Date of Graduation

1997

Document Type

Thesis

Abstract

Retroviruses can packaged two copies of their RNA genome into a single virion. If two different RNAs are co-packaged together, both strands can be used as templates to generate a single DNA provirus during reverse transcription. In this dissertation, we studied mechanisms that may allow genetically distinct retroviruses to exchange genetic information. First, we examined whether minus-strand DNA transfer could occur between R regions with diminished sequence homology. It was found the only very short stretches of homology were necessary and that minus-strand DNA transfer was not limited to the R region. Thus, it is possible that viruses with different R regions may interact through this mechanism. A second question that was addressed was whether RNAs containing the encapsidation sequences of two genetically distinct retroviruses could co-package into the same virion. Such an event is critical for any exchange of genetic material to occur during reverse transcription. In our experimental system, we were able to observe proviruses that contained sequences from the different RNAs. This indicates that RNA from different retroviruses can be co-packaged and exchange genetic information. We concluded from these experiments that it is possible for different retroviral species to interact, which could result in the generation of a recombinant retrovirus with a significantly altered phenotype than either of its parents. This may have far-reaching implications for retroviral evolution and pathogenesis. Finally, in a third experiment we observed that inserting sequences into the 3{dollar}\\sp\\prime{dollar} untranslated region of the spleen necrosis virus disrupted replication. We demonstrated that this defect was due to an impairment in env expression that is likely to occur at a post RNA processing step. These results suggest the disruption of a novel cis-acting element in SNV.

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