Inhibition of cellular glycoprotein incorporation into human immunodeficiency virus-like particles by coexpression of additional cellular interaction partner.

We examined the concepts of whether cellular surface glycoprotein overexpressed in heterologous cells can be efficiently incorporated into lentiviral particles and whether incorporation is blocked when a natural interaction partner is coexpressed. Human CD4 and a truncated version lacking the cytoplasmic C terminus, expressed in 293T cells, were efficiently incorporated into Env-defective human immunodeficiency virus type 1 virus-like particles. However, on coexpression of p56(lck), the natural binding partner of the CD4 C-terminal domain in T lymphocytes, incorporation of the wild-type CD4 was completely abolished, whereas incorporation of the C-terminally truncated mutant remained unaffected. Confocal microscopy and detergent solubility assays did not reveal any significant difference in the distribution of wild-type CD4 at the plasma membrane in the presence or absence of p56(lck). These results give some insight into the processes governing protein incorporation into the lipid bilayer of lentiviruses. Copyright 1998 Academic Press.