Purpose of review To explore new data from recent studies addressing the role of co-infections in immune activation in HIV-1 infected patients, with a focus on Immune Reconstitution Inflammatory Syndrome (IRIS), an aberrant inflammatory response occurring shortly after antiretroviral therapy (ART) initiation. Recent findings Chronic HIV infection is associated with a number of co-infections that contribute to immune activation in various settings including early after ART initiation in the most noticeable form of IRIS and also in chronic treated infection, with chronic viral infections like CMV and HCV or HBV contributing to immune activation and also morbidity and mortality. Expanding on older studies, the role of T cells in IRIS has been further elucidated with evidence of more pronounced effector activity in IRIS patients that may be leading to excessive tissue pathology. Newer studies are also continuing to shed light on the role of myeloid cells in IRIS as well as the contribution of antigen load in the syndrome. In addition, preliminary data are beginning to suggest a possible role of inflammasome formation in IRIS. In cryptococcal IRIS, the role of activated immune cells (T cell and myeloid) and biomarkers were evaluated in more detail at the site of infection (CSF). Finally, important differences of patients developing IRIS versus those who die from TB despite ART initiation were reported, a distinction that may have important implications for participant selection in studies aiming to prevent IRIS with immunosuppressive agents. Summary Better understanding of the role of opportunistic infections at ART initiation and IRIS pathogenesis will assist in improved strategies for prevention and treatment. The long-term consequences of IRIS remain unclear. Chronic viral coinfections with herpesviruses and HCV are important factors in persistent immune activation in chronic treated HIV.

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Islet antigen (IA)-2, IA-2b, and glutamate decarboxylase (GAD65) are major autoantigens in type 1 diabetes (T1D). Autoantibodies to these autoantigens appear years before disease onset and are widely used as predictive markers. Little is known, however, about what regulates the expression of these autoantigens. The present experiments were initiated to test the hypothesis that microRNAs (miRNAs) can target and affect the levels of these autoantigens. Bioinformatics was used to identify miRNAs predicted to target the mRNAs coding IA-2, IA2b, and GAD65. RNA interference for the miRNA processing enzyme Dicer1 and individual miRNA mimics and inhibitors were used to confirm the effect in mouse islets and MIN6 cells. We show that the imprinted 14q32 miRNA cluster contains 56 miRNAs, 32 of which are predicted to target the mRNAs of T1D autoantigens and 12 of which are glucose-sensitive. Using miRNA mimics and inhibitors, we confirmed that at least 7 of these miRNAs modulate the mRNA levels of the T1D autoantigens. Dicer1 knockdown significantly reduced the mRNA levels of all 3 autoantigens, further confirming the importance of miRNAs in this regulation. We conclude that miRNAs are involved in regulating the expression of the major T1D autoantigens.-Abuhatzira, L., Xu, H., Tahhan, G., Boulougoura, A., Schäffer, A. A., Notkins, A. L. Multiple microRNAs within the 14q32 cluster target the mRNAs of major type 1 diabetes autoantigens IA-2, IA-2b, and GAD65. FASEB J. 29, 4374-4383 (2015). www.fasebj.org