IFIT1 Differentially Interferes with Translation and Replication of Alphavirus Genomes and Promotes Induction of Type I Interferon

Reynaud, Joséphine M.; Kim, Dal–Young; Atasheva, Svetlana; Rasalouskaya, Aliaksandra; White, James P.; Diamond, Michael S.; Weaver, Scott C.; Frolova, Elena I.; Frolov, Ilya

doi:10.1371/journal.ppat.1004863

Cited by 95 publications

(108 citation statements)

References 67 publications

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“…Researches has demonstrated that IFIT1 can restrict HCV growth by inhibiting HCV replication, and the expression level of IFIT1 can be potential biomarker of response to IFNα in patients with HCV[29,38]. IFIT1 restricts the translation and replication of many other viruses such as HPV, HIV and alphavirus, and promotes the induction of IFNα to enhance immune response[18,39,40]. All these evidences demonstrate the importance of IFIT1 in immune system and virus inhibition.…”

Section: Discussionmentioning

confidence: 99%

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IFIT1polymorphisms predict interferon-α treatment efficiency for hepatitis B virus infection

Xie¹,

Wang²,

Yang³

et al. 2016

WJG

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AIMTo investigate the association between interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) polymorphisms and interferon-α (IFNα) treatment efficiency among Chinese hepatitis B virus (HBV) infection patients.METHODSTwo hundred and twenty five newly diagnosed chronic hepatitis B (CHB) patients were enrolled in the study. All of these patients received IFNα treatment for a course of 48 wk, and were followed up for 24 wk after the treatment was end. Clinical information about virological response, hepatitis B e antigen (HBeAg) seroconversion rate and combined response at the end of the treatment, as well as the sustained response by the time of following up 24 wk after the treatment, was collected. Four tag-single nucleotide polymorphisms (SNPs) of IFIT1 were selected and assessed for their association with these clinical outcomes.RESULTSAt the end of the treatment, HBeAg seroconversion was observed in 27.1% patients. Thirty-six point nine percent patients achieved virological response, and 15.6% patients exhibited combined response. Sustained response was obtained in 26.2% patients. The main HBV genotype of the study was genotype B. Patients who infected with HBV genotype B or C showed better treatment efficiency, no matter which clinical outcome was considered. Among the four SNPs assessed, rs303218 (A > G) was found to be significantly associated with the end point virological response when assuming additive model [OR = 0.64 (95%CI: 0.42-0.96), P = 0.032]. Patients who carried rs303218 GG genotype had a rather higher rate of achieving virological response (response rate: 52%, OR = 0.40, 95%CI: 0.18-0.91; P = 0.028) when compared to those had AA genotype (response rate: 27%). The most significant interaction was observed in patients who had relative lower baseline aspartate transaminase. No association between SNPs and HBeAg seroconversion, combined response or sustained response was observed.CONCLUSIONIFIT1 involves in the regulation of IFNα treatment for CHB and its polymorphism rs303218 can predict the end point virological response. The finding requires further validation.

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Section: Discussionmentioning

confidence: 99%

“…It is reported that IFIT1 acts as an important innate immune bottleneck which shows positive regulation on downstream genes[17]. High level of type I IFN is observed in IFIT1-expressing cells[18]. Researches have indicated that the antiviral activity of IFIT1 is modulated by 2’-O methylation of viral RNA.…”

Section: Introductionmentioning

confidence: 99%

IFIT1polymorphisms predict interferon-α treatment efficiency for hepatitis B virus infection

Xie¹,

Wang²,

Yang³

et al. 2016

WJG

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“…GFP also was included in the genome of all viruses to allow visualization of virus infection both in vitro and in vivo. Alphaviruses expressing recombinant proteins through a second subgenomic promoter have been well characterized and have been shown to be useful for tracking viral replication and spread (33,(44)(45)(46). RT-PCR and DNA sequencing of RT-PCR products confirmed that rescued viruses maintained their chimeric composition (data not shown).…”

Section: Chikv/sfv But Not Chikv/veev E2 Chimeras Can Be Rescued Andmentioning

confidence: 95%

Dissecting the Role of E2 Protein Domains in Alphavirus Pathogenicity

Weger-Lucarelli

Aliota

Wlodarchak

et al. 2016

J Virol

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Alphaviruses represent a diverse set of arboviruses, many of which are important pathogens. Chikungunya virus (CHIKV), an arthritis-inducing alphavirus, is the cause of a massive ongoing outbreak in the Caribbean and South America. In contrast to CHIKV, other related alphaviruses, such as Venezuelan equine encephalitis virus (VEEV) and Semliki Forest virus (SFV), can cause encephalitic disease. E2, the receptor binding protein, has been implicated as a determinant in cell tropism, host range, pathogenicity, and immunogenicity. Previous reports also have demonstrated that E2 contains residues important for host range expansions and monoclonal antibody binding; however, little is known about what role each protein domain (e.g., A, B, and C) of E2 plays on these factors. Therefore, we constructed chimeric cDNA clones between CHIKV and VEEV or SFV to probe the effect of each domain on pathogenicity in vitro and in vivo. CHIKV chimeras containing each of the domains of the E2 (⌬DomA, ⌬DomB, and ⌬DomC) from SFV, but not VEEV, were successfully rescued. Interestingly, while all chimeric viruses were attenuated compared to CHIKV in mice, ⌬DomB virus showed similar rates of infection and dissemination in Aedes aegypti mosquitoes, suggesting differing roles for the E2 protein in different hosts. In contrast to CHIKV; ⌬DomB, and to a lesser extent ⌬DomA, caused neuron degeneration and demyelination in mice infected intracranially, suggesting a shift toward a phenotype similar to SFV. Thus, chimeric CHIKV/SFV provide insights on the role the alphavirus E2 protein plays on pathogenesis. T he alphaviruses represent a diverse family of arthropod-borne viruses (arboviruses), many of which are important veterinary or human pathogens. Their transmission cycles involve both an arthropod vector and vertebrate host, resulting in unique evolutionary restrictions. The genus Alphavirus (family Togaviridae) currently includes 29 species that are grouped into 10 complexes based on antigenic, genetic, and/or geographic similarities (1). The aquatic alphaviruses infect marine mammals and have been isolated in lice, although their role as a vector remains unknown (2). The New World alphaviruses include important veterinary and human pathogens, such as the equine encephalitis viruses, Venezuelan (VEEV), eastern (EEEV), and western (WEEV), all of which cause fatal encephalitic disease in both humans and animals such as horses and birds (3). The Old World alphaviruses, present mostly in Africa and Southeast Asia, are commonly associated with arthritic disease, fever, and rash. IMPORTANCE Chikungunya virus (CHIKV) has caused large outbreaks of acute and chronic arthritis throughout Africa and SoutheastChikungunya virus (CHIKV) is the most medically relevant Old World alphavirus and is the current cause of an outbreak of arthritic disease in the Americas, with more than 1 million cases in at least 44 countries, including the United States (4). CHIKV, which reemerged in 2004, has previously caused explosive epidemics of acute and chronic ...

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“…During the host response to infection, secretion of IFN-β or IFN-α engages the type I IFN receptor complex activating the JAK/STAT signaling cascade leading to upregulation of antiviral interferon stimulation genes (ISGs) that inhibit alphavirus replication [29–33]. Alphaviruses are known to suppress the induction of the innate immune response during infection through different mechanisms.…”

Section: Viral Antagonism Of the Innate Immune Responsementioning

confidence: 99%

“…The activity of the translation-inhibiting ISG, IFIT-1, is limited by the lack of free nucleotides in the 5’ NTR of VEEV and the presence of a rigid stem-loop structure. This prevents the recognition of the virus type 0 cap structure by IFIT-1 and inhibition of virus translation [31,33]. Mutations in the 5’ NTR secondary structure present in the attenuated TC-83 vaccine strain lead to IFIT-1 recognition of VEEV RNA and in vivo attenuation [31].…”

Section: Viral Antagonism Of the Innate Immune Responsementioning

confidence: 99%

Alphaviruses suppress host immunity by preventing myeloid cell replication and antagonizing innate immune responses

Trobaugh

Klimstra

2017

Current Opinion in Virology

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Alphaviruses are medically important mosquito-borne viruses that cause a range of diseases in humans from febrile illness to arthritis or encephalitis. The innate immune response functions to suppress virus replication through upregulation of antiviral molecules and contributes to development of the adaptive immune response. Myeloid cells act as master regulators of virus infection by initiating both the innate and adaptive immune responses. Alphaviruses are capable of antagonizing individual components of these responses to increase replicative fitness in vivo. However, recently, studies have demonstrated that some alphaviruses avoid myeloid cell replication altogether to achieve a similar effect. In this review, we summarize how alphaviruses evade myeloid cell infection and individual inductive mechanisms, thereby limiting the activation of the innate immune response.

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IFIT1 Differentially Interferes with Translation and Replication of Alphavirus Genomes and Promotes Induction of Type I Interferon

Cited by 95 publications

References 67 publications

IFIT1polymorphisms predict interferon-α treatment efficiency for hepatitis B virus infection

IFIT1polymorphisms predict interferon-α treatment efficiency for hepatitis B virus infection

Dissecting the Role of E2 Protein Domains in Alphavirus Pathogenicity

Alphaviruses suppress host immunity by preventing myeloid cell replication and antagonizing innate immune responses

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