The impact of mutations affecting highly conserved amino acids in the simian immunodeficiency virus nucleocapsid protein on virion assembly, genomic RNA packaging and viral infectivity

The nucleocapsid (NC) domain of the retroviral Gag polyproteins mediates the incorporation of the viral genomic RNA into virions. Although SIV is widely used as a model for human immunodeficiency virus type 1 (HIV-1) infections, the SIV NC has been the subject of few studies which have provided discrepant data on the relative contribution of the two NC zinc finger motifs to genomic RNA encapsidation. Here, we demonstrate that mu-tations affecting the first cysteine in the distal zinc finger motif (C33S) or the N-terminal NC basic domain (R7A/ K8A) drastically impair virion assembly and viral RNA binding. By contrast, amino acid substitutions targeting the first cysteine of the proximal zinc finger (C12S) or the basic region connecting both zinc fingers (R29A/R30A) allow substantial particle production and genomic RNA encapsidation. Our results help define the relative contribution of the SIV NC zinc finger motifs and basic regions to the NC biological properties.

Automated summary

Mutations C33S and R7A/K8A impair virion assembly and viral RNA binding, while mutations C12S and R29A/R30A allow substantial particle production and genomic RNA encapsidation. These findings help define the relative contribution of the SIV NC zinc finger motifs and basic regions to the NC biological properties.