Filovirade - Ebola virus

Filovirade -

The family Filovirade, the negative stranded RNA viruses, is characterized by their enveloped, non-segmented, and filamentous forms and these viruses grow fast in monocytes, macrophages, fibro-lasts, and endothelial cells during infection. Filovirade causes serious viral hemorrhagic fever which can bring high fever, bleeding disorders, shock and death in many cases. There are currently no vaccines or other treatment for this deadly disease.

Ebola virus and Marburg virus is in the family Filovirade and they are both category A bioweapon organisms. Ebola virus nucleoprotein (NP) is consists of 739aa that can be divided into C-terminal half (about 350aa) and N-erminal  (about 400aa) [2].

 

The N-terminal region plays a central role on binding RNA binding and C-erminal region is responsible for the interaction with the matrix protein VP 40 which is important for structure building. Ebola virus NP was found to interact with glycan binding proteins and assembles into helical structures Similar to Marburg virus NP.

 

Marburg virus particle is consists of seven structure proteins. Marburg virus nucleo complex is composed of four of them, NP, VP35, VP30 and L. NP, the leading nucleocapsid protein, form tubular nucleocapsid structure which is the first step in nucleocapsid assembly. So it is important to understand different functions of NP during viral morphogenesis, replication and transcription.

 

Ebola virus -

 

Filovirus family was discovered around 1960s to 1970s. Since they are extremely deadly and have no cure, Study’s about their structures and characteristics are held in various ways.

Ebola virus nucleoprotein NP and VP, which is an essential element of the nucleocapsid aregenerally being studied. The research Unique Region of Ebola Virus NP Confers Aberrant Migration and Mediates Its Incorporation into Virions [7] indicates that two regions of this protein, amino acids 439 to492 and 589 to 739 determine the aberrant migration and mediates its incorporation into virions.
Another research revealed that the COOH-terminal domain of Ebolavirus NP is a key attractant for antibodies and enables sandwich immunoassays to be quickly generated using a
single antibody clone [5].
High-throughput virtual screening and docking studies of matrix protein vp40 of ebola virus [6] includes the identification of potential inhibitors against Ebola virus matrix protein VP40
using high throughput virtual screening and three tiered docking strategy and subjecting shortlisted compounds for ADME analysis. The research concludes that the ligand ASN03576800 could be a potential inhibitor for VP40 in viral assembly and budding process considering its good glide score and contact with the specific amino acid residue Arg134.
The assembly of Ebola virus nucleocapsid requires virion-associated proteins 35 and 24 and posttranslational modification of nucleoprotein [4] indicates that When expression vectors encoding numerous viral genes were cotransfected into the highly transfectable 293 human renal epithelial cell line, considerable assembly of intracellular Ebola virus-like particles was observed. 

By analyzing various combinations of viral genes and buoyant density gradient sedimentation, virion-associated proteins 35 and 24 and posttranslational modification of nucleoprotein were found to be necessary and sufficient for Ebola nucleocapsid assembly.



reference 
[1] Characterization of the Ebola virus nucleoprotein–RNA complex. Takeshi Noda1, Kyoji Hagiwara2, Hiroshi Sagara3

     and Yoshihiro Kawaoka. iternational Research Center for Infectious Diseases, Institute of Medical Science,     
     University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
[2] Filoviridae: Marburg and Ebola viruses. In Fields Virology, Sanchez et al., 2007
[3] Nucleocapsid formation and RNA synthesis of Marburg virus is dependent on two

    coiled coil motifs in the nucleoprotein. Andrea DiCarlo12, Peggy

    Möller13, Angelika Lander14, Larissa Kolesnikova14 and Stephan Becker14*

    Virology Journal 2007, 4:105 doi:10.1186/1743-422X-4-105
[4] The assembly of Ebola virus nucleocapsid requires virion-associated proteins 35 and

    24 and posttranslational modification of nucleoprotein. Huang Y, Xu L, Sun

    Y, Nabel GJ. Vaccine Research Center, National Institutes of Allergy and Infectious
    Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
[5] Ebolavirus Nucleoprotein C-Termini Potently Attract Single Domain Antibodies

    Enabling Monoclonal Affinity Reagent Sandwich Assay (MARSA) Formulation

    Laura J. Sherwood and Andrew Hayhurst. PLoS ONE 8(4): e61232. doi:10.1371/journal.pone.0061232
[6] High-throughput virtual screening and docking studies of matrix protein vp40 of

    ebola virus. Thangaraju Tamilvanan & Waheeta Hopper. Department of

    Bioinformatics, School of Bioengineering, Faculty of Engineering & Technology,

    SRM University, Kattankulathur, 603203, Tamil Nadu, India
[7] A Filovirus-Unique Region of Ebola Virus Nucleoprotein Confers. Aberrant

    Migration and Mediates Its Incorporation into Virions. Wei Shi,1 Yue Huang.
    Vaccine Research Center, NIAID, National Institutes of Health, Bldg. 40, Rm. 4502,

    MSC-3005, 40 Convent Dr., Bethesda, MD 20892-3005, USA.

 

 

- 김유신 (HKICEAS-723, 12. 9. 2013)