HIV interferes with SOCS‐1 and ‐3 expression levels driving immune activation

HIV infection is characterized by sustained immune activation, which is reflected by activated T cells and, in particular, by increased levels of phosphorylated STAT proteins. Here, we hypothesized that T‐cell activation in HIV infection is partially due to the inability of SOCS‐1 and SOCS‐3 to cont...

Full description

Saved in:
Bibliographic Details
Published in:European journal of immunology 2011-04, Vol.41 (4), p.1058-1069
Main Authors: Miller, Regina C., Schlaepfer, Erika, Baenziger, Stefan, Crameri, Reto, Zeller, Sabine, Byland, Rahel, Audigé, Annette, Nadal, David, Speck, Roberto F.
Format: Article
Language:English
Subjects:
Adult
Antiretroviral drugs
Cells, Cultured
Drug therapy
Gene Expression Regulation
HIV
HIV Infections - immunology
HIV Infections - metabolism
Human immunodeficiency virus
Humans
Immune activation
Infections
JAK/STAT
Janus Kinases - metabolism
Lymphocytes
Middle Aged
RNA, Messenger - genetics
Signal Transduction
SOCS
STAT Transcription Factors - metabolism
Suppressor of Cytokine Signaling 1 Protein
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins - genetics
Suppressor of Cytokine Signaling Proteins - immunology
T-Lymphocytes - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:HIV infection is characterized by sustained immune activation, which is reflected by activated T cells and, in particular, by increased levels of phosphorylated STAT proteins. Here, we hypothesized that T‐cell activation in HIV infection is partially due to the inability of SOCS‐1 and SOCS‐3 to control the JAK/STAT pathway. We found higher levels of SOCS‐1/3 mRNA levels in CD4+ T cells of HIV‐infected patients than in healthy controls. However, SOCS protein levels were lower, explaining the lack of attenuation of the JAK/STAT pathway. Infection of CD4+ T cells alone did not activate STATs, while ex vivo infection of PBMC did, indicating that non‐T cells critical for shaping the immune response, e.g. DC were responsible for the STAT‐1 activation. Supernatants from ex vivo‐infected PBMC transferred to CD4+ T cells induced JAK/STAT activation, pointing to a central role of soluble factors. Notably, over‐expression of SOCS‐1/3 in CD4+ T cells prevented JAK/STAT activation. Thus, HIV infection interferes with SOCS‐1/3 expression driving immune activation. Sustained immune activation disrupts the lymphoid system and favors HIV replication since HIV preferentially infects activated cells. We speculate that regulating SOCS may be a potential way to counteract immune activation in HIV disease.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.201041198