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Biology subjects

Petric, P. P.

Publications and source records attributed to Petric, P. P..

2 recordsLinked to original sources
bioRxiv2022

Cold-passaged isolates and bat-swine influenza A chimeric viruses as modified live-attenuated vaccines against influenza A viruses in pigs

Swine influenza A virus (swIAV) infections in pig populations cause considerable morbidity and economic losses. Frequent reverse zoonotic incursions of human IAV boost reassortment opportunities with authentic porcine and avian-like IAV in swine herds potentially enhancing zoonotic and even pre-pandemic potential. Vaccination using adjuvanted inactivated full virus vaccines is frequently used in attempting control of swIAV infections. Accelerated antigenic drift of swIAV in large swine holdings and interference of maternal antibodies with vaccine in piglets can compromise these efforts. Potentially more efficacious modified live-attenuated vaccines (MLVs) bear the risk of reversion of MLV to virulence. Here we evaluated new MLV candidates based on cold-passaged swIAV or on reassortment-incompetent bat-IAV-swIAV chimeric viruses. Serial cold-passaging of various swIAV subtypes did not yield unambiguously temperature-sensitive mutants although safety studies in mice and pigs suggested some degree of attenuation. Chimeric bat-swIAV expressing the hemagglutinin and neuraminidase of an avian-like H1N1, in contrast, proved to be safe in mice and pigs, and a single nasal inoculation induced protective immunity against homologous challenge in pigs. Reassortant-incompetent chimeric bat-swIAV vaccines could aid in reducing the amount of swIAV circulating in pig populations, thereby increasing animal welfare, limiting economic losses and lowering the risk of zoonotic swIAV transmission.

microbiology↗
bioRxiv2021

Genome-Wide CRISPR Screening Identifies BRD9 as a Druggable Component of Interferon-Stimulated Gene Expression and Antiviral Activity

Transient interferon (IFN) induction of IFN-stimulated genes (ISGs) creates a formidable protective antiviral state. However, loss of appropriate control mechanisms can result in constitutive pathogenic ISG upregulation. Here, we used genome-wide loss-of-function screening to establish genes critical for IFN signaling, identifying all expected members of the JAK-STAT pathway and the previously unappreciated bromodomain-containing protein 9 (BRD9), a defining subunit of non-canonical BAF (ncBAF) chromatin remodeling complexes. Genetic knock-out or small-molecule mediated degradation of BRD9 limited IFN-induced expression of a subset of ISGs in multiple cell-types, and prevented IFN from exerting full antiviral activity against several RNA and DNA viruses. Mechanistically, BRD9 acts at the level of ISG transcription, exhibits a proximal association with STAT2 following IFN stimulation, and relies on its intact acetyl-binding bromodomain and unique ncBAF scaffolding function for activity. Given its druggability, BRD9 may be an attractive target for dampening constitutive ISG expression under certain pathogenic autoinflammatory conditions.

immunology↗