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Stacy, C. L.

Publications and source records attributed to Stacy, C. L..

2 recordsLinked to original sources

Quantifying relative virulence: When μmax fails and AUC alone just isn't enough

AO_SCPLOWBSTRACTC_SCPLOWOne of the more challenging aspects in quantitative virology is quantifying relative virulence between two (or more) viruses that have different replication dynamics in a given susceptible host. Host growth curve analysis is often used to detail virus-host interactions and to determine the impact of viral infection on a host. Quantifying relative virulence using canonical parameters such as maximum specific growth rate (max) can fail to provide accurate information regarding experimental infection, especially for non-lytic viruses. Although area-under-the-curve (AUC) can be more robust by through calculation of a percent inhibition (PIAUC), this metric can be sensitive to limit selection. In this study, using empirical and extrapolated data from Sulfolobus Spindle-shaped Virus (SSV) infections, we introduce a novel, simple metric that is proven to be more robust and less sensitive than traditional measures for determining relative virulence. This metric (ISC) more accurately aligns biological phenomena with quantified metrics from growth curve analysis to determine trends in relative virulence. It also addresses a major gap in virology by allowing comparisons between non-lytic single-virus/single-host (SVSH) infections and between non-lytic versus lytic virus infection on a given host. How ISC may be applied to polymicrobial infection - both coinfection of a host culture and superinfection of a single cell with more than one virus (or other pathogen type) is a topic of ongoing investigation.

microbiology

Host-dependent differences in replication strategy of the Sulfolobus Spindle-shaped Virus strain SSV9 (a.k.a., SSVK1): Lytic replication in hosts of the family Sulfolobaceae

The Sulfolobus Spindle-shaped Virus (SSV) system has become a model for studying thermophilic virus biology, including archaeal host-virus interactions and biogeography. Several factors make the SSV system amenable to studying archaeal genetic mechanisms (e.g., CRISPRs) as well as virus-host interactions in high temperature acidic environments. First, it has been shown that endemic populations of Sulfolobus, the reported SSV host, exhibit biogeographic structure. Second, the acidic (pH<4.5) high temperature (65-88{degrees}C) SSV habitats have low biodiversity, thus, diminishing opportunities for host switching. Third, SSVs and their hosts are readily cultured in liquid media and on gellan gum plates. Fourth, given the wide geographic separation between the various SSV-Sulfolobus habitats, the system is amenable for studying allopatric versus sympatric virus-host interactions. Previously, we reported that SSVs exhibit differential infectivity on allopatric and sympatric hosts. We also noticed a wide host range for virus strain SSV9 (a.k.a., SSVK1). For decades, SSVs have been described as "non-lytic" dsDNA viruses that infect species of the genus Sulfolobus and release virions via "blebbing" or "budding" as a preferred strategy over host lysis. Here, we show that SSVs infect more than one genus of the family Sulfolobaceae and, in allopatric hosts, SSV9 does not appear to release virions by blebbing. Instead, SSV9 appears to lyse all susceptible allopatric hosts tested, while exhibiting canonical non-lytic viral release via "blebbing" (historically reported for all other SSVs), on a single sympatric host. Lytic versus non-lytic virion release does not appear to be driven by multiplicity of infection (MOI). Greater relative stability of SSV9 compared to other SSVs (i.e., SSV1) in high temperature, low pH environments may contribute to higher transmission rates. However, neither higher transmission rate nor relative virulence in SSV9 infection drives replication profile (i.e., lytic versus non-lytic) in susceptible hosts. Although it is known that CRISPR-Cas systems offer protection against viral infection in prokaryotes, CRISPRS are not reported to be a determinant virus replication strategy. Thus, the genetic/molecular mechanisms underlying SSV9-induced lysis are unknown. These results suggest that there are unknown genetic elements, resulting from allopatric evolution, that drive virion release strategy in specific host strain-SSV strain pairings.

microbiology