TMEM106B-mediated SARS-CoV-2 infection allows for robust ACE2-independent infection in vitro but not in vivo.

Angiotensin-converting enzyme 2 (ACE2) is the primary entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but ACE2-independent entry has been observed in vitro for strains with the spike-E484D substitution. Here, we conduct a whole-genome CRISPR-Cas9 knockout screen using SARS-CoV-2 mouse adapted 1 (SARS-CoV-2), which carries spike-E484D, to identify the ACE2-independent entry mechanisms. SARS-CoV-2 infection in HEK293T cells relies on heparan sulfate and endocytic pathways, with TMEM106B, a transmembrane lysosomal protein, the most significant contributor.

The effects of iron deficient and high iron diets on SARS-CoV-2 lung infection and disease.

Introduction: The severity of Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often dictated by a range of comorbidities. A considerable literature suggests iron deficiency and iron overload may contribute to increased infection, inflammation and disease severity, although direct causal relationships have been difficult to establish.

Methods: Here we generate iron deficient and iron loaded C57BL/6 J mice by feeding standard low and high iron diets, with mice on a normal iron diet representing controls.

Safety concern of recombination between self-amplifying mRNA vaccines and viruses is mitigated in vivo.

Self-amplifying mRNA (SAM) vaccines can be rapidly deployed in the event of disease outbreaks. A legitimate safety concern is the potential for recombination between alphavirus-based SAM vaccines and circulating viruses. This theoretical risk needs to be assessed in the regulatory process for SAM vaccine approval.

SARS-CoV-2 omicron BA.5 and XBB variants have increased neurotropic potential over BA.1 in K18-hACE2 mice and human brain organoids.

The reduced pathogenicity of the omicron BA.1 sub-lineage compared to earlier variants is well described, although whether such attenuation is retained for later variants like BA.5 and XBB remains controversial.

Use of Antibiotics to Eliminate Wolbachia from Mosquitoes and Cell Culture.

Removal of Wolbachia from infected insects is required in most experimental settings when the effects of Wolbachia on biological traits, pathogen blocking, reproduction, and fitness are assessed. This is to ensure that the genetic backgrounds of Wolbachia-infected and uninfected insects are the same. Here, we describe methodologies used for the elimination of Wolbachia from insects and insect cell lines with antibiotics.

Chikungunya patient transcriptional signatures faithfully recapitulated in a C57BL/6J mouse model.

Introduction: An adult wild-type C57BL/6J mouse model of chikungunya virus (CHIKV) infection and disease has been extensively used to study the alphaviral arthritic immunopathology and to evaluate new interventions. How well mouse models recapitulate the gene expression profiles seen in humans remains controversial.

Methods: Herein we perform a comparative transcriptomics analysis using RNA-Seq datasets from the C57BL/6J CHIKV mouse model with datasets obtained from adults and children acutely infected with CHIKV.

Warmer ambient air temperatures reduce nasal turbinate and brain infection, but increase lung inflammation in the K18-hACE2 mouse model of COVID-19.

Warmer climatic conditions have been associated with fewer COVID-19 cases. Herein we infected K18-hACE2 mice housed at the standard animal house temperature of ∼22 °C, or at ∼31 °C, which is considered to be thermoneutral for mice. On day 2 post infection, RNA-Seq analyses showed no significant differential gene expression lung in lungs of mice housed at the two temperatures, with almost identical viral loads and type I interferon responses.

Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression.

How well mouse models recapitulate the transcriptional profiles seen in humans remains debatable, with both conservation and diversity identified in various settings. Herein we use RNA-Seq data and bioinformatics approaches to analyze the transcriptional responses in SARS-CoV-2 infected lungs, comparing 4 human studies with the widely used K18-hACE2 mouse model, a model where hACE2 is expressed from the mouse ACE2 promoter, and a model that uses a mouse adapted virus and wild-type mice. Overlap of single copy orthologue differentially expressed genes (scoDEGs) between human and mouse studies was generally poor (≈15-35%).

Analysis of Aedes aegypti microRNAs in response to Wolbachia wAlbB infection and their potential role in mosquito longevity.

The mosquito Aedes aegypti is the primary vector of a range of medically important viruses including dengue, Zika, West Nile, yellow fever, and chikungunya viruses. The endosymbiotic bacterium Wolbachia pipientis wAlbB strain is a promising biocontrol agent for blocking viral transmission by Ae. aegypti.

Evolution of ACE2-independent SARS-CoV-2 infection and mouse adaption after passage in cells expressing human and mouse ACE2.

Human Human angiotensin converting enzyme 2 (hACE2) is the key cell attachment and entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the original SARS-CoV-2 isolates unable to use mouse (mACE2). Herein we describe the emergence of a SARS-CoV-2 strain capable of -independent infection and the evolution of mouse-adapted (MA) SARS-CoV-2 by serial passaging of virus in co-cultures of cell lines expressing hACE2 and mACE2. MA viruses evolved with up to five amino acid changes in the spike protein, all of which have been seen in human isolates.

Next Steps: Applying a Trauma-Informed Model to Create an Anti-Racist Organizational Culture.

Although there has been a significant increase in the delivery of evidence-supported, trauma-informed care over the past few years, there has been less discussion around the consideration of the broader cultural, political, and societal factors that contextualize client trauma and that also need to be recognized and understood to promote healing and prevent future trauma. In support of sharing some best practices and lessons learned, this article provides a case study of one agency that has used the Sanctuary Model, an evidence-supported, trauma-informed organizational change model, to introduce the practice of cultural humility with staff as a facilitator of improved service delivery for clients from culturally marginalized communities. The model supports these endeavors through the adherence to the seven commitments, a set of organizational values for creating a trauma-informed community, allowing for all voices to be heard and considered and providing opportunities to begin the repair of previous experiences of inequity and suppression.

Microplastic consumption induces inflammatory signatures in the colon and prolongs a viral arthritis.

Global microplastic (MP) contamination and the effects on the environment are well described. However, the potential for MP consumption to affect human health remains controversial. Mice consuming ≈80 μg/kg/day of 1 μm polystyrene MPs via their drinking water showed no weight loss, nor were MPs detected in internal organs.

ACE2-lentiviral transduction enables mouse SARS-CoV-2 infection and mapping of receptor interactions.

SARS-CoV-2 uses the human ACE2 (hACE2) receptor for cell attachment and entry, with mouse ACE2 (mACE2) unable to support infection. Herein we describe an ACE2-lentivirus system and illustrate its utility for in vitro and in vivo SARS-CoV-2 infection models. Transduction of non-permissive cell lines with hACE2 imparted replication competence, and transduction with mACE2 containing N30D, N31K, F83Y and H353K substitutions, to match hACE2, rescued SARS-CoV-2 replication.

Transcriptional Response of to Dengue Virus Infection in Cells of the Mosquito Aedes aegypti.

Aedes aegypti transmits one of the most significant mosquito-borne viruses, dengue virus (DENV). The absence of effective vaccines and clinical treatments and the emergence of insecticide resistance in A. aegypti necessitate novel vector control strategies.

BET inhibition blocks inflammation-induced cardiac dysfunction and SARS-CoV-2 infection.

Cardiac injury and dysfunction occur in COVID-19 patients and increase the risk of mortality. Causes are ill defined but could be through direct cardiac infection and/or inflammation-induced dysfunction. To identify mechanisms and cardio-protective drugs, we use a state-of-the-art pipeline combining human cardiac organoids with phosphoproteomics and single nuclei RNA sequencing.

Altered gene expression profile of Wolbachia pipientis wAlbB strain following transinfection from its native host Aedes albopictus to Aedes aegypti cells.

Wolbachia is an obligate intracellular bacterial symbiont prevalent among arthropods and nematodes. To survive and reproduce, Wolbachia interacts with and modifies host subcellular structures, while sensing and responding to changes within the cellular environment. In mutualistic associations, Wolbachia may provision the host with metabolites, or help to maintain the chemical homeostasis of the host cell.

Effect of AlbB on a positive-sense RNA negev-like virus: a novel virus persistently infecting mosquitoes and cells.

The mosquito is the primary vector of several medically important arboviruses. The endosymbiotic bacterium, , has emerged as a means of blocking transmission of arboviruses such as dengue and Zika viruses. One strain that has shown potential in field trials is AlbB, a naturally occurring strain of the Asian tiger mosquito .

Density-dependent enhanced replication of a densovirus in Wolbachia-infected Aedes cells is associated with production of piRNAs and higher virus-derived siRNAs.

The endosymbiotic bacterium Wolbachia pipientis has been shown to restrict a range of RNA viruses in Drosophila melanogaster and transinfected dengue mosquito, Aedes aegypti. Here, we show that Wolbachia infection enhances replication of Aedes albopictus densovirus (AalDNV-1), a single stranded DNA virus, in Aedes cell lines in a density-dependent manner. Analysis of previously produced small RNAs of Aag2 cells showed that Wolbachia-infected cells produced greater absolute abundance of virus-derived short interfering RNAs compared to uninfected cells.