[TOC]
# Avian reovirus S1 gene
## Introduction
The avian reovirus (ARV) belonging to the Orthoreovirus genus, is a non-enveloped virus with a double stranded RNA segmented genome. These characteristics make ARV prone to mutation, recombination and re-assortment events generating molecular variants (ARVv) through the time that might change their antigenicity and thus pathogenicity compared with classic and vaccine strains (5,14,15,17).

ARV structure *source: https://viralzone.expasy.org/105

The ten ARV segments are classified into three large (L1, L2, L3), three medium (M1, M2, M3), and four small (S1, S2, S3, S4) genes (12,16).
## S1 gene
The S1(1,644 nucleotdes) is a tricistronic gene, which means that encodes exons for three viral proteins: p10 (98 aa), p17 (146 aa) and sigma C (σC, 326 aa) proteins(2).

ARV genome *source: https://viralzone.expasy.org/105

## Sigma C protein
σC is one of the most variable proteins and plays a key role in mediating cell attachment (8) and eliciting type-specific neutralizing antibodies (2,10). Therefore, the σC encoding gene is targeted in ARV molecular characterizations (1,4,6,7,14,19).
σC C protein *source:https://www.rcsb.org/structure/2VRS#entity-1

Since 2003, the emergence of ARVv strains have been reported different parts of the world. To date, seven σC genotypes of avian reoviruses have been registered globally (1,4,6,7,9,13–15,19).
In production settings, the disease control and prevention in meat type poultry is attempted by using commercial live attenuated and autogenous inactivated vaccines but their effectiveness is threatened due to the continuous change of circulating ARV serotypes (3,11,14,18).

## Research questions
1. Why S1 gene is considered the most variable gene in the ARV genome?
2. Are p10 and p17 variable proteins?

## Data types for answer the research questions
1. S1 gene expression between different ARV strains
2. Common mutations of S1

## Databases

### 1) ViralZone
*source https://viralzone.expasy.org

ViralZone is a free and accesible database that belongs to the Swiss Institute of Bioinformatics (SIB). It is a database with secondary characteristics. It store and share information about viral taxonomy which address questions about viral diversity. The data is stored in ordered files and links that import other database content. This site also links relevant content about genomics and proteomics to GenBank and UniProtKB/Swiss-Prot databases respectivelly. It contain an interactive and friendly tool to search contents about taxonomic classification, morphology, virus entry transcription, replication, translation and virus exit mechanisms. The data can be computationally accessed computationally but not directly downloaded. Also, the user can navigate between host-virus interactions, virus genome evolution, replication cycles, etc. Interestingly, ViralZone is well know by their virion diagrams and pictures which can be found in important virology books. The pictures are licensed under a Creative Commons Attribution 4.0 International License. Data can be used and shared under citation agreement. This database host about 702 virus species including the avian reovirus.
#### Paper citing Viralzone
Wollenberg, D. J. V. D., Hengel, S. K. V. D., Dautzenberg, I. J., Kranenburg, O., & Hoeben, R. C. (2009). Modification of mammalian reoviruses for use as oncolytic agents. Expert opinion on biological therapy, 9(12), 1509-1520.

The researchers used this data base to show pictures and diagrams related to mamalian reoviruses.

##### Avian reovirus gene expression in VralZone
https://viralzone.expasy.org/105

### 2) Viprbrc
*source https://www.viprbrc.org

The Virus Pathogen Resource (Viprbrc) is a daabase funded by the U.S. National Institute of Allergy and Infectious Diseases and the National Institutes of Health. It is a database with secondary characteristics. It store and share information about viral sequences, protein structure analysis. It adresses questions about genomics and viral phenotype studies in general. The data is stored in ordered files and references that import other database content.
The database also generate its own information (primary characteristics) about mature peptides and sequence feature variant types using their own algoritms and programs. It imports information from public databases (NCBI, UniProt, Immune epitope database and Protein Data Bank). It has a search tool for accessing the data and it can be be accessed computationally accessed and directly downloaded. Metadata can be analyzed and dowloaded in different formats. Data can be used and shared under citation agreement.
It contains information about more than 6,000 species , 900,000 genomes and more that 3 million viral proteins wich 3.4% belong to the *Reoviridae* family.

#### Paper citing Viprbrc
Grifoni, A., Sidney, J., Zhang, Y., Scheuermann, R. H., Peters, B., & Sette, A. (2020). A sequence homology and bioinformatic approach can predict candidate targets for immune responses to SARS-CoV-2. Cell host & microbe.

The researchers used this data base to gather information about epitope sites from other coronaviruses, and to map regions in the SARS-CoV-2 sequences to predict epitopes.

##### Avian reovirus proteins in Viprbrc
https://www.viprbrc.org/brc/vipr_protein_search.spg?method=SubmitForm&decorator=reo&selectionContext=1602606732079&sortBy=lower(spProtName2)&sortOrder=asc

## Comparison of the two selected databases

| Features | ViralZone | Viprbrc |
| ---------------- | ---------------------------------------------------------------------------------------- | ---------------------------------------------------------------------------------------------- |
| Organization | Well organize, crear index, didactic | Not well organized, not clear index |
| Accesibility | Easy to access and search in each page | Easy search and advanced search tool |
| Intuitivity | Very intuitive, easy for general public | Somehow intuitive, oriented to researchers |
| Data curation | by C. Hulo and P. Masson. Last update: June, 2020. | By a research group not mentioned. Last update: October, 2020 |
| Data integration | It links only certain genetic sequences with NCBI and certain protein codes with UniProt | It integrates multuple databases: NCBI, UniProt, Immune epitope database and Protein Data Bank |
| Avian Reovirus (ARV) information | General information is well explained, good virion pictures, but it lack about updated information. Information about variant is poorly described and referenced. There is a very basic explanation about S1 gene and there is no information about exons or product sizes and structures | General information is not well explained. It Doesn't show virion pictures, but S1 gene structure is well described and it contains information about variant strains related with this gene. It shows a variety of genomes (2,400) for diferent proteins like Sigma C and other protein sequences. The database Viprbrc is fits better to help answer my research questions. |

In my opinion the two most important characteristic of these databases are data curation that should be updated frequenly by trained people and the organization of the information which should be easy to access trough advanced search system.

## References
1. Ayalew, L. E., A. Gupta, J. Fricke, K. A. Ahmed, S. Popowich, B. Lockerbie, S. K. Tikoo, D. Ojkic, and S. Gomis. Phenotypic, genotypic and antigenic characterization of emerging avian reoviruses isolated from clinical cases of arthritis in broilers in Saskatchewan, Canada. Sci. Rep. 2017.
2. Benavente, J., and J. Martínez-Costas. Avian reovirus: Structure and biology. Virus Res. 2007.
3. Bernier, G., and A. Silim. Serological and pathogenic characterization of avian reoviruses isolated in Quebec. Avian Pathol. 1991.
4. Egaña-Labrin, S., R. Hauck, A. Figueroa, S. Stoute, H. L. Shivaprasad, M. Crispo, C. Corsiglia, H. Zhou, C. Kern, B. Crossley, and R. A. Gallardo. Genotypic Characterization of Emerging Avian Reovirus Genetic Variants in California. Sci. Rep. 9. 2019.
5. Goldenberg, D., M. Pasmanik-Chor, M. Pirak, N. Kass, A. Lublin, A. Yeheskel, D. Heller, and J. Pitcovski. Genetic and antigenic characterization of sigma C protein from avian reovirus. Avian Pathol. 2010.
6. Kant, A., F. Balk, L. Born, D. Van Roozelaar, J. Heijmans, A. Gielkens, and A. Ter Huurne. Classification of Dutch and German avian reoviruses by sequencing the σC protein. Vet. Res. 2003.
7. Lu, H., Y. Tang, P. A. Dunn, E. A. Wallner-Pendleton, L. Lin, and E. A. Knoll. Isolation and molecular characterization of newly emerging avian reovirus variants and novel strains in Pennsylvania, USA, 2011-2014. Sci. Rep. 2015.
8. Martínez-Costas, J., A. Grande, R. Varela, C. García-Martínez, and J. Benavente. Protein architecture of avian reovirus S1133 and identification of the cell attachment protein. J. Virol. 1997.
9. Palomino-Tapia, V., D. Mitevski, T. Inglis, F. van der Meer, and M. F. Abdul-Careem. Molecular characterization of emerging avian reovirus variants isolated from viral arthritis cases in Western Canada 2012–2017 based on partial sigma (σ)C gene. Virology. 2018.
10. Pitcovski, J., and S. M. Goyal. Avian Reovirus Infections. In: Diseases of Poultry. 2020.
11. Rosenberger, S. C. , Rosenberger, J.K., Markis, M., R. J. P. Characterization of Recent (2011-2012) Reovirus Isolates from Broiler and Turkey Flocks Presenting with Viral Arthritis and Tenosynovitis Using In Vitro Antibody Dependent Virus Neutralization Assays. In: The American Association of Avian Pathologists (AAAP) Annual meeting. 2013.
12. Schnitzer, T. J. Protein coding assignment of the S genes of the avian reovirus S1133. Virology. 1985.
13. Sellers, H. S., Day, S. L., L. E. Genotypic classification of avian reoviruses. In: The American Association of Avian Pathologists (AAAP) Annual meeting. pp. 58–59. 2019.
14. Sellers, H. S. Current limitations in control of viral arthritis and tenosynovitis caused by avian reoviruses in commercial poultry. Vet. Microbiol. 2017.
15. Troxler, S., P. Rigomier, I. Bilic, D. Liebhart, I. Prokofieva, B. Robineau, and M. Hess. Identification of a new reovirus causing substantial losses in broiler production in France, despite routine vaccination of breeders. Vet. Rec. 2013.
16. Varela, R., and J. Benavente. Protein coding assignment of avian reovirus strain S1133. J. Virol. 1994.
17. Vasserman, Y., D. Eliahoo, E. Hemsani, N. Kass, G. Ayali, S. Pokamunski, and J. Pitcovski. The influence of reovirus sigma C protein diversity on vaccination efficiency. Avian Dis. 2004.
18. Wood, G. W., R. A. J. Nicholas, C. N. Hebert, and D. H. Thornton. Serological comparisons of avian reoviruses. J. Comp. Pathol. 1980.
19. Zhong, L., L. Gao, Y. Liu, K. Li, M. Wang, X. Qi, Y. Gao, and X. Wang. Genetic and pathogenic characterisation of 11 avian reovirus isolates from northern China suggests continued evolution of virulence. Sci. Rep. 2016.