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Journal of Virology, April 2007, p. 3354-3360, Vol. 81, No. 7
0022-538X/07/$08.00+0     doi:10.1128/JVI.02320-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Inhibition of Human Immunodeficiency Virus Type 1 Infection of Human CD4+ T Cells by Microbial HSP70 and the Peptide Epitope 407-426{triangledown}

Kaboutar Babaahmady,1 Wulf Oehlmann,2 Mahavir Singh,2 and Thomas Lehner1*

Mucosal Immunology Unit, King's College London at Guy's Hospital, London, United Kingdom,1 Lionex Diagnostics and Therapeutics, Braunschweig, Germany2

Received 19 October 2006/ Accepted 10 January 2007

Human immunodeficiency virus type 1 (HIV-1) virions contain heat shock proteins (HSP), but these proteins have received limited attention. The objectives of this study were to establish if the microbial 70-kDa HSP exerts an inhibitory effect on the HIV-1 infection of human CD4+ T cells, to identify an inhibitory peptide epitope within the sequence of HSP70, and to evaluate the kinetic features of any inhibitory activity. The results of these studies suggest that microbial HSP70 exerts dose-dependent inhibition on CCR5 (R5) strains of clades B, C, and D of HIV-1 infecting human CD4+ T cells. The site of the HIV-1-inhibitory function was identified within the C-terminal peptide binding domain of HSP70, and the function is expressed by the peptide epitope comprising amino acids 407 to 426. The mechanism of inhibition of HIV-1 infectivity by HSP70 is blocking of the CCR5 coreceptors directly and indirectly by inducing CC chemokines and APOBEC3G. The inhibitory effect of HSP70, its C-terminal fragment, or peptide 407-426 may make HSP70 useful as a microbicidal agent. A potentiating noncognate inhibition of HIV-1 infectivity by combined treatment with HSP70 and monoclonal or polyclonal antibody to CCR5 was demonstrated. This novel strategy may be utilized in therapeutic immunization against HIV-1 infection.

* Corresponding author. Mailing address: Guy's Hospital, Guy's Tower Floor 28, St. Thomas' Street, London SE1 9RT, England. Phone: 44 207 188 3072. Fax: 44 207 188 4375. E-mail: Thomas.lehner{at}kcl.ac.uk.

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

Journal of Virology, April 2007, p. 3354-3360, Vol. 81, No. 7
0022-538X/07/$08.00+0     doi:10.1128/JVI.02320-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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