Immunology

Biography

Biography: Ammira S Al-Shabeeb AKIL

Abstract

There is no longer a question as to whether viruses contribute to the pathogenesis of type 1diabetes (T1D). We now have evidence using next generation sequencing (NGS) of enteroviruses EVs isolated from children with islet autoimmunity (IA) demonstrating up to 10% change in the viral genome at the nucleotide level 10 days after inoculation into human islets. NGS:Full-length EV genomes were amplified as a single 7.4 kb fragment by RT-PCR, and NGS performed using the Illumina MiSeq sequencer. Phylogenetic analysis of the full-length viral consensus sequences performed using the neighbour joining and maximum likelihood method. Trees were constructed from alignment of complete genome sequences by using best-fit models and visualised using FigTree. Comparisons were performed with Viral Epidemiology Signature Pattern Analysis (VESPA). Two of the EVs from IA+ cases had an N to S amino acid (AA) substitution within the 2C protein, which became dominant after 10 days passage in the islets. EV isolate from another IA+ case has 5 AA differences within the capsid protein VP4 at residues 3, 16, 18, 50 and 61. VP4 has been shown in vitro to be a target of human antibodies that enhance CVB induced synthesis of interferon α (IFN-α). Antibodies directed towards the region 11-30 of the VP4 capsid enhance infection of peripheral blood cells with CVB4 in vitro. Therefore, our preliminary data suggest VP4 may be a determinant of ‘diabetogenicity’. Our novel NGS data will contribute to vaccine development from a global perspective and then reduce the future burden of T1D.