The goal of the proposed research is to identify and characterize the features of human immunodeficiency virus type 1 (HIV-1) that are responsible for the efficient and specific incorporation of viral RNA into HIV-1 particles. The elucidation of the mechanism of encapsidation and dimerization is an intrinsically important process for HIV-1 nucleic acid replication and virus propagation. These studies will focus on three general problems. First, we will elucidate the nature of the cis-acting encapsidation signal(s) on the viral RNA that function in RNA packaging. Our preliminary data support the hypothesis that there is a cis-acting encapsidation signal near the 5' end of the genome comprised of similar secondary structure in both HIV-1 and simian immunodeficiency virus. It is likely that this signal functions in conjunction with additional cis-actin sequences located downstream of the splice donor. Second, we will investigate the components of the Gag precursor protein which function as specificity factors for recognition and encapsidation of viral RNA. Our preliminary data indicate that the segment of the gag gene encoding the matrix protein serves as such a specificity factor. Finally, we will investigate the nature of the interaction between the two RNAs that comprise the dimeric RNA of the virion and determine the relationship between encapsidation and dimer formation. The association between the two RNAs of the virus, and of the viral RNAs with the virus core are almost certain to be required for accurate reverse transcription in vivo. An understanding of both the encapsidation process and the relationship between the two genomic RNAs will enhance our view of the overall process of nucleic acid replication. In addition, examination of encapsidation may reveal novel targets to abrogate retrovirus replication and suggest ways to increase the replication proficiency of HIV-1 vectors.
