Two consecutive central proline residues of internal fusion peptide of mouse hepatitis virus spike protein serves important role in neural cell fusion

Kishore, Abhinoy (2015) Two consecutive central proline residues of internal fusion peptide of mouse hepatitis virus spike protein serves important role in neural cell fusion. PhD thesis, Indian Institute of Science Education and Research Kolkata.

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Abstract

Genetic complexity together with variability in the pathology, symptoms and clinical course of MS suggests the possibility of multiple disease initiating pathways. Disease heterogeneity may account for the difficulty in identifying etiological factor and therapeutic targets of MS still experimental possibility of disease these subtypes has limited due to lack of appropriate animal model. EAE and MHV demyelinating disease in mice have been quietly used as a model of MS while EAE is useful in dissecting the role or T cell mediated myelin damage viral model are helpful in understanding in direct CNS cellular injury and demyelination that does not require an intact immune system. Infection of mice with neurotropic strain of MHV or its isogenic spike strain RSA59 induces meningoencephalitis and chronic inflammatory demyelination whereas another very closely strain MHV-2 or its isogenic recombinant strain RSMHV2 (isogenic for all the genes except spike protein) can cause encephalitis but unable to cause demyelination and axonal loss. Spike protein is one of the major determinant neuroinflammatory demyelination and axonal loss spike protein can be considered as one of the target for the therapeutic potential for its property to bind to host neural cell directly. Our studies aim to understand and determine the possible role of spike mediated fusogenicty in the cell to cell fusion of enveloped virus like MHVA59. While MHV-A59/RSA59, can cause cell to cell fusion both in vivo or in vitro MHV2/RSMHV2 are impaired to in cell to cell fusion. Furthermore my studies confirmed that two consecutive cis proline in silico and in vitro may play an important role in the cell cell fusion a hydrophobic stretch of amino acids with two proline at the centre could be the minimal essential motif required for virus host interaction with or without involving the cleavage signal site. To confirm the role of two consecutive proline in the fusogenic property this is first time my study illusturated the significance of cis proline in MHV mediated cell to cell fusion. Further biophysical analysis this fusion peptide should be geared to give the insight into the mechanism of interaction between fusion protein and membrane interaction.

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