Análysis of the interaction between the RNA-dependent RNA polymerase (L protein) of Tacaribe virus and its inhibitor the Z-protein

MARINO BUSLJE C, WILDA M, FRANZE-FERNANDEZ MT, DELFINO JM.

Ciudad Autónoma de Buenos Aires, Argentina

Jornada; II Jornadas Iberoamericanas de Bioinformática; 2006

Tacaribe Virus is the prototype of the New World arenavirus and conforms a unique phylogenetic lineage with the South American pathogens causativas of haemorrhagic fever : the viruses Junin, Machupo, Guanarito and Sabia. A model was made of the putative RNA-dependent RNA polymerase (RdRp) encoded in región III of Tacaribe L protein. The structure of the RdRp of hepatitis C virus was used as témplate. The amino acid sequence identity between the target and the témplate is 8.9% and several rounds of modelling were required until no further improvements arose. Región III of TacV- L protein adopts an overall structure common to other viral RdRps, a right hand fold where the finger, palm and thumb domains are immediately recognízable. Although región III was defined as spanning from amino acid residue 1070 to 1475 in Lassa virus L protein, we found that the beginning of the finger domain of región III of TacV- L should lie around residue 1004 and the terminus of the thumb domain should be in the vicinity of residue 1543. This contention holds upon the prediction that región III of TacV-L would include a full set of secondary structure elements necessary to complete the topology of the fold found in hepatitis C virus-RdRp. This is at variance with the model of Vieth, S. which would lack four and five a-helices at the N- and C-termini, respectively. Thus, in our model a more realistíc representation of the protein surface is achieved. This feature becomes of the utmost importance for reaching a valid interpretation of interaction phenomena involving this protein. This model will allow us the interpretation of experimental results on the interaction between TacV-L protein and its inhibitor, the virus-encoded Z-protein.This knowledge will be of vital importance for the design of antivirals directed to pathogenic arenaviruses.