Systematic identification of type I and type II interferon-induced antiviral factors

Abstract

Type I and type II interferons (IFNs) are cytokines that establish the cellular antiviral state through the induction of IFN-stimulated genes (ISGs). We sought to understand the basis of the antiviral activity induced by type I and II IFNs in relation to the functions of their ISGs. Based on gene expression studies, we systematically identified antiviral ISGs by performing blinded, functional screens on 288 type I and type II ISGs. We assessed and validated the antiviral activity of these ISGs against an RNA virus, vesicular stomatitis virus (VSV), and a DNA virus, murine gammaherpes virus (MHV-68). Overall, we identified 34 ISGs that elicited an antiviral effect on the replication of either one or both viruses. Fourteen ISGs have uncharacterized antiviral functions. We further defined ISGs that affect critical life-cycle processes in expression of VSV protein and MHV-68 immediate-early genes. Two previously undescribed antiviral ISGs, TAP1 and BMP2, were further validated. TAP1-deficient fibroblasts were more susceptible to VSV infection but less so to MHV-68 infection. On the other hand, exogenous BMP2 inhibits MHV-68 lytic growth but did not affect VSV growth. These results delineate common and distinct sets of type I and type II IFN-induced genes as well as identify unique ISGs that have either broad or specific antiviral effects on these viruses.

IFN-Stimulated Gene LY6E in Monocytes Regulates the CD14/TLR4 Pathway but Inadequately Restrains the Hyperactivation of Monocytes during Chronic HIV-1 Infection

“…Reports indicate that LY6E enhances the replication of yellow fever virus in STAT1 2/2 fibroblasts and Huh-7 cells but does not significantly affect replication of West Nile virus (8,36). Besides, LY6E could restrict vesicular stomatitis virus replication (37). In vitro whole-genome analysis identified a susceptibility locus on human HSA8q24 that exerts influence on the cellular susceptibility to HIV-1.…”

PARP12, an Interferon-stimulated Gene Involved in the Control of Protein Translation and Inflammation

“…PARP12 has been recently identified as a putative anti-viral gene, belonging to a large family of interferonstimulated genes (ISGs) whose expression is often induced during viral infections (11,12). More recently, expression of PARP12 was also found elevated in tissues from mice subjected to bacterial superantigen-(SEB) mediated toxic shock (13), suggesting a potential role of this protein during immune activation.…”

ATF3 Is a Key Regulator of Macrophage IFN Responses

“…Type I IFNs signal via the IFN-a/b receptor (IFNAR), which induces the expression of IFN-stimulated genes (ISGs), encoding proteins with diverse antiviral functions (5,6). Genome-wide transcriptional analysis of IFN-treated cells has revealed the existence of hundreds of ISGs, of which only a few have been characterized to date (7)(8)(9)(10). The production of type I IFNs by pattern recognition receptors (PRRs) and the subsequent expression of ISGs are therefore critical for host protection, and, not surprisingly, mice and humans with defects in IFN responses are more susceptible to viral infections (11)(12)(13).…”