Human immunodeficiency virus type 1 Vpu modifies viral cytopathic effect through augmented virus release

We characterized two human immunodeficiency virus type 1 (HIV-1) strains, HIV(MCK) and HIV₂₁₃, which have different cytopathic effects in infected cells. HIV₂₁₃ was highly cytopathic, whereas HIV(MCK) was not. Biological analyses of chimeric viruses from the cloned infectious DNAs of HIV(MCK) and HIV₂₁₃ showed that the Vpu region was responsible for the differing cytopathicity of these viruses. Although HIV(MCK) expressed Vpu protein, HIV₂₁₃ did not because of a mutation at the start codon for Vpu. The amounts of envelope glycoprotein and virus particles associated with the cell surface were significantly increased on cells infected with Vpu-deficient viruses compared with Vpu-positive viruses. These data suggest that the highly cytopathic effects of HIV₂₁₃ (Vpu-deficient) are due to an accumulation of envelope glycoprotein at the infected-cell surface, which would be caused by the retention of progeny virions in the absence of Vpu-facilitated virion release.