Inter and intra-host diversity of RSV in hematopoietic stem cell transplant adults with normal and delayed viral clearance.

Respiratory syncytial virus (RSV) infection in immunocompromised individuals often leads to prolonged illness, progression to severe lower respiratory tract infection, and even death. How the host immune environment of the hematopoietic stem cell transplant (HCT) adults can affect viral genetic variation during an acute infection is not understood well. In the present study, we performed whole genome sequencing of RSV/A or RSV/B from samples collected longitudinally from HCT adults with normal (<14 days) and delayed (≥14 days) RSV clearance who were enrolled in a ribavirin trial. We determined the inter-host and intra-host genetic variation of RSV and the effect of mutations on putative glycosylation sites. The inter-host variation of RSV is centered in the attachment (G) and fusion (F) glycoprotein genes followed by polymerase (L) and matrix (M) genes. Interestingly, the overall genetic variation was constant between normal and delayed clearance groups for both RSV/A and RSV/B. Intra-host variation primarily occurred in the G gene followed by non-structural protein (NS1) and L genes; however, gain or loss of stop codons and frameshift mutations appeared only in the G gene and only in the delayed viral clearance group. Potential gain or loss of O-linked glycosylation sites in the G gene occurred both in RSV/A and RSV/B isolates. For RSV F gene, loss of N-linked glycosylation site occurred in three RSV/B isolates within an antigenic epitope. Both oral and aerosolized ribavirin did not cause any mutations in the L gene. In summary, prolonged viral shedding and immune deficiency resulted in RSV variation, especially in structural mutations in the G gene, possibly associated with immune evasion. Therefore, sequencing and monitoring of RSV isolates from immunocompromised patients are crucial as they can create escape mutants that can impact the effectiveness of upcoming vaccines and treatments.

The third international hackathon for applying insights into large-scale genomic composition to use cases in a wide range of organisms.

In October 2021, 59 scientists from 14 countries and 13 U.S. states collaborated virtually in the Third Annual Baylor College of Medicine & DNANexus Structural Variation hackathon. The goal of the hackathon was to advance research on structural variants (SVs) by prototyping and iterating on open-source software. This led to nine hackathon projects focused on diverse genomics research interests, including various SV discovery and genotyping methods, SV sequence reconstruction, and clinically relevant structural variation, including SARS-CoV-2 variants. Repositories for the projects that participated in the hackathon are available at https://github.com/collaborativebioinformatics.

Dectin-1 is required for miR155 upregulation in murine macrophages in response to Candida albicans.

The commensal fungal pathogen Candida albicans is a leading cause of lethal systemic infections in immunocompromised patients. One of the main mechanisms of host immune evasion and virulence by this pathogen is the switch from yeast form to hyphal growth morphologies. Micro RNAs (miRNAs), a small regulatory non-coding RNA, has been identified as an important part of the immune response to a wide variety of pathogens. In general, miRNAs act by modulating the intensity of inflammatory responses. miRNAs act by base-paring binding to specific sequences of target mRNAs, generally causing their silencing through mRNA degradation or translational repression. To study the impact of C. albicans cell morphology upon host miRNA expression, we investigated the differential modulation of 9 different immune response-related miRNAs in primary murine bone marrow-derived macrophages (BMDMs) exposed to either yeasts or hyphal forms of Candida albicans. Here, we show that the different growth morphologies induce distinct miRNA expression patterns in BMDMs. Interestingly, our data suggest that the C-Type lectin receptor Dectin-1 is a major PRR that orchestrates miR155 upregulation in a Syk-dependent manner. Our results suggest that PRR-mediating signaling events are key drivers of miRNA-mediated gene regulation during fungal pathogenesis.