title: HIV interferes with SOCS-1 and -3 expression levels driving immune activation.
abstract: 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.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Regina C
authors.initials: RC
authors.lastname: Miller
authors.forename: Erika
authors.initials: E
authors.lastname: Schlaepfer
authors.forename: Stefan
authors.initials: S
authors.lastname: Baenziger
authors.forename: Reto
authors.initials: R
authors.lastname: Crameri
authors.forename: Sabine
authors.initials: S
authors.lastname: Zeller
authors.forename: Rahel
authors.initials: R
authors.lastname: Byland
authors.forename: Annette
authors.initials: A
authors.lastname: Audigé
authors.forename: David
authors.initials: D
authors.lastname: Nadal
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Speck
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D012333:RNA, Messenger; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; D050791:STAT Transcription Factors; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D053612:Janus Kinases