Analysis of the human immunodeficiency virus type 1 M group Vpu domains involved in antagonizing tetherin.

Abstract

Zoonosis of chimpanzee simian immunodeficiency virus cpz to humans has given rise to both pandemic (M) and non-pandemic (O, N and P) groups of human immunodeficiency virus type-1 (HIV). These lentiviruses encode accessory proteins, including Vpu, which has been shown to reduce CD4 levels on the cell surface, as well as increase virion release from the cell by antagonizing tetherin (CD317, BST2). Here, we confirm that O group Vpus (Ca9 and BCF06) are unable to counteract tetherin or downregulate the protein from the cell surface, although they are still able to reduce cell-surface CD4 levels. We hypothesize that this inability to antagonize tetherin may have contributed to O group viruses failing to achieve pandemic levels of human-to-human transmission. Characterization of chimeric O/M group Vpus and Vpu mutants demonstrate that the Vpu-tetherin interaction is complex, involving several domains. We identify specific residues within the transmembrane proximal region that, along with the transmembrane domain, are crucial for tetherin counteraction and enhanced virion release. We have also shown that the critical domains are responsible for the localization of M group Vpu to the trans-Golgi network, where it relocalizes tetherin to counteract its function. This work sheds light on the acquisition of anti-tetherin activity and the molecular details of pandemic HIV infection in humans.

• Authors: Sarah J Petit, Caroline Blondeau, Greg J Towers
• Journal: The Journal of general virology (J Gen Virol) Vol. 92 Issue Pt 12 Pg. 2937-2948 (Dec 2011) ISSN: 1465-2099 [Electronic] England
• PMID: 21900423 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• BST2 protein, human
• GPI-Linked Proteins
• Human Immunodeficiency Virus Proteins
• Viral Regulatory and Accessory Proteins
• vpu protein, Human immunodeficiency virus 1

Topics

• Amino Acid Sequence
• Antigens, CD (metabolism)
• Blotting, Western
• CD4-Positive T-Lymphocytes (metabolism)
• Cloning, Molecular
• Down-Regulation
• Fluorescent Antibody Technique
• GPI-Linked Proteins (metabolism)
• Gene Expression Regulation, Viral
• HIV Infections (virology)
• HIV-1 (genetics, metabolism)
• Human Immunodeficiency Virus Proteins (genetics, metabolism)
• Humans
• Molecular Sequence Data
• Protein Interaction Domains and Motifs
• Viral Regulatory and Accessory Proteins (genetics, metabolism)