Anti-HIV state but not apoptosis depends on IFN signature in CD4+ T cells

Audigé, Annette; Urosevic, Mirjana; Schlaepfer, Erika; Walker, Russell; Powell, Doug; Hallenberger, Sabine; Joller, Helen; Simon, Hans-Uwe; Dummer, Reinhard; Speck, Roberto F (2006). Anti-HIV state but not apoptosis depends on IFN signature in CD4+ T cells. Journal of immunology, 177(9), pp. 6227-37. Bethesda, Md.: American Association of Immunologists

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To gain insights into the molecular mechanisms underlying early host responses to HIV in the CD4(+) T cell target population, we examined gene expression in CD4(+) T cells isolated 24 h after ex vivo HIV infection of lymphocyte aggregate cultures derived from human tonsils. Gene profiling showed a distinct up-regulation of genes related to immune response and response to virus, notably of IFN-stimulated genes (ISGs), irrespective of the coreceptor tropism of the virus. This mostly IFN-alpha-dependent gene signature suggested the involvement of plasmacytoid dendritic cells, a principal component of the antiviral immune response. Indeed, depletion of plasmacytoid dendritic cells before HIV inoculation abrogated transcriptional up-regulation of several ISGs and resulted in increased levels of HIV replication. Treatment with a blocking anti-IFN-alphaR Ab yielded increased HIV replication; conversely, HIV replication was decreased in pDC-depleted cultures treated with IFN-alpha. Among up-regulated ISGs was also TRAIL, indicating a potential role of the IFN signature in apoptosis. However, a blocking anti-TRAIL Ab did not abrogate apoptosis of CD4(+) T cells in CXCR4-tropic HIV-infected cultures, suggesting the involvement of pathways other than TRAIL mediated. We conclude that acute HIV infection of lymphoid tissue results in up-regulation of ISGs in CD4(+) T cells, which induces an anti-HIV state but not apoptosis.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Simon, Hans-Uwe

ISSN:

0022-1767

ISBN:

17056552

Publisher:

American Association of Immunologists

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:45

Last Modified:

04 May 2014 23:13

PubMed ID:

17056552

Web of Science ID:

000241477400056

URI:

https://boris.unibe.ch/id/eprint/18761 (FactScience: 999)

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