Biology subjects

Petkova, S.

Publications and source records attributed to Petkova, S..

3 recordsLinked to original sources

bioRxiv2024

Rhesus Cytomegalovirus-encoded Fcγ-binding glycoproteins facilitate viral evasion from IgG-mediated humoral immunity

Human cytomegalovirus (HCMV) encodes four viral Fc-gamma receptors (vFc{gamma}Rs) that counteract antibody-mediated activation in vitro, but their role in infection and pathogenesis is unknown. To examine the in vivo function of vFc{gamma}Rs in animal hosts closely related to humans, we identified and characterized vFc{gamma}Rs encoded by rhesus CMV (RhCMV). We demonstrate that Rh05, Rh152/151 and Rh173 represent the complete set of RhCMV vFc{gamma}Rs, each displaying functional similarities to their respective HCMV orthologs with respect to antagonizing host Fc{gamma}R activation in vitro. When RhCMV-naive rhesus macaques were infected with vFc{gamma}R-deleted RhCMV, peak plasma viremia levels and anti-RhCMV antibody responses were comparable to wildtype infections. However, the duration of plasma viremia was significantly shortened in immunocompetent, but not in CD4+ T cell-depleted animals. Since vFc{gamma}Rs were not required for superinfection, we conclude that vFc{gamma}Rs delay control by virus-specific adaptive immune responses, particularly antibodies, during primary infection.

microbiology↗

bioRxiv2021

Insulin-like growth factor-2 does not improve behavioral deficits in mouse and rat models of Angelman Syndrome

BackgroundAngelman Syndrome (AS) is a rare neurodevelopmental disorder for which there is currently no cure or effective therapeutic. Since the genetic cause of AS is known to be dysfunctional expression of the maternal allele of ubiquitin protein ligase E3A (UBE3A), several genetic animal models of AS have been developed. Both the Ube3a maternal deletion mouse and rat models of AS reliably demonstrate behavioral phenotypes of relevance to AS and therefore offer suitable in vivo systems in which to test potential therapeutics. One promising candidate treatment is insulin-like growth factor-2 (IGF-2), which has recently been shown to ameliorate behavioral deficits in the mouse model of AS and improve cognitive abilities across model systems. MethodsWe used both the Ube3a maternal deletion mouse and rat models of AS to evaluate the ability of IGF-2 to improve electrophysiological and behavioral outcomes. ResultsAcute systemic administration of IGF-2 had an effect on electrophysiological activity in the brain and on a metric of motor ability, however the effects were not enduring or extensive. Additional metrics of motor behavior, learning, ambulation, and coordination were unaffected and IGF-2 did not improve social communication, seizure threshold, or cognition. LimitationsThe generalizability of these results to humans is difficult to predict and it remains possible that dosing schemes (i.e., chronic or subchronic dosing), routes, and/or post-treatment intervals other than that used herein may show more efficacy. ConclusionsDespite a few observed effects of IGF-2, our results taken together indicate that IGF-2 treatment does not profoundly improve behavioral deficits in mice or rat models of AS. These findings shed cautionary light on the potential utility of acute systemic IGF-2 administration in the treatment of AS.

pharmacology and toxicology↗

bioRxiv2020

Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance

Oxytocin increases the salience of both positive and negative social contexts and it is thought that these diverse actions on behavior are mediated in part through circuit-specific action. This hypothesis is based primarily on manipulations of oxytocin receptor function, leaving open the question of whether different populations of oxytocin neurons mediate different effects on behavior. Here we inhibited oxytocin synthesis in a social stress-sensitive population of oxytocin neurons specifically within the medioventral bed nucleus of the stria terminalis (BNSTmv). Oxytocin knock-down prevented stress-induced increases in social vigilance and decreases in social approach. Viral tracing of BNSTmv oxytocin neurons revealed fibers in regions controlling defensive behaviors including lateral hypothalamus, anterior hypothalamus, and anteromedial BNST (BNSTam). Oxytocin infusion into BNSTam in stress naive mice increased social vigilance and reduced social approach. These results show that a population of extra-hypothalamic oxytocin neurons play a key role in controlling stress-induced social anxiety behaviors.

neuroscience↗