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Inter- and intragenus structural variations in caliciviruses and their functional implications.

ABSTRACT: The family Caliciviridae is divided into four genera and consists of single-stranded RNA viruses with hosts ranging from humans to a wide variety of animals. Human caliciviruses are the major cause of outbreaks of acute nonbacterial gastroenteritis, whereas animal caliciviruses cause various host-dependent illnesses with a documented potential for zoonoses. To investigate inter- and intragenus structural variations and to provide a better understanding of the structural basis of host specificity and strain diversity, we performed structural studies of the recombinant capsid of Grimsby virus, the recombinant capsid of Parkville virus, and San Miguel sea lion virus serotype 4 (SMSV4), which are representative of the genera Norovirus (genogroup 2), Sapovirus, and Vesivirus, respectively. A comparative analysis of these structures was performed with that of the recombinant capsid of Norwalk virus, a prototype member of Norovirus genogroup 1. Although these capsids share a common architectural framework of 90 dimers of the capsid protein arranged on a T=3 icosahedral lattice with a modular domain organization of the subunit consisting of a shell (S) domain and a protrusion (P) domain, they exhibit distinct differences. The distally located P2 subdomain of P shows the most prominent differences both in shape and in size, in accordance with the observed sequence variability. Another major difference is in the relative orientation between the S and P domains, particularly between those of noroviruses and other caliciviruses. Despite being a human pathogen, the Parkville virus capsid shows more structural similarity to SMSV4, an animal calicivirus, suggesting a closer relationship between sapoviruses and animal caliciviruses. These comparative structural studies of caliciviruses provide a functional rationale for the unique modular domain organization of the capsid protein with an embedded flexibility reminiscent of an antibody structure. The highly conserved S domain functions to provide an icosahedral scaffold; the hypervariable P2 subdomain may function as a replaceable module to confer host specificity and strain diversity; and the P1 subdomain, located between S and P2, provides additional fine-tuning to position the P2 subdomain.

SUBMITTER: Chen R

PROVIDER: S-EPMC416503 | biostudies-literature | 2004 Jun

REPOSITORIES: biostudies-literature

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Inter- and intragenus structural variations in caliciviruses and their functional implications.

Chen Rong R Neill John D JD Noel Jacqueline S JS Hutson Anne M AM Glass Roger I RI Estes Mary K MK Prasad B V Venkataram BV

Journal of virology 20040601 12

The family Caliciviridae is divided into four genera and consists of single-stranded RNA viruses with hosts ranging from humans to a wide variety of animals. Human caliciviruses are the major cause of outbreaks of acute nonbacterial gastroenteritis, whereas animal caliciviruses cause various host-dependent illnesses with a documented potential for zoonoses. To investigate inter- and intragenus structural variations and to provide a better understanding of the structural basis of host specificity ...[more]

PMID: 15163740

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Project description:BackgroundThe aim of this study was to determine the--largely unexplored--extent of systematic variation in the work disability assessment by Dutch insurance physicians (IPs) of employees on long-term sick leave, and to ascertain whether this variation was associated with the individual characteristics and opinions of IPs.MethodsIn March 2008 we conducted a survey among IPs on the basis of the 'Attitude--Social norm--self-Efficacy' (ASE) model. We used the ensuing data to form latent variables for the ASE constructs. We then linked the background variables and the measured constructs for IPs (n = 199) working at regional offices (n = 27) to the work disability assessments of clients (n = 83,755) and their characteristics. These assessments were carried out between July 2003 and April 2008. We performed multilevel regression analysis on three important assessment outcomes: No Sustainable Capacity or Restrictions for Working Hours (binominal), Functional Incapacity Score (scale 0-6) and Maximum Work Disability Class (binominal). We calculated Intra Class Correlations (ICCs) at IP level and office level and explained variances (R2) for the three outcomes. A higher ICC reflects stronger systematic variation.ResultsThe ICCs at IP level were approximately 6% for No Sustainable Capacity or Restrictions for Working Hours and Maximum Work Disability Class and 12% for Functional Incapacity Score. Background IP variables and the measured ASE constructs for physicians contributed very little to the variation--at most 1%. The ICCs at office level ranged from 0% to around 1%. The R2 was 11% for No Sustainable Capacity or Restrictions for Working Hours, 19% for Functional Incapacity Score and 37% for Maximum Work Disability Class.ConclusionOur study uncovered small to moderate systematic variations in the outcome of disability assessments in the Netherlands. However, the individual characteristics and opinions of insurance physicians have very little impact on these variations. Our findings provided no indications of other reasons for these variations. They may be related to different work routines or to different views on the workload of a 'normal' employee. If so, they could be reduced by well-developed and comprehensively implemented guidelines. Therefore, further research is needed.

Dataset Information

Inter- and intragenus structural variations in caliciviruses and their functional implications.

Publications

Inter- and intragenus structural variations in caliciviruses and their functional implications.

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