The entire SU subunit is required for the incorporation of the HIV-1 envelope glycoprotein complex into virions.

A modified envelope glycoprotein of the human immunodeficiency virus type 1 (HIV-1) containing an intact TM subunit, but lacking most of the gp120/SU subunit was transported and expressed on the membrane of COS-1 cells. However, this deleted glycoprotein, failed to be incorporated into the budding viral particles. This suggested that a particular domain(s) of the gp120/SU glycoprotein subunit could be required for envelope incorporation. To explore this possibilty, we constructed envelope genes containing specific domains of the SU protein in-frame with the TM subunit. Transient expression studies indicated that any envelope primary translation product containing one or more of the gp 20/SU variable domains and the entire gp41/TM protein was transported and stably expressed on the cell surface. However, efficient proteolytic processing of these Env precursors into gp41, was not observed. The addition of more than 90% of the SU sequences into the deleted Env product, including the five variable domains, were insufficient to promote incorporation of this glycoprotein precursor into virions. These results suggest that the native conformation of the SU subunit is an essential requirement for the efficient incorporation of the Env complex into virons. The C1 domain of the SU glycoprotein subunit constitutes an important determinant that makes the envelope complex assembly-competent, but, by itself, it is not sufficient to drive this process.