Although human immunodeficiency virus (HIV) is the etologic agent of AIDS, there is little doubt than other agents such as HCMV, which are also immunosuppressive may play some role in the development of AIDS. This may occur either through HCMV acting synergistically with in producing immunosuppression or by the two virus somehow enhancing the replication of each other. Preliminary data from our laboratory indicates that the virus capsid of HCMV contains a protein which interacts in vitro with human T lymphocytes causing cell fusion. Our hypothesis is that HIV initially immunossuppresses the immune response of patients, thus activating HCMV, which is already present as a latent infection in virtually 100% of those patients which will develop AIDS. Following activation HCMV further represses the immune response through interaction of a virion protein with T cells The goal of these proposed investigations will be to investigate interaction between the HCMV fushion protein and human T cells. These studies will be pursued as follows. An assays system for detection of the fusion protein will be developed. The protein will be isolated from HCMV virions and its isoelectric point and molecular weight determined. These parameters will be used to develop a purification system for the protein. Monoclonal and/or polyclonal antibody will be prepared and screened for its ability to block HCMV induced T cell fusion and virus replication. Antibody which reacts specifically with the fusion protein will be used to screen a lambda gtll library prepared from HCMV infected cell mRNA. The cDNA homologous to the mRNA coding for the fusion protein will be used to map the position of the gene on the virus chromosome ana analyze its expression during virus infection. The gene will be sequenced and from this information it will be expressed in a prokaryotic vector system.
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