Positive-sense ssRNA viruses have genetic material that can function both as a genome and as messenger RNA; it can be directly translated into protein in the host cell by host ribosomes. The first proteins to be expressed after infection serve genome replication functions; they recruit the positive-strand viral genome to
viral replication complexes (VRCs) formed in association with intracellular membranes. VRCs contain proteins of both viral and host cell origin, and may be associated with the membranes of a variety of organelles, often the rough endoplasmic reticulum, but also including membranes derived from mitochondria, vacuoles, the Golgi apparatus, chloroplasts, peroxisomes, plasma membranes, autophagosomal membranes, and novel cytoplasmic compartments. The replication of the positive-sense ssRNA genome proceeds through double-stranded RNA intermediates, and the purpose of replication in these membranous invaginations may be the avoidance of cellular response to the presence of dsRNA. In many cases subgenomic RNAs are also created during replication. After infection, the entirety of the host cell's translation machinery may be diverted to the production of viral proteins as a result of the very high affinity for ribosomes of the viral genome's internal ribosome entry site (IRES) elements; in some viruses, such as poliovirus and rhinoviruses, normal protein synthesis is further disrupted by viral proteases degrading components required to initiate translation of cellular mRNA.
All positive-sense ssRNA virus genomes encode RNA-dependent RNA polymerase (RdRP), a viral protein that synthesizes RNA from an RNA template. Host cell proteins recruited by positive-sense ssRNA viruses during replication include RNA-binding proteins, chaperone proteins, and membrane remodeling and lipid synthesis proteins, which collectively participate in exploiting the cell's secretory pathway for viral replication.