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.

Autographa californica nuclear polyhedrosis virus-specific RNA synthesis in isolated nuclei of Spodoptera frugiperda cells in culture was monitored at different times postinfection. Up to 8 h postinfection viral RNA synthesis remained sensitive to 5 ,ug of a-amanitin per ml. During the course of infection this sensitivity decreased, and at 24 h postinfection RNA synthesis was completely resistant to a-amanitin. DEAE-Sephadex profiles of RNA polymerase isolated at 24 h postinfection showed a new, chromatographically distinct, a-amanitinresistant form whose kinetics and response to divalent cations differed from those of the host RNA polymerases. The possibility that this enzyme may be responsible for viral late transcription is discussed.

Background. Clinical studies have shown faster disease progression and stronger immune activation in HIV-1-infected females as compared to males for the same level of HIV-1 replication. This study assesses whether the elevated levels of HIV-1-induced IFN-α production observed in females were associated with higher interferon-stimulated gene expression levels in T cells, and hence suggesting type-I-IFN as a mechanism for the higher HIV-1-associated immune activation observed. Methods. Fluorescence activated cell sorting was used to isolate T cells and dendritic cells from PBMCs of treatment-naïve chronically HIV-1-infected individuals enrolled in ACTG 384. The expression of 98 genes involved in toll-like receptor and type-I-IFN signaling pathways were quantified using Nanostring technology on sorted cell populations. Results. Several interferon-stimulated genes were significantly correlated with HIV-1 viral load and/or CD4+ T cell count. Higher expression levels of a subset of these interferon-stimulated genes were observed in cells derived from females 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 and resulting higher ex vivo expression of several interferon-stimulated genes in females can contribute to higher levels of immune activation, and subsequently the observed faster HIV-1 disease progression in females for a given level of viral replication.