Browsing by Subject "Enterovirus"
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Item Entero viruses(1958-09-09) UnknownItem Factors That Influence Murine Norovirus Stability and Tropism(2024-05) Budicini, Melissa Renee; Gammon, Don B.; Schoggins, John W.; Pfeiffer, Julie K.; Orchard, Robert C.In this work I investigated factors that influence murine norovirus stability and tropism through two independent projects. Murine norovirus (MNV) is a model system used to study human noroviruses due to its robust replication in cell culture and mouse model. I first investigated the interactions between MNV and bacteria in vitro by determining what bacteria and bacterial components could impact viral thermostability. I found that that specific Gram-positive bacteria and conditioned medium from Gram-positive bacteria could stabilize MNV against heat inactivation. However, I found that Gram-negative bacteria and conditioned medium had no impact on viral stability. These stabilizing effects of bacteria may play a role in viral transmission due to the fact that the virus must remain stable in the environment to transmit to a new host. In my second project I used a forward genetic approach to select for MNV variants with increased host cell range. I found that by serially passaging murine norovirus in human HeLa cells I could select for mutant viruses that increased replication as compared with the parental strain in a non-natural host. The passaged viruses had many mutations spanning the viral genome, however I determined three specific mutations in the NS1/2 protein that allowed for the virus to grow better in human cells. I determined that the adapted viruses have increased replication because they overcame a post-entry replication block in HeLa cells, not because they have increased attachment. This was surprising given that HeLa cells do not have the MNV receptor. These studies show that MNV tropism is not only determined by receptor availability. Overall, these studies illuminate unique aspects of MNV biology that may be applicable to other viruses.Item Unique Aspects of Intestinal Biology That Influence Enteric Virus Infection(2021-05-01T05:00:00.000Z) Woods Acevedo, Mikal Aaron; Orchard, Robert C.; Pfeiffer, Julie K.; Schoggins, John W.; Winter, Sebastian E.Enteric viruses are human pathogens that pose a significant global health problem. In this work, I explore how unique facets of host biology influence enteric virus infection, ranging from intestinal microbiota to circadian rhythms. To examine these factors, I used coxsackievirus B3 (CVB3) and poliovirus, which serve as a powerful model viruses to understand virus-host interactions. CVB3 and poliovirus are nonenveloped single-stranded positive-sense RNA viruses, which spread through the fecal-oral route. While many enteric virus infections are mild, some can be severe or even fatal. Thus it is important to study which factors impact enteric virus infection. Throughout my dissertation I used a variety of mouse models to answer a multitude of questions related to what factors influence enteric virus infection. To study the microbiota-mediated enhancement of CVB3 infection, I used different methods of antibiotic depletion in mice. We determined that two related enteric viruses, CVB3 and poliovirus, differ in their requirements of the microbiota. Furthermore, I studied the antiviral effects of antibiotics in vitro and in vivo and found that while antibiotics are not antiviral for CVB3 in cell culture, they are antiviral for CVB3 in a mouse model. Finally, by infecting mice at different times of day, we determined that host circadian rhythms influence enteric virus susceptibility. In conclusion, using model enteric viruses, such as CVB3 and poliovirus, I elucidated multiple unique aspects of host biology, ranging from microbiota to circadian rhythms, that influence viral replication and pathogenesis.