When a DNA tumor virus infects a cell the outcome of the infection depends on the interaction of specific host and viral factors. These interactions ultimately determine the outcome of the infection (lytic, semipermissive, latent, persistent or transforming). The DNA tumor virus Simian Virus 40 exhibits a variety of host-viral interactions: lytic in African green monkey kidney (AGMK) cells, latent in rhesus monkey cells, semipermissive in human cells and abortive or transforming in mouse cells. Thus we have a well characterized virus and a variety of cells in which to study the molecular mechanisms of: 1) host-viral interactions; 2) host range; and 3) the factors which determine the course of a viral infection in a particular cell. We have approached this problem through the examination of specific small RNAs which bear homology with SV40 DNA. These include: 1) the SV40 associated small RNA (SAS-RNA), a 64 nucleotide RNA encoded by the virus and 2) SV40 homologous RNAs (SH-RNAs) some of which we know are of cellular origin. Based on our own data, and the evidence that cellular small RNAs are involved in regulatory processes, we believe that the presence or absence of particular small RNAs in a cell may affect host-viral interactions in such a way as to influence the ultimate outcome of a viral infection. To support this we have extensively characterized the SAS-RNA. In preliminary experiments, it appears that the SAS-RNA is required for normal expression of late viral proteins in primate cells which maintain SV40 in a latent state (rhesus cells); however this requirement for SAS-RNA is not observed in the normal tissue culture host cells (AGMK). This offers an ideal system in which we will characterize the molecular biology of different host-viral interactions. A complete study will involve experimentation with a number of primate and rodent cells. In addition, we will thoroughly characterize the SH-RNAs because our preliminary data also indicate that SH-RNAs are quite different between permissive and nonpermissive cells. These differences may determine permissivity. A third line of proposed research involves RNA processing. Our data shows that the SAS-RNA arises by processing from larger viral transcripts. Thus we will take advantage of this system for the isolation and characterization of a eucaryotic RNA processing enzyme(s).
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