FIG. 9.

Model of the initiation of positive-strand RNA synthesis. Negative-strand template RNA, usually found as part of the double-stranded RF, is depicted in green as single stranded for simplicity. Nascent positive-strand RNA (B) is depicted by a black dashed arrow. (A) Prior to positive-strand RNA synthesis, the 5′ and 3′ termini associate with known (hnRNP C) and unknown (host) cellular proteins, in addition to viral proteins 3C/3CD and 2C. Binding of hnRNP C, possibly in conjunction with other viral/cellular proteins, allows interaction of 3C/3CD with the negative-strand RNA termini. (B) These interactions may allow contact of the 5′ and 3′ ends of the RF (indicated by the double-headed arrow), possibly facilitating initiation of positive-strand RNA synthesis by the RNA-dependent RNA polymerase (3D^pol). The activity of hnRNP C in the virus RNA replication cycle may be a rate-limiting step during the initial stages of poliovirus infection, where the hnRNP C cytoplasmic concentration is low. At later times postinfection, hnRNP C distribution shifts to the cytoplasm of the infected cell. VPg, the genome-linked protein of poliovirus; pUpU, the first two nucleotides of poliovirus genomic RNA.