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J Infect Dis. 2013 Sep 1;208(5):830-8. doi: 10.1093/infdis/jit262. Epub 2013 Jun 10.

Higher expression of several interferon-stimulated genes in HIV-1-infected females after adjusting for the level of viral replication.

Author information

1
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Harvard Medical School, Cambridge, MA 02139, USA.

Abstract

BACKGROUND:

Clinical studies have shown faster disease progression and stronger immune activation in human immunodeficiency virus (HIV)-1-infected females when compared with males for the same level of HIV-1 replication. Here we determine whether the elevated levels of HIV-1-induced interferon-alpha (IFN-α) production observed in females are associated with higher interferon-stimulated gene (ISG) expression levels in T cells, hence suggesting type-I IFN as a mechanism for the higher HIV-1-associated immune activation observed.

METHODS:

T-cell and dendritic cell populations were isolated from treatment-naive chronically HIV-1-infected individuals enrolled in the Adult Clinical Trials Group 384 by fluorescence-activated cell sorting. The expression of 98 genes involved in Toll-like receptor and type I IFN signaling pathways were quantified using Nanostring technology.

RESULTS:

Several ISGs were significantly correlated with HIV-1 viral load and/or CD4(+) T-cell count. Higher expression levels of a subset of these ISGs were observed in cells derived from females as compared to males after adjusting for viral load and were correlated to higher levels of T-cell activation.

CONCLUSION:

These data show that higher IFN-α production is associated with higher ex vivo expression of several ISGs in females. This might contribute to higher levels of immune activation and the observed faster HIV-1 disease progression in females for a given level of viral replication.

KEYWORDS:

HIV-1; T cells; Toll-like receptors; dendritic cells; immune activation; innate immunity; pathogenesis; sex differences; type I Interferon

PMID:
23757341
PMCID:
PMC3733517
DOI:
10.1093/infdis/jit262
[Indexed for MEDLINE]
Free PMC Article

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