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Journal of Virology, January 2008, p. 893-902, Vol. 82, No. 2
0022-538X/08/$08.00+0     doi:10.1128/JVI.01373-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 Vpu Protein Interacts with CD74 and Modulates Major Histocompatibility Complex Class II Presentation{triangledown}

Amjad Hussain,1 Clement Wesley,1 Mohammad Khalid,1 Ashutosh Chaudhry,2 and Shahid Jameel1*

International Centre for Genetic Engineering and Biotechnology, New Delhi, India,1 National Institute of Immunology, New Delhi, India2

Received 25 June 2007/ Accepted 15 October 2007

The human immunodeficiency virus type 1 (HIV-1) Vpu accessory protein is a transmembrane protein that down regulates CD4 expression and promotes the release of new virions. We screened a human leukocyte-specific yeast two-hybrid expression library to discover novel Vpu-interacting cellular proteins. The major histocompatibility complex class II (MHC II) invariant chain, also called Ii or CD74, was found to be one such protein. We show direct binding of Vpu and CD74 by using a yeast two-hybrid assay and coimmunoprecipitation from HIV-1-infected cells. The cytoplasmic region of Vpu was found to interact with the 30-amino-acid cytoplasmic tail of CD74. Human monocytic U937 cells infected with wild-type or Vpu-defective HIV-1 and transfected cells showed that Vpu down modulated the surface expression of mature MHC II molecules. The reduction in cell surface mature MHC II molecules correlated with decreased antigen presentation to T cells in culture. Thus, the Vpu protein also contributes to viral persistence by attenuating immune responses during HIV infection. This report further exemplifies the rich diversity and redundancy shown by HIV in immune evasion.

* Corresponding author. Mailing address: Virology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India. Phone: 91-11-26742357. Fax: 91-11-26742316. E-mail: shahid{at}icgeb.res.in

{triangledown} Published ahead of print on 24 October 2007.

Journal of Virology, January 2008, p. 893-902, Vol. 82, No. 2
0022-538X/08/$08.00+0     doi:10.1128/JVI.01373-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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  • Stratov, I., Chung, A., Kent, S. J. (2008). Robust NK Cell-Mediated Human Immunodeficiency Virus (HIV)-Specific Antibody-Dependent Responses in HIV-Infected Subjects. J. Virol. 82: 5450-5459 [Abstract] [Full Text]  


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