type 1 wild poliovirus in Xinjiang. Using Salk IPV along with OPV might be considered in a wild poliovirus outbreak response, especially in the countries which continued to have persistent wild poliovirus circulation.