Type 1 diabetes (T1D) results from interplay between genetic predisposition, immune system, and environmental factors. Epidemiological and experimental data strongly suggest a role for enteroviruses in the development of T1D, but a lot of controversies and unanswered questions remained. This review focuses on issues that are fueling debate. Beyond HLA genes, which provide genetic susceptibility for T1D, other loci have been identified to be associated with the disease. There is a link between T1D and single-nucleotide polymorphisms (SNPs) in the interferon-induced helicase 1 (IFIH1) gene that encodes melanoma differentiation-associated protein 5 (MDA5). This protein is a cytoplasmic sensor for viruses especially coxsackieviruses B, the most incriminated enteroviruses in T1D pathogenesis. Upon viral infection, MDA5 stimulates the production of mediators of the innate antiviral immune response, which is believed to play a role in a 'bystander activation' scenario. Rare variants of IFIH1 through a lost or reduced expression of the protein are protective against T1D, whereas common IFIH1 SNPs are associated with the disease. However, a clear association has not been yet established between T1D-associated IFIH1 polymorphisms and enterovirus detection. Literature have accumulated a lot of evidence supporting that enteroviruses can contribute, at least in some patients, to the pathogenesis of T1D through various mechanisms. But it is still a challenge to date to prove a causal relationship between enteroviruses and T1D. Future studies may lead to a better understanding of this relationship and ultimately can help toward disease prevention.

Sanger sequencing of plasma RNA is the standard method for HIV-1 drug resistance testing in treatment-naive patients, but is limited by the non-detection of resistance-associated mutations (RAMs) with prevalence below approximately 20%. We compared RNA and DNA Sanger sequencing (RSS and DSS) with RNA next-generation sequencing (NGS) for RAM detection in HIV-1 reverse transcriptase (RT), protease (PR) and integrase (IN) genes. Sanger sequencing was performed on RNA and DNA, following the recommendations of the French Agency for AIDS Research (ANRS). NGS was performed on RNA using the HIV-1 Drug Resistance Assay, v. 3.0 (Roche) on the 454 GS Junior sequencer. The IAS-USA list was used to identify RAMs. ANRS, Rega and Stanford algorithms were used for drug resistance interpretation. The study included 48 ART-naive patients. The number of patients with at least one major RAM was 3, 3, 4 and 8 when using RSS, DSS, NGS 20% and NGS 5%, respectively. Numerous minor mutations were detected in patients, especially in the protease gene. None of the methods detected any major mutation in the integrase gene. Overall, the mutation detection rate was similar between RSS and DSS, and higher with NGS 20%. Differences in drug resistance interpretation were found between algorithms. No impact of the minority RAMs detected by NGS was found on the short-term treatment outcome. DSS does not clearly improve the detection of RAMs in ART-naive patients, as compared with RSS. NGS allows detection of additional minority RAMs; however, their clinical relevance requires further investigation.

An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in the coronavirus disease pandemic, drastically affecting global health and economy. Though the understanding of the disease has improved, fighting the virus remains challenging. One of the strategies is repurposing existing drugs as inhibitors of SARS-CoV-2. Fluoxetine (FLX), a selective serotonin reuptake inhibitor, reportedly inhibits the replication of RNA viruses, especially Coxsackieviruses B (CVB), such as CV-B4 in vitro and in vivo. Therefore, in this study, we investigated the in vitro antiviral activity of FLX against SARS-CoV-2 in a model of acute infection. When 10 μM of FLX was added to SARS-CoV-2-infected Vero E6 cells, the virus-induced cytopathic effect was not observed. In this model, the level of infectious particles in the supernatant was lower than that in controls. The level was below the limit of detection of the assay up to day 3 post-infection when FLX was administered before viral inoculation or simultaneously followed by daily inoculation. In conclusion, FLX can inhibit SARS-CoV-2 in vitro. Further studies are needed to investigate the potential value of FLX to combat SARS-CoV-2 infections, treat SARS-CoV-2-induced diseases, and explain the antiviral mechanism of this molecule to pave way for novel treatment strategies.