ANALYSIS OF CELLULAR FACTORS AFFECTING RETROVIRUS INFECTION AND GROWTH

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Retrovirus replication has been shown to require both viral and cellular components, and cellular factors or functions are known to restrict retrovirus infection and growth. This occurs most frequently at the level of virus attachment and penetration, but other post-penetration effects have also been described. Understanding cellular mechanisms of viral control may be useful in our attempts to develop antiviral agents which affect human retroviruses, such as HIV and HTLVI. The goal of this project is to characterize the role of cellular factors in the growth and restriction of retrovirus infection. Previously, we had reported that RD114 restriction in feline cells does not occur at the level of the proviral LTR, since reporter genes linked to the LTR function efficiently in both restrictive and permissive cells. We have extended our analysis of the mechanism of restriction of growth of RD114 virus in feline fibroblasts, and can show that the expression of endogenous RD114-related mRNAs correlates with the restricted phenotype. Additionally, restricted cells express RD114 glycoprotein molecules of approximately gp85 kD instead of the expected gp7O following RD114 transfection or infection. Interaction between the RD114 receptor and the modified gp7O molecule is probably responsible for the restricted ability of RD114 virus to spread in feline fibroblasts. We have also studied the growth of feline immunodeficiency virus (FIV) in the cat brain-derived cell line, G355, and have shown that certain strains of the virus are fusigenic and cytotoxic for these cells. Interference analysis indicates that FIV utilizes a receptor on G355 cells which is different from the ones used by feline endogenous and exogenous viruses. Cell fusion is enhanced by the presence of replicating C-type viruses and is further enhanced in cells transformed by the mos-containing Mo-MuSV. The fusion of MSV-transformed G355 cells provides an easily quantifiable biological assay for virus infectivity in an adherent cell line.