Enteroviruses have been suggested as triggers of type 1 diabetes (T1D). We aimed to assess whether established T1D susceptibility single nucleotide polymorphisms (SNPs) and candidate SNPs in innate immune genes were associated with the frequency of enterovirus infection in otherwise healthy children. Fifty-six established T1D SNPs and 97 other candidate immunity SNPs were typed in 419 children carrying the T1D high-risk genotype, HLA-DR4-DQ8/DR3-DQ2 genotype, and 373 children without this genotype. Enteroviral RNA was detected using real-time polymerase chain reaction, with primers detecting essentially all enterovirus serotypes, in 7,393 longitudinal stool samples collected monthly (age range 3-36 months). The most significant association was with two T1D SNPs, rs12150079 (ZPBP2/ORMDL3/GSDMB region) (enterovirus frequency: AA 7.3%, AG 8.7%, GG 9.7%, RR = 0.86, overall p = 1.87E-02) and rs229541 (C1QTNF6/SSTR3/RAC2) (enterovirus frequency: CC 7.8%, CT 9.7%, TT 9.4%, RR = 1.13, overall p = 3.6E-02), followed by TLR8 (rs2407992) (p = 3.8E-02), TLR3 (1914926) (p = 4.9E-02), and two other T1D SNPs (IFIH1 rs3747517, p = 4.9E-02 and PTPN22, rs2476601, p = 5.3E-02). However, the quantile-quantile plot of p-values with confidence intervals for all 153 SNPs did not reveal clear evidence for rejection of the complete null hypothesis. Among a number of SNPs in candidate genes, we found no evidence for strong associations with enterovirus presence in stool samples from Norwegian children.
- MeSH
- enterovirové infekce epidemiologie genetika MeSH
- Enterovirus izolace a purifikace MeSH
- feces virologie MeSH
- genetická predispozice k nemoci * MeSH
- genetické asociační studie MeSH
- jednonukleotidový polymorfismus MeSH
- kojenec MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé MeSH
- longitudinální studie MeSH
- předškolní dítě MeSH
- RNA virová analýza genetika MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Norsko MeSH
Viral CC chemokine inhibitor (vCCI) of the clone P13 vaccinia virus (VACV) strain PRAHA lacks eight amino acids in the signal peptide sequence. To study the influence of vCCI on virus biology, a virus with the vCCI gene coding for a prolonged signal sequence was prepared. We found that secreted vCCI attenuated the virus in vivo, and that it correlated with decreased levels of RANTES, eotaxin, TARC, and MDC in the blood in comparison with the parental virus. We determined the influence of vCCI on the CTL response against VACV E3((140-148)) (VGPSNSPTF) and HPV16 E7((49-57)) (RAHYNIVTF) H-2D(b)-restricted epitopes. The examination of the specific CTL response elicited by immunization with the recombinant VACV-expressing tumor-associated HPV16 E7 antigen by IFN-γ ELISPOT showed that the immunogenicity of the recombinant VACV-producing secretory vCCI was similar to that of the parent virus or deletion mutant in the C23L/B29R locus. Immunization with the secretory vCCI-producing recombinant virus has a lower therapeutic anti-tumor effect against TC-1 tumors. Viral CCI downregulated the E7-specific response induced by gene gun immunization with the DNA vaccines pBSC-SigE7 LAMP and pBSC-vCCI. We also observed that the immune response against vCCI elicited by the DNA vaccine did not affect the multiplication of VACV in vivo.
- MeSH
- buněčné linie MeSH
- chemokin CCL17 krev MeSH
- chemokin CCL5 krev MeSH
- chemokiny CC antagonisté a inhibitory krev MeSH
- cytotoxické T-lymfocyty imunologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové supresorové proteiny krev MeSH
- Papillomavirus E7 - proteiny genetika imunologie MeSH
- proteiny ADAM krev MeSH
- protinádorové vakcíny genetika imunologie MeSH
- sekvenční delece MeSH
- syntetické vakcíny genetika imunologie MeSH
- vakcinace MeSH
- virové proteiny genetika metabolismus MeSH
- virové vakcíny imunologie MeSH
- virus vakcinie genetika imunologie patogenita MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Enterovirus infections may be involved in the etiology of type 1 diabetes (T1D), which is strongly associated with certain human leukocyte antigen (HLA) class II haplotypes. Our aim was to assess whether HLA genotypes conferring varying degrees of risk for T1D were associated with enterovirus gut infections. From the general Norwegian population, 190 healthy infants at high-risk for T1D (DR4-DQ8/DR3-DQ2), and 383 infants without this genotype were identified. Non-DR4-DQ8/DR3-DQ2 genotypes were further categorized as conferring either an increased-to-moderate risk (DR4-DQ8 or DR3-DQ2), were protective (DQB1*06:02), or were neutral (all other genotypes). A total of 4626 monthly fecal samples taken between age 3 and 12mo were tested for enterovirus RNA using real-time PCR. Enterovirus prevalence was 11.5% among high-risk children, and 12.2% in other children (adjusted odds ratio: 1.23, p=0.12). The prevalence was 11.3% in those with increased-to-moderate risk, 13.0% in the protective group, and 12.6% in the neutral group (likelihood ratio test, 3 d.f.: p=0.37). In conclusion, there was no statistically significant association between HLA genotype and the occurrence of human enterovirus gut infections.
- MeSH
- diabetes mellitus 1. typu genetika virologie MeSH
- enterovirové infekce * MeSH
- Enterovirus genetika izolace a purifikace MeSH
- feces * virologie MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- HLA-DQ alfa řetězec * genetika MeSH
- HLA-DQ beta řetězec * genetika MeSH
- HLA-DRB1 řetězec * genetika MeSH
- kojenec MeSH
- lidé MeSH
- testování histokompatibility MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- MeSH
- ekosystém MeSH
- hmyz - vektory virologie MeSH
- lidé MeSH
- nemoci ptáků epidemiologie virologie MeSH
- virus západního Nilu izolace a purifikace MeSH
- západonilská horečka epidemiologie přenos veterinární MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
- Geografické názvy
- Evropa MeSH
- Severní Amerika MeSH
- MeSH
- B-lymfocyty imunologie klasifikace MeSH
- buněčné linie MeSH
- DNA virů biosyntéza krev MeSH
- Gammaherpesvirinae genetika imunologie izolace a purifikace MeSH
- Herpesviridae imunologie MeSH
- imunofenotypizace MeSH
- myši MeSH
- slezina cytologie imunologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
