Obstruction of HIV-1 Particle Release by Interferon-α Occurs Before Viral Protease Processing and Is Independent of Envelope Glycoprotein

Abstract

The effect of human interferon-alpha (Hu-IFN-alpha) on the maturation process of the human immunodeficiency virus type 1 (HIV-1) has been studied using stable cell lines that produce nonenveloped particles. These cell lines secrete particles devoid of the viral envelope proteins gp120 and gp41. The CH-1 cells produce active viral protease that correctly processes its natural substrates, whereas the CH-1kww cell line expresses an enzymatically inactive viral protease, thus producing immature viral capsids. A block in the secretion of particles was observed in both cell lines when treated with 100-1000 U/ml Hu-IFN-alpha, as judged by measurements of encapsidated gag proteins. Electron microscopy shows that Hu-IFN-alpha-treated CH-1 cells are decorated with assembled immature particles at the cell surface. These results suggest that the observed block in particle release on Hu-IFN-alpha treatment is independent of viral envelope expression and occurs before capsid polyprotein processing. In addition, particles remaining attached to the cell fail to mature into structures with condensed cores. Viral gag proteins from IFN-treated and untreated CH-1 cells were analyzed by 2-D gel electrophoresis. Results suggest a change in posttranslational modifications of gag proteins, as IFN treatment allowed the detection of more basic forms of p55, p39, and p24. Further analysis of cellular or viral protein alterations induced by Hu-IFN-alpha treatment may identify the mechanism of action by which particle maturation is obstructed.

Effect of Type-I Interferon on Retroviruses

“…It has been reported that IFN-I may produce a change in post-translation modifications of Gag proteins, as more basic forms of p55, p39 and p24 were detected in HIV-infected stable cell lines, which inhibit capsid polyprotein processing. In addition, particles remaining attached to the cell failed to mature into structures with condensed cores [8]. Other studies suggest that IFN-α blocks HIV-I release mediated by the ubiquitin ligase, ISG-15, one the IFN-induced proteins of the ubiquitin-like pathway.…”

Role of Placental Cytokines in Transcriptional Modulation of HIV Type 1 in the Isolated Villous Trophoblast

“…Type I IFNs (a and b) suppress HIV replication at the levels of transcription initiation, 41 mRNA stability, 42 translation, 43 assembly and release of virions, 44,45 and reverse transcription. 46 The response to IFN also depends on the stage of infection as well as the cell type.…”

IFN-Dependent and -Independent Reduction in West Nile Virus Infectivity in Human Dermal Fibroblasts

“…In studies utilizing several different viruses, infected cells treated with IFN produced viral particles with lower infectivity compared to untreated control cells [ 36 , 37 , 38 , 39 , 40 , 41 ]. To assess whether IFN plays a similar role in reducing WNV infectivity, we examined the effect of IFN-β neutralizing antibodies on the particle to PFU ratios of WNV-NY and WNV-AUS60.…”