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Botten, J.

Publications and source records attributed to Botten, J..

2 recordsLinked to original sources

Specific and versatile monoclonal antibodies for hantavirus research

Rodent-borne hantaviruses pose a continual public health threat to humans through zoonotic transmission, with case fatality rates of up to 50% in some cases. Human infections can lead to hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardio-pulmonary syndrome (HCPS), depending on the viral species. Despite the morbidity and mortality associated with this family of viruses, no anti-viral therapeutics or vaccines are available to treat and prevent hantavirus disease. The relative shortage of commercially available reagents to study hantavirus infections in vitro and in vivo likely contributes to the challenges in developing viral countermeasures. This report describes the generation of a panel of mouse monoclonal antibodies that collectively recognize the four viral proteins of Seoul virus (Orthohantavirus seoulense), an Old World hantavirus with worldwide distribution and the causative agent of HFRS. We have validated the specificity and versatility of these antibodies against a subset of Old World and New World hantaviruses in assays relying on antigen recognition in denatured or native conformations. We present several antibodies that specifically recognize the Seoul virus nucleoprotein and polymerase protein in Western blotting and immunostaining assays. We also identified three novel antibodies directed against the glycoprotein complex that are capable of binding to the N-terminal glycoprotein of all hantaviruses tested. These antibodies are freely available to all hantavirus researchers to add to the small, but growing, collection of reliable and available reagents to be used to study hantavirus biology, identify novel antiviral compounds, and measure viral prevalence in the laboratory and the field. ImportancePathogenic hantaviruses cause severe hemorrhagic disease and pose a significant public health threat world-wide. Insufficient research into the biology of these viruses has slowed the development of effective direct-acting antivirals and vaccines. Here, we describe the generation and validation of novel, specific monoclonal antibodies for the detection of Seoul virus proteins in vitro. These reagents can be used to fill in critical gaps in knowledge regarding hantavirus entry, protein expression, and particle generation.

microbiology↗

The Cellular Immunity Agent-Based Model (CIABM): A computational model to examine the role of cellular immunity in viral infection

Viral respiratory infections, such as influenza, result in over 1 million deaths worldwide each year. To date, there are few therapeutic interventions able to affect the course of the disease once acquired, a deficit with stark consequences that were readily evident in the current COVID-19 pandemic. We present the Cellular Immune Agent Based Model (CIABM) as a flexible framework for modeling acute viral infection and cellular immune memory development. The mechanism/rule-based nature of the CIABM allows for interrogation of the complex dynamics of the human immune system during various types of viral infections. The CIABM is an extension of a prior agent-based model of the innate immune response, incorporating additional cellular types and mediators involved in the response to viral infection. The CIABM simulates the dynamics of viral respiratory infection in terms of epithelial invasion, immune cellular population changes and cytokine measurements. Validation of the CIABM involved effectively replicating in vivo measurements of circulating mediator levels from a clinical cohort of influenza patients. The general purpose nature of the CIABM allows for both the representation of various types of known viral infections and facilitates the exploration of hypothetical, novel viral pathogens.

immunology↗