TY - JOUR
T1 - Innate immune dysfunction in HIV infection
T2 - Effect of HIV envelope-NK cell interactions
AU - Kottilil, Shyam
AU - Shin, Kyungmin
AU - Jackson, Julia O.
AU - Reitano, Kristin N.
AU - O'Shea, Marie Angeline
AU - Yang, Jun
AU - Hallahan, Claire W.
AU - Lempicki, Richard
AU - Arthos, James
AU - Fauci, Anthony S.
PY - 2006/1/15
Y1 - 2006/1/15
N2 - We have previously described a number of NK cell dysfunctions in HIV-viremic individuals. In the present study, we performed DNA microarray analysis followed by phenotypic and functional characterization in an effort to investigate which HIV envelope glycoproteins (gp120) affect the physiologic functions of NK cells. Upon treatment of NK cells with HIV gp120, DNA microarray analyses indicated up-regulation of several categories of genes that are associated with apoptosis, suppression of both cellular proliferation and survival, as well as down-regulation of genes that play a vital role in cell proliferation, innate immune defense mechanism, and cell survival. Both subtypes of gp120 suppressed NK cell cytotoxkity, proliferation, and the ability to secrete IFN-γ. NK cells exposed to X4-subtype HIV gp120 showed a significant decrease in the levels of CC chemokines, while exposure to R5-sobtype HIV gp120 had minimal effect. Extended exposure to HIV gp120 resulted in apoptosis of NK cells, further validating the microarray data. Our data demonstrate that exposure of NK cells to HIV envelope proteins results in profound cellular abnormalities at the level of gene expression as well as generic cell functions. These findings are likely to be a consequence of a direct HIV gp120-mediated effect on NK cells. Identification of specific surface receptors on NK cells that interact with HIV envelope proteins might explain how HIV is capable of circumventing innate immune defense mechanisms and establishing infection in susceptible individuals.
AB - We have previously described a number of NK cell dysfunctions in HIV-viremic individuals. In the present study, we performed DNA microarray analysis followed by phenotypic and functional characterization in an effort to investigate which HIV envelope glycoproteins (gp120) affect the physiologic functions of NK cells. Upon treatment of NK cells with HIV gp120, DNA microarray analyses indicated up-regulation of several categories of genes that are associated with apoptosis, suppression of both cellular proliferation and survival, as well as down-regulation of genes that play a vital role in cell proliferation, innate immune defense mechanism, and cell survival. Both subtypes of gp120 suppressed NK cell cytotoxkity, proliferation, and the ability to secrete IFN-γ. NK cells exposed to X4-subtype HIV gp120 showed a significant decrease in the levels of CC chemokines, while exposure to R5-sobtype HIV gp120 had minimal effect. Extended exposure to HIV gp120 resulted in apoptosis of NK cells, further validating the microarray data. Our data demonstrate that exposure of NK cells to HIV envelope proteins results in profound cellular abnormalities at the level of gene expression as well as generic cell functions. These findings are likely to be a consequence of a direct HIV gp120-mediated effect on NK cells. Identification of specific surface receptors on NK cells that interact with HIV envelope proteins might explain how HIV is capable of circumventing innate immune defense mechanisms and establishing infection in susceptible individuals.
UR - http://www.scopus.com/inward/record.url?scp=30744446711&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=30744446711&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.176.2.1107
DO - 10.4049/jimmunol.176.2.1107
M3 - Article
C2 - 16393999
AN - SCOPUS:30744446711
SN - 0022-1767
VL - 176
SP - 1107
EP - 1114
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -