Higher Expression of Several Interferon-Stimulated Genes in HIV-1-Infected Females After Adjusting for the Level of Viral Replication

• Published in: The Journal of infectious diseases 2013-09, Vol.208 (5), p.830-838
• Main Authors: Chang, J. Judy, Woods, Matt, Lindsay, Robert J., Doyle, Erin H., Griesbeck, Morgane, Chan, Ellen S., Robbins, Gregory K., Bosch, Ronald J., Altfeld, Marcus
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Cells, Cultured; Dendritic cells; Dendritic Cells - immunology; Disease progression; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Gene Expression Regulation; HIV; HIV 1; HIV Infections - immunology; HIV-1 - immunology; HIV/AIDS; Human immunodeficiency virus; Human immunodeficiency virus 1; Human viral diseases; Humans; Infections; Infectious diseases; Interferon-alpha - immunology; Major and Brief Reports; Male; Medical sciences; Messenger RNA; Microbiology; Middle Aged; Miscellaneous; Sex linked differences; T lymphocytes; T-Lymphocytes - immunology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral load; Virology; Women
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jit262

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.