POSSIBLE ROLES OF NUCLEOCAPSID PROTEIN OF MOMULV IN THE SPECIFICITY OF PROVIRAL DNA-SYNTHESIS AND IN THE GENETIC-VARIABILITY OF THE VIRUS

Retroviral nucleocapsid (NC) protein, in addition to its structural ro les in the virion core, is involved in the early and late phases of th e viral replication cycle. To further characterise the role of NC prot ein of MoMuLV (NCp10) in the replication of the viral genome, the infl uence of NCp10 on self-primed versus primer-specific reverse transcrip tion has been analysed in vitro. The results show that NCp10 can enhan ce the specificity of proviral DNA synthesis by inhibiting self-primed cDNA synthesis while promoting primer-specific DNA synthesis within a ctive NCp10-RNA nucleoprotein complexes. Retroviruses are known to sho w a high degree of variability and this prompted us to examine the pos sible implication of NCp10 in the genetic variability of MoMuLV. The a bility of reverse transcriptase (RT) to extend different mutated prime rs using an RNA or a DNA template has been investigated in the presenc e or in the absence of NCp10. NCp10 was found to have different effect s on RT depending on the nature of the template: an enhancement at the elongation level of mutated primers using RNA as template versus a sl ight inhibition using DNA as template. These observations suggest that NCp10 could be implicated in the genetic variability of MoMuLV by all owing nucleotide misincorporation principally during minus strand DNA synthesis. (C) 1998 Academic Press.