Biology subjects

Bowen, J. M.

Publications and source records attributed to Bowen, J. M..

4 recordsLinked to original sources

bioRxiv2026

Reverse genetics and comparative pathogenesis of Lone star virus.

Lone star virus (LSV) is a bandavirus first isolated from Amblyomma americanum ticks in the United States (U.S.) and is phylogenetically related to severe fever with thrombocytopenia syndrome virus (SFTSV), Heartland virus (HRTV), and Bhanja virus, each of which has been associated with severe human disease. In contrast to these better-characterized bandaviruses, LSV remains poorly studied, and its pathogenic potential is not well defined. Recent detection of LSV RNA in cerebrospinal fluid from an immunocompromised patient in Idaho, U.S., with fatal meningoencephalitis further highlights the need for experimental systems to investigate LSV biology. Here, we rescued recombinant (r) LSV from cloned cDNA and used it to characterize LSV. rLSV replicated similarly to the parental isolate in mammalian cells and caused rapid, systemic, and lethal disease in IFNAR-/- mice, with widespread detection of viral (v) RNA across multiple tissues, hepatic and splenic pathology, and induction of inflammatory cytokines. In contrast, C57BL/6J mice controlled infection and exhibited no clinical disease. To place LSV within a broader comparative framework, we generated rSFTSV from cloned cDNA and compared rLSV, rSFTSV, and HRTV in cell culture and IFNAR-/- mice. Our studies revealed distinct disease kinetics among these related tick-borne bandaviruses and showed that HRTV-induced immunity protected against homologous HRTV rechallenge and heterologous rSFTSV challenge, but not rLSV challenge. Together, these findings establish reverse-genetics platforms and small-animal models for comparative bandavirus studies, define key features of LSV pathogenesis, and place this neglected virus within a framework of related bandaviruses that differ in virulence and immunological overlap. ImportanceTick-borne bandaviruses include several viruses associated with severe human disease, yet many related viruses remain poorly characterized. Lone star virus (LSV) was first isolated from Amblyomma americanum ticks decades ago, but experimental tools and animal models to study LSV infection have been lacking. Here, we generated a recombinant LSV and used it to define the outcome of infection in immunocompromised and immunocompetent mice. We show that LSV can cause rapid, systemic, and lethal disease when type I interferon signaling is absent, whereas immunocompetent mice restrict infection and remain clinically normal. By comparing LSV with Heartland virus and severe fever with thrombocytopenia syndrome virus, we also show that related tick-borne bandaviruses differ in disease kinetics and immune protection. These findings provide foundational tools for studying LSV and highlight the importance of experimentally characterizing neglected tick-borne viruses before their pathogenic potential is fully understood.

microbiology↗

bioRxiv2025

From prototype to outbreak: conserved pathogenesis of Oropouche virus in a novel murine pregnancy model highlights its public health implications

Oropouche virus (OROV) is an emerging orthobunyavirus responsible for widespread outbreaks across South and Central America. The recent surge in congenital infections has raised urgent concerns about OROVs threat to maternal and fetal health. Here, we establish an in vivo model of OROV vertical transmission using the ancestral (prototype) strain BeAn19991 in immunocompetent C57BL/6J mice. We demonstrate that OROV efficiently replicates in maternal tissues, crosses the maternal-fetal interface, and infects both placental and fetal tissues. Parallel infections in human trophoblast-derived cell lines confirm conserved placental tropism across the ancestral strain and a contemporary (outbreak) isolate from the current outbreak. Importantly, we show that vertical transmission is not a recently acquired trait but a long-standing feature of OROV biology. Offspring born to infected dams mount neutralizing antibody responses and exhibit partial protection upon challenge. These findings conclusively confirm OROV as a vertically transmissible arbovirus, highlighting the urgent need to integrate OROV into surveillance, diagnostic, and vaccine preparedness efforts.

microbiology↗

bioRxiv2024

Type-2 diabetes mellitus enhances Klebsiella pneumoniae pathogenesis

Klebsiella pneumoniae is an opportunistic pathogen and an important cause of pneumonia, bacteremia, and urinary tract infection. K. pneumoniae infections are historically associated with diabetes mellitus. There is a fundamental gap in our understanding of how diabetes mellitus, specifically type 2 diabetes, influences K. pneumoniae pathogenesis. K. pneumoniae pathogenesis is a multifactorial process that often begins with gut colonization, followed by an escape from the gut to peripheral sites, leading to host damage and infection. We hypothesized that type 2 diabetes enhances K. pneumoniae pathogenesis. To test this, we used well-established mouse models of K. pneumoniae colonization and lung infection in conjunction with a mouse model of spontaneous type 2 diabetes mellitus (T2DM). We show that T2DM enhances susceptibility to both K. pneumoniae colonization and infection. The enhancement of gut colonization is dependent on T2DM-induced modulation of the gut microbiota community structure. In contrast, lung infection is exacerbated by the increased availability of amino acids in the lung, which is associated with higher levels of vascular endothelial growth factor. These data lay the foundation for mechanistic interrogation of the relationship between K. pneumoniae pathogenesis and type 2 diabetes mellitus, and explicitly establish T2DM as a risk factor for K. pneumoniae disease.

microbiology↗

bioRxiv2019

TLR4 mediates Il-6 production in irinotecan induced mucositis

IntroductionIrinotecan is a first line chemotherapeutic agent for colorectal carcinoma and well known for debilitating diarrhoea caused by mucositis. Tlr4, a pattern recognition receptor, has been implicated in irinotecan -induced mucositis due to its activation of downstream inflammatory pathways and interaction with luminal microbes. Tlr4 deletion has been reported to attenuate mucosal injury in preclinical models of mucositis, hypothesised to occur by blockade of Il-6 production. As such, the current study aimed to determine the relationship between Tlr4 and Il-6 in the context of irinotecan induced mucositis.\n\nMaterials and methodsArchived ileum and colon tissues from BALB/c wild type (WT) and Tlr4 -/-billy (Tlr4 KO) female mice were used throughout the study. Mice had received single dose of irinotecan (i.p. 270 mg/kg) or vehicle and sacrificed at 6 and 72 hours. Il-6 mRNA and protein expression was determined by qPCR and immunofluorescence, respectively. Data was analysed by Kruskal-Wallis test (qPCR delta CT values) and one-way analysis of variance (ANOVA) (immunofluorescence % area stained).\n\nResultsIl-6 protein expression was significantly reduced in Tlr4 KO mice as compared to WT mice at 6 h in ileum and colon. mRNA expression was not significantly different between groups.\n\nConclusionThese findings support the hypothesis that Tlr4 deletion protects from irinotecan-induced mucositis by ameliorating Il-6 production. The effect appears to be post-transcriptionally mediated, although further research is required to determine if it is via a direct or indirect mechanism. In the future, Il-6 may be targeted therapeutically to ameliorate symptoms of mucositis.

physiology↗