This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Liu, Q.
Right arrow Articles by Alter, G.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liu, Q.
Right arrow Articles by Alter, G.

 Previous Article  |  Next Article 

Journal of Virology, September 2009, p. 8705-8712, Vol. 83, No. 17
0022-538X/09/$08.00+0     doi:10.1128/JVI.02666-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Matrix Metalloprotease Inhibitors Restore Impaired NK Cell-Mediated Antibody-Dependent Cellular Cytotoxicity in Human Immunodeficiency Virus Type 1 Infection {triangledown}

Qingquan Liu,1,2 Yongtao Sun,2* Suzannah Rihn,1 Anne Nolting,1 Peter Nicholas Tsoukas,1 Stephanie Jost,1 Kristen Cohen,1 Bruce Walker,1,3 and Galit Alter1*

Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts,1 Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China,2 Howard Hughes Medical Institute, Chevy Chase, Maryland3

Received 28 December 2008/ Accepted 15 June 2009

Increasing evidence suggests that NK cells not only are critical in the initial host defense against pathogens but also may contribute to continued protection from human immunodeficiency virus type 1 (HIV-1) disease progression. NK cell cytolysis can be induced directly through diverse receptor families or can be induced indirectly through Fc receptors by antibodies mediating antibody-dependent cellular cytotoxicity (ADCC). ADCC has been implicated in both protection from simian immunodeficiency virus infection and slower progression of HIV-1 disease. ADCC activity declines with advancing infection, and yet the underlying mechanism for this dysfunction has not been defined, nor has it been determined whether the activity can be reconstituted. Here we demonstrate that NK cell-mediated ADCC is severely compromised in chronic HIV infection. The potency of ADCC function was directly correlated with baseline Fc{gamma}RIIIa receptor (CD16) expression on NK cells. CD16 expression was negatively influenced by elevated expression of a group of enzymes, the matrix metalloproteinases (MMPs), normally involved in tissue/receptor remodeling. Inhibition of MMPs resulted in increased CD16 expression and augmented ADCC activity in response to antibody-coated target cells. These data suggest that MMP inhibitors may improve NK cell-mediated ADCC, which may provide subjects with an opportunity to harness the cytolytic power of NK cells through naturally occurring nonneutralizing HIV-specific antibodies.

* Corresponding author. Mailing address for Yongtao Sun: Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University, 1st Xinsi Road, Baqiao District, Xi'an 710038, China. Phone: 86-29-84777652. Fax: 86-29-83537377. E-mail: yongtaos{at}hotmail.com. Mailing address for Galit Alter: Partners AIDS Research Center, Massachusetts General Hospitals, 149 13th Street, Boston, MA 02129. Phone: (617) 724-0546. Fax: (617) 726-5411. E-mail: galter{at}partners.org

{triangledown} Published ahead of print on 24 June 2009.

Journal of Virology, September 2009, p. 8705-8712, Vol. 83, No. 17
0022-538X/09/$08.00+0     doi:10.1128/JVI.02666-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»