LAUSR

It is well known that the release of type-I interferons, IFNa and IFNb in response to infection is a “tightrope walk” since they may act as either friend or foe. On one hand, type-I IFNs induce an antiviral state in host cells during early infection, preventing viral spread. On the other hand, their pro-inflammatory activity can have detrimental effects, particularly during chronic infections [1-3]. Owing to their antiviral and immune-modulatory properties, type-I IFNs may hold therapeutic potential for viral infections, such as human immunodeficiency virus (HIV). Clinical studies in which antiretroviral therapy (ART) was combined with an application of pegylated (Peg)-IFNa2a produced promising results, evidenced by suppressed HIV viremia and reduction in levels of genome-integrated HIV DNA [4]. However, to effectively exploit this antiviral potential of type-I IFNs, while avoiding undesirable side effects including immune pathology, it is essential to understand the timing and conditions that mediate these opposing effects of type-I IFNs from beneficial to damaging during the course of viral infections [5]. Besides, there is a gap in our knowledge of how type-I IFNs act on the host glycosylation machinery to induce inflammatory processes. In an article in EBioMedicine, Giron and colleagues address the dual role of type-I IFNs by investigating the impact of Peg-IFNa2a treatment on host glycosylation during ART-suppressed chronic HIV infection [6]. To this end, the authors profiled IgG glycome as well as cell surface glycomic signatures of CD8 T cells and NK cells in peripheral blood mononuclear cells (PBMCs) from 18 HIV-infected individuals treated with a combination of ART and Peg-IFNa2a. To correlate IFNa-mediated changes in the glycomic signatures with inflammatory response, the authors measured proand anti-inflammatory cytokines and soluble markers in plasma as well as activation markers expressed by CD8 T cells and NK cells. Interestingly, significant changes occurred in the glycan traits after five weeks of starting