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. 2009 Dec;1(3):545-73.
doi: 10.3390/v1030545. Epub 2009 Oct 27.

Effect of type-I interferon on retroviruses

Esperanza Gómez-Lucía  1 , Victorio M Collado, Guadalupe Miró, Ana Doménech
Affiliations

Effect of type-I interferon on retroviruses

Esperanza Gómez-Lucía et al. Viruses. 2009 Dec.

Abstract

Type-I interferons (IFN-I) play an important role in the innate immune response to several retroviruses. They seem to be effective in controlling the in vivo infection, though many of the clinical signs of retroviral infection may be due to their continual presence which over-stimulates the immune system and activates apoptosis. IFN-I not only affect the immune system, but also operate directly on virus replication. Most data suggest that the in vitro treatment with IFN-I of retrovirus infected cells inhibits the final stages of virogenesis, avoiding the correct assembly of viral particles and their budding, even though the mechanism is not well understood. However, in some retroviruses IFN-I may also act at a previous stage as some retroviral LTRs posses sequences homologous to the IFN-stimulated response element (ISRE). When stimulated, ISREs control viral transcription. HIV-1 displays several mechanisms for evading IFN-I, such as through Tat and Nef. Besides IFN-α and IFN-β, some other type I IFN, such as IFN-τ and IFN-ω, have potent antiviral activity and are promising treatment drugs.

Keywords: FeLV; HIV-1; HTLV-I; ISRE; MuLV; Type-I interferons; retrovirus.

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Figures

Figure 1.
Figure 1.
A) Schematic representation of the genomic structure of HIV-1, B) Blow-up of the two Long Terminal Repeats (LTR) which flank the proviral sequence, C) Some of the regulatory elements in the 5′ LTR, showing the sequence of the Interferon-Stimulated Response Elements (ISRE).
Figure 2.
Figure 2.
Simplified mechanism of regulation of the induction of the interferon genes in most cells. PKR, RNA dependent protein kinase; IRF, interferon regulatory factor; ISGF, IFN-stimulated gene factor; IFNAR, interferon alpha receptor; ISRE, interferon stimulated response elements. Ovals represent proteins, squares represent genes.
Figure 3.
Figure 3.
Simplified mechanism of regulation of the induction of the interferon genes in dendritic cells. IRF, interferon regulatory factor. Ovals represent proteins, squares represent genes.
Figure 4.
Figure 4.
Induction mechanism of genes by type I interferons. IFNAR, IFN-α receptor; IRF, interferon regulatory factor; ISGF, IFN-stimulated gene factor; ISRE, interferon-stimulated response element; TYK, tyrosine kinase; JAK, Janus kinase; STAT, Signal Transduction and Activator of Transcription.
Figure 5.
Figure 5.
Mechanisms by which viruses circumvent the effect of IFN. 1. Competition with IFN for receptors (IFNAR); 2. Inhibition of IFN synthesis and secretion; 3. Inhibition of the IFN signaling, which may happen at different levels; 4. Inhibition of the proteins stimulated by IFN, mostly of the PKR system.
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