|
|
Blood, 28 May 2009, Vol. 113, No. 22, pp. 5497-5505.
Prepublished online as a Blood First Edition Paper on March 19, 2009; DOI 10.1182/blood-2008-11-190231.
 Previous Article | Next Article 
Submitted November 18, 2008
Accepted March 12, 2009
Desensitization to type-I interferon in HIV-1 infection correlates with markers of immune activation and disease progression
Gareth A.D. Hardy, Scott F. Sieg, Benigno Rodriguez, Wei Jiang, Robert Asaad, Michael M. Lederman, and Clifford V. Harding*
Department of Pathology, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, OH, United States
Division of Infectious Diseases, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, OH, United States
Center for AIDS Research, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, OH, United States
* Corresponding author; email: cvh3{at}cwru.edu.
Type I interferon (IFN / ) plays a complex role in HIV-1 infection and has been proposed alternately to have roles in either disease protection or progression. Although IFN/ plays crucial roles in regulating monocytes and dendritic cells, responsiveness of these cells to IFN/ in HIV-1 infection is poorly understood. We report significant defects in IFN/ receptor (IFN/R) expression, IFN signaling and IFN-induced gene expression in monocytes from HIV-1-infected subjects. IFN/R expression correlated directly with CD4+ T cell count and inversely with HIV-1 RNA level and expression of CD38 by memory (CD45RO+) CD8+ T cells, a measure of pathological immune activation in HIV-1 infection associated with disease progression. In addition, monocytes from HIV-1-infected persons showed diminished responses to IFN, including decreased induction of phosphorylated STAT1 and the classical interferon-stimulated genes MxA and OAS. These IFN responses were decreased regardless of IFN/R expression, suggesting that regulation of intracellular signaling may contribute to unresponsiveness to IFN/ in HIV-1 disease. Defective monocyte responses to IFN/ may play an important role in the pathogenesis of HIV-1 infection, and decreased IFN/R expression may serve as a novel marker of disease progression.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. J. Conry, K. A. Milkovich, N. L. Yonkers, B. Rodriguez, H. B. Bernstein, R. Asaad, F. P. Heinzel, M. Tary-Lehmann, M. M. Lederman, and D. D. Anthony
Impaired Plasmacytoid Dendritic Cell (PDC)-NK Cell Activity in Viremic Human Immunodeficiency Virus Infection Attributable to Impairments in both PDC and NK Cell Function
J. Virol.,
November 1, 2009;
83(21):
11175 - 11187.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
