A selective defect of IFN-gamma- but not of IFN-alpha-induced JAK/STAT pathway in a subset of U937 clones prevents the antiretroviral effect of IFN-gamma against HIV-1

Citation
C. Bovolenta et al., A selective defect of IFN-gamma- but not of IFN-alpha-induced JAK/STAT pathway in a subset of U937 clones prevents the antiretroviral effect of IFN-gamma against HIV-1, J IMMUNOL, 162(1), 1999, pp. 323-330
Citations number
47
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
00221767 → ACNP
Volume
162
Issue
1
Year of publication
1999
Pages
323 - 330
Database
ISI
SICI code
0022-1767(19990101)162:1<323:ASDOIB>2.0.ZU;2-T
Abstract
IFN-gamma induces transcription of several IFN-stimulated genes (ISGs), Rec ently, the IFN-gamma-dependent Janus kinase (JAK)/STAT pathway has been sho wn to mediate the activation of some ISGs, by the sequential phosphorylatio n of two JAK kinases (JAK1 and JAK2) and of STAT1, Given that the JAK/STAT is the major, but not the only pathway linked to the IFN-gamma R, aim of ou r work was to investigate the signal-transduction pathway(s) by which IFN-g amma exerts its effects on acute replication of HIV in monocytic cells, To this end, we utilized clones previously derived from the U937 promonocytic cell line, differing for their efficient (plus clones) or inefficient (minu s clones) abilities of supporting HIV replication. Unlike IFN-alpha, IFN-ga mma did not inhibit HIV replication in plus clones, whereas virus productio n in minus cells was efficiently inhibited by both types of IFN, Plus clone s generated a JAK/STAT signal-transduction pathway in response to IFN-alpha , but not IFN-gamma, In contrast, minus clones responded to either cytokine s. The functional defect of plus clones in response to IFN-gamma was correl ated to a selective defect of IFN-gamma R2, but not IFN-gamma R1, membrane expression. Surprisingly enough, IFN-gamma stimulation of plus clones induc ed IFN-stimulated gene factor 3 (ISGF3 gamma), These results strongly suppo rt the hypothesis that the JAK/STAT pathway is responsible for the antiretr oviral effect of IFN-gamma, and further provide evidence for a potential se cond pathway triggered by IFN-gamma in the absence of IFN-gamma R2 chain ce ll surface expression and involving ISGF3 gamma.