Sullender, M. | bioRxiv Science

bioRxiv2025

Trim47 inhibits murine norovirus replication in a strain-dependent manner

Human norovirus is the leading cause of gastroenteritis worldwide. Norovirus exhibits remarkable genetic diversity. Understanding the impact of genetic diversity on infection and immunity has been challenging due to the difficulties of in vitro cultivation and the current lack of a small animal model. Murine norovirus (MNV) has emerged as a premier model system to investigate norovirus biology. Here, we identify Trim47 as a host restriction factor that potently inhibits MNV infection in a strain dependent manner. We determine that Trim47 expression inhibits an early stage of the viral life cycle for the MNV strain CR6, while the replication of the closely related strain CW3 is not restricted by Trim47. Using a forward genetic screen we determine that genetic variation within the nonstructural gene NS1 accounts for this differential sensitivity to Trim47. While most TRIM containing proteins promote the ubiquitination and degradation of its targets, Trim47 does neither. Instead, Trim47 promotes the deubiquitination of the NS1/2 precursor protein. Our data provide new insight into a potential antiviral gene and mechanistic insight into norovirus evolution that may impact viral tropism. ImportanceViruses exist as genetically heterogeneous populations. Understanding the contribution of viral genetic variation on infection outcomes is critical in predicting emerging viruses and their variants. Noroviruses are genetically diverse but human norovirus has been technically challenging to study. In this study we use the model system murine norovirus to identify a viral strain specific restriction mechanism where a host gene can specifically restrict one strain of the virus but has no impact on a closely related strain. Dissecting the mechanism of this specificity provides insight into viral diversity and possible host restriction pathways.

microbiology↗

bioRxiv2025

Dynamics of Bacterial and Viral Transmission in Experimental Microbiota Transplantation

Mouse models are vital tools for discerning the relative contributions of host and microbial genetics to disease, often requiring the transplantation of microbiota between different mouse strains. Transfer methods include antibiotic treatment of recipients and colonization using either co-housing with donors or the transplantation of fecal or cecal donor material. However, the efficiency and dynamics of these methods in reconstituting recipients with donor microbes is not well understood. We thus directly compared co-housing, fecal transplantation, and cecal transplantation methods. Donor mice from Taconic Biosciences, possessing distinct microbial communities, served as the microbial source for recipient mice from Jackson Laboratories, which were treated with antibiotics to disrupt their native microbiota. We monitored bacterial and viral populations longitudinally over the course of antibiotics treatment and reconstitution using 16S rRNA gene sequencing, quantitative PCR, and shotgun sequencing of viral-like particles. As expected, antibiotic treatment rapidly depleted microbial biomass and diversity, with slow and incomplete natural recovery of the microbiota in non-transplanted control mice. While all transfer methods reconstituted recipient mice with donor microbiota, co-housing achieved this more rapidly for both bacterial and viral communities. This study provides valuable insights into microbial transfer methods, enhancing reproducibility and informing best practices for microbiota transplantation in mouse models.

microbiology↗