Correlation of OAS1 Gene Polymorphism at Exon 7 Splice Accepter Site with Interferon-Based Therapy of HCV Infection in Pakistan

ImranMuhammad,; ManzoorSobia,; Mahmood, KhattakNasir; TariqMuqddas,; Khalid, Madiha; JavedFarakh,; BhattiShameem,

doi:10.1089/vim.2013.0107

Cited by 17 publications

(6 citation statements)

References 49 publications

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“…In contrast, those CC-RIX mice homozygous for a wild-type-derived allele showed asymptomatic disease outcomes. These observations serve to validate the important previous studies that first defined the genetic relationship of Oas1b with enhanced susceptibility to WNV ( 5 , 35 , 39 ), and thus underscore the promising application of the CC mouse model for future genetic studies to identify host genes of WNV susceptibility and resistance.…”

Section: Resultssupporting

confidence: 73%

“…As mentioned above, polymorphisms at Oas1b have been shown to drive resistance to flaviviral infections in mice ( 37 , 40 ). Furthermore, genetic variation in OAS family members, such as Oas1 , the putative human homologue to Oas1b , have been shown to influence WNV disease ( 41 ), as well as dengue ( 42 ) and hepatitis C virus ( 39 ) in humans. However, despite the dominant role of Oas1/Oas1b in these populations in driving overall symptoms/susceptibility to WNV, there remains a range of pathogenic differences in both the human population as well as in our CC RIX lines, even among CC RIX group with identical Oas1b allele classifications.…”

Section: Discussionmentioning

confidence: 99%

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Genetic Diversity in the Collaborative Cross Model Recapitulates Human West Nile Virus Disease Outcomes

Graham

Thomas

Swarts

et al. 2015

mBio

112

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West Nile virus (WNV) is an emerging neuroinvasive flavivirus that now causes significant morbidity and mortality worldwide. The innate and adaptive immune responses to WNV infection have been well studied in C57BL/6J inbred mice, but this model lacks the variations in susceptibility, immunity, and outcome to WNV infection that are observed in humans, thus limiting its usefulness to understand the mechanisms of WNV infection and immunity dynamics. To build a model of WNV infection that captures human infection outcomes, we have used the Collaborative Cross (CC) mouse model. We show that this model, which recapitulates the genetic diversity of the human population, demonstrates diversity in susceptibility and outcomes of WNV infection observed in humans. Using multiple F1 crosses of CC mice, we identified a wide range of susceptibilities to infection, as demonstrated through differences in survival, clinical disease score, viral titer, and innate and adaptive immune responses in both peripheral tissues and the central nervous system. Additionally, we examined the Oas1b alleles in the CC mice and confirmed the previous finding that Oas1b plays a role in susceptibility to WNV; however, even within a given Oas1b allele status, we identified a wide range of strain-specific WNV-associated phenotypes. These results confirmed that the CC model is effective for identifying a repertoire of host genes involved in WNV resistance and susceptibility. The CC effectively models a wide range of WNV clinical, virologic, and immune phenotypes, thus overcoming the limitations of the traditional C57BL/6J model, allowing genetic and mechanistic studies of WNV infection and immunity in differently susceptible populations.

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Section: Resultssupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Genetic Diversity in the Collaborative Cross Model Recapitulates Human West Nile Virus Disease Outcomes

Graham

Thomas

Swarts

et al. 2015

mBio

112

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“…An abundance of studies have demonstrated that OAS1 and OASL exhibit antiviral effects against various viruses through different pathways and mechanisms [Kwon et al, 2013;Lee et al, 2013a,b;Deo et al, 2014;Imran et al, 2014;Zhu et al, 2014]. Based on the results of the co-silencing of the OAS and RNase L genes, it was confirmed that porcine OAS1 and OAS2 function through the IFN-a/OAS antiviral pathway, and that OASL functions through some other antiviral pathway.…”

Section: Discussionmentioning

confidence: 98%

Porcine 2′, 5′‐oligoadenylate synthetases inhibit Japanese encephalitis virus replication in vitro

Sheng

Zhu

Xue

et al. 2015

Journal of Medical Virology

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The 2', 5'-oligoadenylate synthetases (OAS) are antiviral proteins and several isoforms have been identified as flavivirus-resistance biomarkers in human and mouse. The expression kinetics and antiviral functions of porcine OAS family (OAS1, OAS2, and OASL) in PK-15 cells following infection by Japanese encephalitis virus (JEV) were evaluated in the present study. The endogenous expression of the three OAS genes was efficiently induced by IFN-α treatment in PK-15 cells. However, expression of pOAS1 and pOAS2 responded more quickly than pOASL. Infection by JEV also induced the expression of the pOAS isoforms, but at a significantly lower level than that observed following IFN-α stimulation. Transient overexpression of pOASL and pOAS1 inhibited JEV replication more efficiently than OAS2 overexpression. Interestingly, knockdown of pOAS2 expression by siRNA treatment led to the highest increase in JEV multiplication. Co-silencing of RNase L and each pOAS revealed that the anti-JEV function of pOAS1 and pOAS2 were RNase L dependent, while the antiviral activity of pOASL was not. In conclusion, all pOAS isoforms play a significant role in the response to JEV infection, and are differentially induced by different stimuli. The alternative pathways of antiviral activity stimulated by OASL require further study.

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“…Consistent with the important role of OAS proteins in viral infection, it was shown that polymorphisms in the OAS genes are associated with increased susceptibility to HCV infection[18] and IFN treatment outcomes[17,19,20]. However, the molecular basis for this association is not well understood.…”

Section: Discussionmentioning

confidence: 99%

“…The human OAS family contains the OAS1, OAS2, OAS3, and OASL genes, which are located on chromosome 12 (in the 12q24.1 region)[15,16]. Single-nucleotide polymorphisms (SNPs) in the OAS family genes have been identified as a factor associated with susceptibility to viral infection and antiviral effects during IFN-based therapy in patients infected with HCV[17-20]. …”

Section: Introductionmentioning

confidence: 99%

Impact of IL28B and OAS gene family polymorphisms on interferon treatment response in Caucasian children chronically infected with hepatitis B virus

Domagalski¹,

Pawłowska²,

Zaleśna³

et al. 2016

WJG

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AIMTo investigate the impact of IL28B and OAS gene polymorphisms on interferon treatment responses in children with chronic hepatitis B.METHODSWe enrolled 52 children (between the ages of 4 and 18) with hepatitis B e antigen-negative chronic hepatitis B (CHB), who were treated with pegylated interferon alfa for 48 wk. Single nucleotide polymorphisms in the OAS1 (rs1131476), OAS2 (rs1293747), OAS3 (rs2072136), OASL (rs10849829) and IL28B (rs12979860, rs12980275 and rs8099917) genes were studied to examine their associations with responses to IFN treatment in paediatric patients. We adopted two criteria for the therapeutic response, achieving an hepatitis B virus (HBV) DNA level < 2000 IU/mL and normalization of ALT activity (< 40 IU/L). To perform the analyses, we compared the patients in terms of achieving a partial response (PR) and a complete response (CR) upon measurement at the 24-wk post-treatment follow-up.RESULTSThe PR and CR rates were 80.8% and 42.3%, respectively. Factors such as age, gender and liver histology had no impact on the type of response (partial or complete). A statistically significant relationship between higher baseline HBV DNA and ALT activity levels and lower rates of PR and CR was shown (P < 0.05). The allele association analysis revealed that only the IL-28B rs12979860 (C vs T) and IL28B rs12980275 (A vs G) markers significantly affected the achievement of PR (P = 0.021, OR = 3.3, 95%CI: 1.2-9.2 and P = 0.014, OR = 3.7, 95%CI: 1.3-10.1, respectively). However, in the genotype analysis, only IL-28B rs12980275 was significantly associated with PR (AA vs AG-GG, P = 0.014, OR = 10.9, 95%CI: 1.3-93.9). The association analysis for CR showed that the TT genotype of IL28B rs12979860 was present only in the no-CR group (P = 0.033) and the AA genotype of OASL rs10849829 was significantly more frequent in the no-CR group (P = 0.044, OR = 0.26, 95%CI: 0.07-0.88). The haplotype analysis revealed significant associations between PR and CR and OAS haplotype (P = 0.0002 and P = 0.001, respectively), but no association with IL28B haplotype was observed.CONCLUSIONIL28B and OAS polymorphisms are associated with different clinical outcomes in CHB children treated with interferon.

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Correlation of OAS1 Gene Polymorphism at Exon 7 Splice Accepter Site with Interferon-Based Therapy of HCV Infection in Pakistan

Cited by 17 publications

References 49 publications

Genetic Diversity in the Collaborative Cross Model Recapitulates Human West Nile Virus Disease Outcomes

Genetic Diversity in the Collaborative Cross Model Recapitulates Human West Nile Virus Disease Outcomes

Porcine 2′, 5′‐oligoadenylate synthetases inhibit Japanese encephalitis virus replication in vitro

Impact of IL28B and OAS gene family polymorphisms on interferon treatment response in Caucasian children chronically infected with hepatitis B virus

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