1st National Conference Human Retroviruses and Related Infections Washington, DC - December 12-16, 1993

Natl Conf Hum Retrovir Relat Infect 1993 Dec 12-16;1: (abstract no. 11)

Strebel K, Willey R
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 4/312, Bethesda, MD 20892

The HIV-1 vpu gene encodes an 81 amino acid integral membrane phosphoprotein which is expressed in significant amounts in HIV-infected cells but is absent from virions. We identified in the past two biological activities of Vpu: (i) enhancement of virion release from HIV-1 infected cells and (ii) degradation of CD4, the cell surface receptor for HIV, in the endoplasmic reticulum of cells.¹ The availability of an in vitro CD4 degradation assay allowed us to define important parameters for Vpu-dependent CD4 degradation. We found that truncation of part of the CD4 cytoplasmic domain abolished the sensitivity of Vpu to CD4 suggesting that sequences in the cytoplasmic domain of CD4 confer sensitivity to Vpu.² We now extended these studies to demonstrate that cytoplasmic sequences of CD4 are indeed sufficient to confer sensitivity to Vpu. Portions of the CD4 protein were introduced into CD8, which is insensitive to Vpu. We found that transfer of CD4 cytoplasmic sequences into CD8 resulted in Vpu- dependent degradation of the CD8/CD4 chimeric proteins. In contrast, transfer of other portions of CD4 into CD8 did not result in Vpu-dependent destabilization of the resulting chimeras. Therefore, sequences present in the cytoplasmic domain of CD4 are necessary and sufficient to confer sensitivity to Vpu.

¹Willey et al., “Human immunodeficiency virus type 1 Vpu protein induces rapid degradation of CD4”, J Virol. 1992 Dec;66(12):7193-200
²Chen et al., “Human immunodeficiency virus type 1 Vpu protein induces degradation of CD4 in vitro: the cytoplasmic domain of CD4 contributes to Vpu sensitivity”, J Virol. 1993 Jul;67(7):3877-84

Keywords: Acquired Immunodeficiency Syndrome, Animals, Antigens, CD4, Antigens, CD8, Base Sequence, Endoplasmic Reticulum, Genes, vpu, HIV Seropositivity, HIV-1, In Vitro, Virion, genetics, immunology

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1993-12-12
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