Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
June-2016 Volume 13 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June-2016 Volume 13 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Sequence analysis of the L protein of the Ebola 2014 outbreak: Insight into conserved regions and mutations

  • Authors:
    • Gohar Ayub
    • Yasir Waheed
  • View Affiliations / Copyright

    Affiliations: Department of Health Biotechnology, Atta‑ur‑Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad 44000, Pakistan
  • Pages: 4821-4826
    |
    Published online on: April 15, 2016
       https://doi.org/10.3892/mmr.2016.5145
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The 2014 Ebola outbreak was one of the largest that have occurred; it started in Guinea and spread to Nigeria, Liberia and Sierra Leone. Phylogenetic analysis of the current virus species indicated that this outbreak is the result of a divergent lineage of the Zaire ebolavirus. The L protein of Ebola virus (EBOV) is the catalytic subunit of the RNA‑dependent RNA polymerase complex, which, with VP35, is key for the replication and transcription of viral RNA. Earlier sequence analysis demonstrated that the L protein of all non‑segmented negative‑sense (NNS) RNA viruses consists of six domains containing conserved functional motifs. The aim of the present study was to analyze the presence of these motifs in 2014 EBOV isolates, highlight their function and how they may contribute to the overall pathogenicity of the isolates. For this purpose, 81 2014 EBOV L protein sequences were aligned with 475 other NNS RNA viruses, including Paramyxoviridae and Rhabdoviridae viruses. Phylogenetic analysis of all EBOV outbreak L protein sequences was also performed. Analysis of the amino acid substitutions in the 2014 EBOV outbreak was conducted using sequence analysis. The alignment demonstrated the presence of previously conserved motifs in the 2014 EBOV isolates and novel residues. Notably, all the mutations identified in the 2014 EBOV isolates were tolerant, they were pathogenic with certain examples occurring within previously determined functional conserved motifs, possibly altering viral pathogenicity, replication and virulence. The phylogenetic analysis demonstrated that all sequences with the exception of the 2014 EBOV sequences were clustered together. The 2014 EBOV outbreak has acquired a great number of mutations, which may explain the reasons behind this unprecedented outbreak. Certain residues critical to the function of the polymerase remain conserved and may be targets for the development of antiviral therapeutic agents.
View Figures

Figure 1

Figure 2

View References

1 

Sanchez A, Geisbert TW and Feldmann H: Filoviridae: Marburg and ebola viruses. Fields Virology. Knipe DM and Howley PM: Lippincott Williams and Wilkins; Philadelphia, PA: pp. 1409–1448. 2007

2 

Kuhn JH, Becker S, Ebihara H, Geisbert TW, Johnson KM, Kawaoka Y, Lipkin WI, Negredo AI, Netesov SV, Nichol ST, et al: Proposal for a revised taxonomy of the family Filoviridae: Classification, names of taxa and viruses and virus abbreviations. Arch Virol. 155:2083–2103. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Sanchez A, Kiley MP, Holloway BP and Auperin DD: Sequence analysis of the Ebola virus genome: Organization, genetic elements, and comparison with the genome of Marburg virus. Virus Res. 29:215–240. 1993. View Article : Google Scholar : PubMed/NCBI

4 

Boehmann Y, Enterlein S, Randolf A and Mühlberger E: A reconstituted replication and transcription system for Ebola virus Reston and comparison with Ebola virus Zaire. Virology. 332:406–417. 2005. View Article : Google Scholar : PubMed/NCBI

5 

Waheed Y: Ebola in West Africa: An international medical emergency. Asian Pac J Trop Biomed. 4:673–674. 2014. View Article : Google Scholar

6 

Waheed Y, Bhatti A and Ashraf M: RNA dependent RNA polymerase of HCV: A potential target for the development of antiviral drugs. Infect Genet Evol. 14:247–257. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Waheed Y, Saeed U, Anjum S, Afzal MS and Ashraf M: Development of global consensus sequence and analysis of highly conserved domains of the HCV NS5B prote in. Hepat Mon. 12:e61422012.PubMed/NCBI

8 

Gire SK, Goba A, Andersen KG, Sealfon RS, Park DJ, Kanneh L, Jalloh S, Momoh M, Fullah M, Dudas G, et al: Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science. 345:1369–1372. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Poch O, Blumberg BM, Bougueleret L and Tordo N: Sequence comparison of five polymerases (L proteins) of unsegmented negative-strand RNA viruses: Theoretical assignment of functional domains. J Gen Virol. 71:1153–1162. 1990. View Article : Google Scholar : PubMed/NCBI

10 

Clamp M, Cuff J, Searle SM and Barton GJ: The Jalview Java alignment editor. Bioinformatics. 20:426–427. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Katoh K and Standley DM: Improvements in performance and usability. Mol Biol Evol. 30:772–780. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Nuin PA, Wang Z and Tillier ER: The accuracy of several multiple sequence alignment programs for proteins. BMC bioinformatics. 7:4712006. View Article : Google Scholar : PubMed/NCBI

13 

Tamura K, Stecher G, Peterson D, Filipski A and Kumar S: MEGA6: Molecular evolutionary genetics analysis version 6.0. Mol Biol Evol. 30:2725–2729. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Saitou N and Nei M: A new method for reconstructing phylogenetic trees. Mol Biol Evol. 4:406–425. 1987.PubMed/NCBI

15 

Ng PC and Henikoff S: Predicting deleterious amino acid substitutions. Genome res. 11:863–874. 2001. View Article : Google Scholar : PubMed/NCBI

16 

Marston DA, McElhinney LM, Johnson N, Müller T, Conzelmann KK, Tordo N and Fooks AR: Comparative analysis of the full genome sequence of European bat lyssavirus type 1 and type 2 with other lyssaviruses and evidence for a conserved transcription termination and poly-adenylation motif in the G-L 3′ non-translated region. J Gen Virol. 88:1302–1314. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Volchkov VE, Volchkova VA, Chepurnov AA, Blinov VM, Dolnik O, Netesov SV and Feldmann H: Characterization of the L gene and 5′ trailer region of Ebola virus. J Gen Virol. 80:355–362. 1999. View Article : Google Scholar

18 

Schnell MJ and Conzelmann KK: Polymerase activity of in vitro mutated rabies virus L protein. Virology. 214:522–530. 1995. View Article : Google Scholar : PubMed/NCBI

19 

Blumberg BM, Crowley JC, Silverman JI, Menonna J, Cook SD and Dowling PC: Measles virus L protein evidences elements of ancestral RNA polymerase. Virology. 164:487–497. 1998. View Article : Google Scholar

20 

Ogino T and Banerjee AK: The HR motif in the RNA-dependent RNA polymerase L protein of Chandipura virus is required for unconventional mRNA-capping activity. J Gen Virol. 91:1311–1314. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Ferron F, Longhi S, Henrissat B and Canard B: Viral RNA-polymerases-a predicted 2′-O-ribose methyltransferase domain shared by all Mononegavirales. Trends Biochem Sci. 27:222–224. 2002. View Article : Google Scholar : PubMed/NCBI

22 

Grard G, Biek R, Tamfum JJ, Fair J, Wolfe N, Formenty P, Paweska J and Leroy E: Emergence of divergent Zaire Ebola virus strains in democratic republic of the Congo in 2007 and 2008. J Infect Dis. 204(Suppl 3): S776–S784. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Trunschke M, Conrad D, Enterlein S, Olejnik J, Brauburger K and Mühlberger E: The L-VP35 and L-L interaction domains reside in the amino terminus of the Ebola virus L protein and are potential targets for antivirals. Virology. 441:135–145. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Chandrika R, Horikami SM, Smallwood S and Moyer SA: Mutations in conserved domain I of the Sendai virus L polymerase protein uncouple transcription and replication. Virology. 213:352–363. 1995. View Article : Google Scholar : PubMed/NCBI

25 

Feller JA, Smallwood S, Horikami SM and Moyer SA: Mutations in conserved domains IV and VI of the large (L) subunit of the Sendai virus RNA polymerase give a spectrum of defective RNA synthesis phenotypes. Virology. 269:426–439. 2000. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ayub G and Waheed Y: Sequence analysis of the L protein of the Ebola 2014 outbreak: Insight into conserved regions and mutations. Mol Med Rep 13: 4821-4826, 2016.
APA
Ayub, G., & Waheed, Y. (2016). Sequence analysis of the L protein of the Ebola 2014 outbreak: Insight into conserved regions and mutations. Molecular Medicine Reports, 13, 4821-4826. https://doi.org/10.3892/mmr.2016.5145
MLA
Ayub, G., Waheed, Y."Sequence analysis of the L protein of the Ebola 2014 outbreak: Insight into conserved regions and mutations". Molecular Medicine Reports 13.6 (2016): 4821-4826.
Chicago
Ayub, G., Waheed, Y."Sequence analysis of the L protein of the Ebola 2014 outbreak: Insight into conserved regions and mutations". Molecular Medicine Reports 13, no. 6 (2016): 4821-4826. https://doi.org/10.3892/mmr.2016.5145
Copy and paste a formatted citation
x
Spandidos Publications style
Ayub G and Waheed Y: Sequence analysis of the L protein of the Ebola 2014 outbreak: Insight into conserved regions and mutations. Mol Med Rep 13: 4821-4826, 2016.
APA
Ayub, G., & Waheed, Y. (2016). Sequence analysis of the L protein of the Ebola 2014 outbreak: Insight into conserved regions and mutations. Molecular Medicine Reports, 13, 4821-4826. https://doi.org/10.3892/mmr.2016.5145
MLA
Ayub, G., Waheed, Y."Sequence analysis of the L protein of the Ebola 2014 outbreak: Insight into conserved regions and mutations". Molecular Medicine Reports 13.6 (2016): 4821-4826.
Chicago
Ayub, G., Waheed, Y."Sequence analysis of the L protein of the Ebola 2014 outbreak: Insight into conserved regions and mutations". Molecular Medicine Reports 13, no. 6 (2016): 4821-4826. https://doi.org/10.3892/mmr.2016.5145
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team