nemoci-sympt/VIROLOGIE/nipah/stavba
NiV belongs to the Henipavirus genus ¨
- Within the Paramyxoviridae
- Enveloped,
- Non-segmented,
- Negative-sense RNA viruses
- Genomes code for six structural proteins:
- Nucleocapsid (N), phosphoprotein (P), matrix protein (M), fusion protein (F), glycoprotein or receptor-binding protein (G), and large protein or RNA polymerase (L).
- Pathogenic to humans
- NiV, measles virus, mumps virus, Hendra virus (HeV), and several parainfluenza viruses
- NiV has a broad host range that includes humans, bats, pigs, sheep, goats, dogs, cats, and horses.
- www.ecdc.europa.eu/en/infectious-disease-topics/z-disease-list/nipah-virus-disease/factsheet-nipah-virus-disease
Mutace
- Malaysian and Bangladeshi/Indian strains
- High degree (79–99%) of sequence similarity
- Structural models using sequences of one strain
- Would be applicable to the other
- Different strains (7 Malaysian, 3 Bangladeshi and 5 Indian) of NiV.
- Amino acid variations
- All protein sequences are of equal length except the V protein whose length varies between the different strains
- The V and W protein have the least sequence conservation (~79%)
- M protein is the most conserved (98.6%)
- Bangladeshi and Indian strains are more similar to one another than they are to the Malaysian sequences
- No variations in the sequence were found close to the peptide inhibitor binding sites on the F, M and G proteins.
- All the mutations (except for Asp252Gly on F protein) on the binding site were conservative
- Similar physico-chemical properties and BLOSUM62 score > = 0
- Non-conservative change (Asp252Gly) in one of the drug/inhibitor binding sites of the F protein
- Not involved in H-bonding with the ligand
- journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0007419
NiV genome
- Encodes six structural proteins
- Glycoprotein (G),
- G protein helps in viral attachment to host cell ephrin receptors
- Fusion protein (F),
- F protein mediates viral fusion
- Matrix protein (M),
- After replication, the M protein homodimerizes and the dimers form arrays at the plasma membrane
- Dimer-dimer interactions induce a curvature in the membrane that enables budding/release of new viral particles
- Nucleoprotein (N),
- RNA-directed RNA polymerase (L),
- Phosphoprotein (P)
- The P protein binds to the N protein
- Maintains it in a soluble form
- Increases its specificity towards viral RNA instead of non-specific cellular RNA
- Three non-structural proteins named W, C and V
- Act against interferon signalling to escape the host immune response
- The N-P protein complex
- Binds the viral RNA forming the nucleocapsid
- This nucleocapsid coated viral RNA acts as a template for viral polymerase L to replicate itself
- The host machinery is then utilized to translate its proteins
- All these proteins
- Are potential targets for rational drug design
- journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0007419
