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

TitleHigher expression of several interferon-stimulated genes in HIV-1-infected females after adjusting for the level of viral replication.
Publication TypeJournal Article
Year of Publication2013
AuthorsJ Chang J, Woods M, Lindsay RJ, Doyle EH, Griesbeck M, Chan ES, Robbins GK, Bosch RJ, Altfeld M
JournalJ Infect Dis
Volume208
Issue5
Pagination830-8
Date Published2013 Sep 1
ISSN1537-6613
KeywordsAdult, Cells, Cultured, Dendritic Cells, Female, Gene Expression Profiling, Gene Expression Regulation, HIV Infections, HIV-1, Humans, Interferon-alpha, Male, Middle Aged, T-Lymphocytes
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.

DOI10.1093/infdis/jit262
Alternate JournalJ. Infect. Dis.
PubMed ID23757341
PubMed Central IDPMC3733517
Grant ListAI25879 / AI / NIAID NIH HHS / United States
AI27659 / AI / NIAID NIH HHS / United States
AI27666 / AI / NIAID NIH HHS / United States
AI38855 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
AI68634 / AI / NIAID NIH HHS / United States
AI68636 / AI / NIAID NIH HHS / United States
R01 AI078784 / AI / NIAID NIH HHS / United States
U01 AI038855 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01 AI069412 / AI / NIAID NIH HHS / United States
UM1 AI069412 / AI / NIAID NIH HHS / United States