A Point Mutation in the Human Parainfluenza Virus Type 2 Nucleoprotein Leads to Two Separate Effects on Virus Replication

 Human parainfluenza virus type 2 (hPIV2) represents Paramyxovirus genomes strictly following the "rule of six," with each nucleoprotein subunit (NP) binding precisely six nucleotides. Within NP's RNA binding groove, among ten residues, only Q202 directly engages with a nucleotide base, exemplifying the stringent adherence to this genomic principle. NPQ202 mutation leads to two distinct outcomes: facilitating the viral polymerase in replicating defective bipartite promoter minigenomes when NPwt is inactive, while hindering the conventional rescue of rPIV2 carrying this mutation. The absence of rPIV2 NPQ202A initially impeded a comprehensive analysis of the latter phenotype. After extensive cocultivation of transfected cells, researchers successfully recovered an rPIV2 variant with the NPQ202A mutation, found viable due to an additional NP mutation (I35L). This investigation infers separate effects induced by the Q202 mutation, resulting in the observed phenotypes. Additionally, it suggests a plausible link between the challenge in rescuing the virus and the incapacity of transfected cells to assimilate viral nucleocapsids during virus budding. The study highlights a potential secondary role of helical nucleocapsids' (NC) 3' ends in Paramyxovirus genomes. These ends might interact specifically with virus-modified cell membranes, crucial for integrating viral NCs into budding virions, impacting the virus lifecycle.

(LA)