Influence of human immunodeficiency virus type 1 envelope glycoprotein YXXL endocytosis/polarization signal on viral...

A tyrosine-based targeting signal in the intracytoplasmic domain of human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein is required for basolateral targeting of viral budding in polarized epithelial cells, concentration of viral assembly at one pole of infected lymphocytes, and rapid endocytosis of the glycoprotein from the plasma membrane. In HIV-1, the process of viral assembly and budding is complex and involves the participation of viral accessory proteins.

In this study, we examined whether the functions of the Nef, Vif, and Vpu proteins can influence or be influenced by the presence of envelope targeting signal in epithelial cells or lymphocytes. A series of proviral DNAs combining a mutation that inactivates the targeting signal with independent mutations in the three accessory proteins was constructed for this purpose.

It was found that none of these three accessory proteins affected the basolateral release of the virus in polarized MDCK cells. Reciprocally, a mutation abolishing targeting of the viral envelope glycoprotein did not affect the phenotype conferred by the accessory proteins. Interestingly, the mutation abolishing targeting increased viral infectivity only in the presence of the Vpu protein. This phenotype was found to be associated with the release-enhancing function of Vpu and with an increased incorporation of viral envelope glycoprotein in virions.

These data clearly show that accessory protein functions, and more specifically Vpu modulation of viral infectivity, can be affected by variations in the viral envelope glycoprotein.