Interferon Induced <i>IFIT</i> Family Genes in Host Antiviral Defense

Zhou, Xiang; Michal, Jennifer J.; Zhang, Lifan; Ding, Bo; Lunney, Joan K.; Liu, Bang; Jiang, Zhihua

doi:10.7150/ijbs.5613

Cited by 204 publications

(199 citation statements)

References 62 publications

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“…However, the exact roles of ISG58 in host defense have yet to be elucidated. From an evolutionary point of view, human ISG58 is different from all the other ISG56 family members: it does not have a mouse homologue, and is the only ISG56 family protein so far identified in birds, marsupials, frogs and fish [5]. ISG58 was found to copurify with a diverse mixture of small RNAs consisting mainly of a subset of tRNAs, and a number of noncoding RNAs [6].…”

Section: Dear Editormentioning

confidence: 99%

Crystal structure and nucleotide selectivity of human IFIT5/ISG58

et al. 2013

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Section: Dear Editormentioning

confidence: 99%

Crystal structure and nucleotide selectivity of human IFIT5/ISG58

et al. 2013

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“…Five proteins in the list of differentially expressed proteins were involved in this defense response. Ifit1, Ifit2, and Ifit3 are members of the family of interferon-induced proteins with tetratricopeptide repeats (IFITs), and Gbp1 and Gbp3 are members of the family of IFN-induced guanylate-binding proteins which are all involved in antiviral responses (23,24). Ifit1 and Ifit3 were differentially expressed in rVV-F-and rVV-G-primed mice, while Ifit2 was found differentially expressed only in rVV-F-primed mice.…”

Section: Resultsmentioning

confidence: 99%

Host Proteome Correlates of Vaccine-Mediated Enhanced Disease in a Mouse Model of Respiratory Syncytial Virus Infection

Diepen

Brand

Waal

et al. 2015

J Virol

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Respiratory syncytial virus (RSV) is Respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract infections in children, being responsible for up to 80% of the cases of acute bronchiolitis and frequent subsequent hospital admission in industrialized countries (1, 2). It has been estimated that RSV causes 33.8 million acute lower respiratory tract infections globally each year, resulting in 66,000 to 199,000 deaths among children under 5 years of age, 99% of which occur in developing countries (3). In addition to young children, immunocompromised individuals and the elderly are at increased risk for severe RSV disease and hospitalization. A licensed RSV vaccine is currently not available, and the development of a vaccine against RSV infection has proven to be very difficult. Formalin-inactivated RSV (FI-RSV) vaccine trials in the 1960s failed to induce protection upon natural RSV infection and even predisposed patients for enhanced disease, resulting in two deaths and hospitalization of 80% of the vaccinated subjects (4-7). Experimental inactivated and subunit vaccines tend to prime for the induction of unbalanced, type 2 T-helper (Th2) host responses that result in enhanced disease accompanied by an influx of inflammatory cells (8). On the other hand, development of live attenuated RSV vaccines that are more likely to induce balanced host responses appears difficult to tune and these live vaccines tend either to be over-or underattenuated (9, 10). Several RSV infection animal models have been developed, and these are exploited for vaccine research and studies on virus-induced (immuno)pathology. Multiple virological and immunological parame-

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“…In addition, orthologs of the IFIT family are evolutionarily conserved from amphibians to mammals. However, the ortholog of human IFIT5 is absent from mouse (6,9). Recent studies indicate that IFIT proteins play an important role in antiviral processes and restrict viral replication through altering protein synthesis, binding to viral RNAs, or interacting with structural or nonstructural viral proteins (8,10,11).…”

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confidence: 99%

“…Humans have a distinct combination of IFIT family genes, including IFIT1 (ISG56), IFIT2 (ISG54), IFIT3 (ISG60), and IFIT5 (ISG58), which are clustered on human chromosome 10 (6). These IFIT proteins are robustly induced by IFNs (mainly IFN-I), viral infection, and lipopolysaccharide and are characterized by the unique helix-turn-helix motifs, called tetratricopeptide repeats, which mediate a variety of protein-protein and protein-RNA interactions (6)(7)(8). In addition, orthologs of the IFIT family are evolutionarily conserved from amphibians to mammals.…”

mentioning

confidence: 99%

“…Recent studies indicate that IFIT proteins play an important role in antiviral processes and restrict viral replication through altering protein synthesis, binding to viral RNAs, or interacting with structural or nonstructural viral proteins (8,10,11). IFIT3 was demonstrated to inhibit the replication of many DNA and RNA viruses, such as hepatitis B virus (HBV), human papillomavirus (HPV), hepatitis C virus (HCV), West Nile virus (WNV), porcine reproductive and respiratory syndrome virus (PRRSV), Dengue virus (DV), vesicular stomatitis virus (VSV), and others (6,(12)(13)(14)(15). For example, in HeLa cells, the replication of VSV, whose genomic and leader RNAs carry 5=-ppp, was inhibited by the ectopic expression of IFIT1, IFIT2, and IFIT3, where they form a complex with each other to efficiently recognize 5=-ppp-RNA (12,16).…”

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confidence: 99%

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Herpes Simplex Virus 1 Tegument Protein UL41 Counteracts IFIT3 Antiviral Innate Immunity

Jiang

Zheng

2016

J Virol

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The interferon-induced protein with tetratricopeptide repeat 3 (IFIT3 or ISG60) is a host-intrinsic antiviral factor that restricts many instances of DNA and RNA virus replication. Herpes simplex virus 1 (HSV-1), a DNA virus bearing a large genome, can encode many viral proteins to counteract the host immune responses. However, whether IFIT3 plays a role upon HSV-1 infection is little known. In this study, we show for the first time that HSV-1 tegument protein UL41, a viral endoribonuclease, plays an important role in inhibiting the antiviral activity of IFIT3. Here, we demonstrated that ectopically expressed IFIT3 could restrict the replication of vesicular stomatitis virus (VSV) but had little effect on the replication of wild-type (WT) HSV-1. Further study showed that WT HSV-1 infection downregulated the expression of IFIT3, and ectopic expression of UL41, but not the immediate-early protein ICP0, notably reduced the expression of IFIT3. The underlying molecular mechanism was that UL41 diminished the accumulation of IFIT3 mRNA to abrogate its antiviral activity. In addition, our results illustrated that ectopic expression of IFIT3 inhibited the replication of UL41-null mutant virus (R2621), and stable knockdown of IFIT3 facilitated its replication. Taking these findings together, HSV-1 was shown for the first time to evade the antiviral function of IFIT3 via UL41. IMPORTANCEThe tegument protein UL41 of HSV-1 is an endoribonuclease with the substrate specificity of RNase A, which plays an important role in viral infection. Upon HSV-1 infection, interferons are critical cytokines that regulate immune responses against viral infection. Host antiviral responses are significantly boosted or crippled in the presence or absence of IFIT3; however, whether IFIT3 plays a role during HSV-1 infection is still unknown. Our data show for the first time that IFIT3 has little effect on HSV-1 replication, as UL41 decreases the accumulation of IFIT3 mRNA and subverts its antiviral activity. This study identifies IFIT3 as a novel target of the tegument protein UL41 and provides new insight into HSV-1-mediated immune evasion.

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Interferon Induced IFIT Family Genes in Host Antiviral Defense

Cited by 204 publications

References 62 publications

Crystal structure and nucleotide selectivity of human IFIT5/ISG58

Crystal structure and nucleotide selectivity of human IFIT5/ISG58

Host Proteome Correlates of Vaccine-Mediated Enhanced Disease in a Mouse Model of Respiratory Syncytial Virus Infection

Herpes Simplex Virus 1 Tegument Protein UL41 Counteracts IFIT3 Antiviral Innate Immunity

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