A Point Mutation in the RNA-Binding Domain of Human Parainfluenza Virus Type 2 Nucleoprotein Elicits Abnormally Enhanced Polymerase Activity

Human parainfluenza virus type 2 (HPIV2) from the family paramyxoviridae contains six genes (NP, P/V, M, F, HN and L) which are firmly covered by the nucleoprotein (NP) forming a helical nucleocapsid. This nucleocapsid is the template for synthesis of viral RNA. Transcription and replication are the functions of Phosphoprotein (P) and large protein (L) which together form the viral RNA-dependent RNA polymerase (RdRp). This virus has several amino acids. For optimum replication to take place the RNA genome length must be a multiple of six nucleotides. This is a rule that is followed by all the paramyxoviruses and is known as the ‘rule of six’. In this study ten amino acids in NP that contacts RNA and are conserved in the HPIV2 and PIV5 viruses were examined for polymerase activity. They found out that when there is substitution mutation of HPIV2 Q202 to different amino acids, the polymerase activity increases but the affinity of RNA binding is not changed. This means genome replication is increased. Another interesting finding is that with the mutation, minigenomes without leader sequence and not multiple of six were used by the polymerase. However, this mutation does not affect the functions of NP such as signal editing and junctional recognition.

(BEC)