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Specific Sequence of a Beta Turn in Human La Protein May Contribute to Species Specificity of Hepatitis C Virus

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Title Specific Sequence of a Beta Turn in Human La Protein May
Contribute to Species Specificity of Hepatitis C Virus
 
Creator Kumar, Anuj
Manna, Asit Kumar
Ray, Upasana
Mullick, Ranajoy
Basu, Gautam
Das, Saumitra
Roy, Siddhartha
 
Subject Structural Biology & Bioinformatics
 
Description Human La protein is known to be an essential host factor for translation and replication of hepatitis C virus (HCV) RNA. Previously,we have demonstrated that residues responsible for interaction of human La protein with the HCV internal ribosomal entry site (IRES)around the initiator AUG within stem-loop IV form a�-turn in the RNA recognition motif (RRM) structure. In this study, sequence
alignment and mutagenesis suggest that the HCVRNA-interacting�-turn is conserved only in humans and chimpanzees, the species primarily known to be infected by HCV. A 7-mer peptide corresponding to the HCV RNA-interacting region of human La inhibits HCV translation, whereas another peptide corresponding to the mouse La sequence was unable to do so. Furthermore, IRES-mediated
translation was found to be significantly high in the presence of recombinant human La protein in vitro in rabbit reticulocyte lysate. We observed enhanced replication with HCV sub genomic and full-length replicons upon overexpression of either human La protein or a chimeric mouse La protein harboring a human La�-turn sequence in mouse cells. Taken together, our results raise the possibility of creating an immune competent HCV mouse model using human-specific cell entry factors and a humanized form of La protein
 
Publisher American Society for Microbiology
 
Date 2014
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2195/1/JOURNAL_OF_VIROLOGY__V_88___(_8_)_4319%2D4327;2014[131].pdf
Kumar, Anuj and Manna, Asit Kumar and Ray, Upasana and Mullick, Ranajoy and Basu, Gautam and Das, Saumitra and Roy, Siddhartha (2014) Specific Sequence of a Beta Turn in Human La Protein May Contribute to Species Specificity of Hepatitis C Virus. Journal of Virology, 88 (8). pp. 4319-4327.
 
Relation http://dx.doi.org/10.1128/JVI.00049-14
http://www.eprints.iicb.res.in/2195/