Identification of a transfer of viral core protein to cellular ribosomes during the early stages of alphavirus infection.

Sindbis virus containing [35S]methionine-labeled structural proteins was allowed to be taken up by primary chick embryo fibroblasts, and the fate of the core protein was studied. The experiments show that core protein of incoming viral particles is transferred to the large subunit of cellular ribosomes during the initial steps of virus infection. A similar transfer occurs in vitro if cores isolated from SIN virus particles are incubated in the postmitochondrial cytoplasmic fraction of cell lysates. In vivo transfer also occurs if the protein synthesis-inhibiting drugs puromycin or cycloheximide are present during virus uptake, whereas in the presence of chloroquine, which inhibits the release of viral cores into the cytoplasm, which is necessary for productive infection, a transfer of core protein to ribosomes cannot be observed. The latter result indicates that the transfer probably is part of the reactions leading to the release of viral genomic RNA into the cellular cytoplasm during the early stages of productive infection, and presumably does not reflect side reactions. It has been shown earlier that newly synthesized alphavirus core protein binds to the large ribosomal subunit prior to the assembly of viral core particles in infected cells [I. Ulmanen, H. Sonderlund, and L. Kääriäinen (1979) Virology 99, 265-276]. These data lead to the suggestion that the disassembly and assembly of alphavirus cores might be regulated by a process which could be called receptor-mediated core disassembly, in which acceptors exist for the protein components of viral nucleoproteins in uninfected cells which early in infection bind these proteins and thereby lead to disassembly of these complexes, and which later on have to be saturated with newly synthesized protein before efficient assembly of nucleoproteins can occur, and that the large ribosomal subunit functions as such a receptor during alphavirus replication.