Deanna Larson - Academia.edu (original) (raw)
Papers by Deanna Larson
The prevalence of the Omicron subvariant BA.2.75 is rapidly increasing in India and Nepal. In add... more The prevalence of the Omicron subvariant BA.2.75 is rapidly increasing in India and Nepal. In addition, BA.2.75 has been detected in at least 34 other countries and is spreading globally. However, the virological features of BA.2.75 are largely unknown. Here, we evaluated the replicative ability and pathogenicity of BA.2.75 clinical isolates in Syrian hamsters. Although we found no substantial differences in weight change among hamsters infected with BA.2, BA.5, or BA.2.75, the replicative ability of BA.2.75 in the lungs was higher than that of BA.2 and BA.5. Of note, BA.2.75 caused focal viral pneumonia in hamsters, characterized by patchy inflammation interspersed in alveolar regions, which was not observed in BA.5-infected hamsters. Moreover, in competition assays, BA.2.75 replicated better than BA.5 in the lungs of hamsters. These results suggest that BA.2.75 can cause more severe respiratory disease than BA.5 and BA.2 and should be closely monitored.
The BA.2 sublineage of the SARS-CoV-2 Omicron variant has become dominant in most countries aroun... more The BA.2 sublineage of the SARS-CoV-2 Omicron variant has become dominant in most countries around the world; however, the prevalence of BA.4 and BA.5 is increasing rapidly in several regions. BA.2 is less pathogenic in animal models than previously circulating variants of concern (VOC). Compared with BA.2, however, BA.4 and BA.5 possess additional substitutions in the spike protein, which play a key role in viral infectivity, raising concerns that the infectivity and pathogenicity of BA.4 and BA.5 are higher than those of BA.2. Here, we evaluated the replicative ability and pathogenicity of authentic BA.4 and BA.5 isolates in wild-type Syrian hamsters and human ACE2 (hACE2) transgenic hamsters. In contrast to recent data with a recombinant chimeric virus possessing the spike protein of BA.4/BA.5 in the background of a BA.2 strain, we observed no obvious differences among BA.2, BA.4, and BA.5 isolates in growth ability or pathogenicity in hamsters, and less pathogenicity compared to...
The FASEB Journal, 2016
The cherry fruit is a nutrient‐dense food with comparatively low caloric content and significant ... more The cherry fruit is a nutrient‐dense food with comparatively low caloric content and significant amounts of key nutrients and bioactive food chemicals. Much of the health benefit of cherries is attributed to their high amounts of anthocyanins, which have anti‐oxidant and anti‐cancer properties that contribute to changes in cell signaling pathways involved in inflammation, carcinogenesis and angiogenesis. In this project, we aimed to determine whether dietary supplementation with tart cherries prevents colon tumor development in mice consuming a Western diet compared to a prudent diet. Previously, our research team developed the Total Western Diet (TWD) for mice to emulate typical U.S. nutrition with respect to macro‐ (sugars, fats, and protein) and micronutrient (vitamin and mineral) contents (Hintze, et al. 2012 J Ag Food Chem 60(27): 6736–6742). Incorporating the TWD in pre‐clinical studies allows for the analysis of the impact of dietary bioactives or functional foods on tumor de...
The recent emergence of SARS-CoV-2 Omicron variants possessing large numbers of mutations has rai... more The recent emergence of SARS-CoV-2 Omicron variants possessing large numbers of mutations has raised concerns of decreased effectiveness of current vaccines, therapeutic monoclonal antibodies, and antiviral drugs for COVID-19 against these variants1,2. While the original Omicron lineage, BA.1, has become dominant in many countries, BA.2 has been detected in at least 67 countries and has become dominant in the Philippines, India, and Denmark. Here, we evaluated the replicative ability and pathogenicity of an authentic infectious BA.2 isolate in immunocompetent and human ACE2 (hACE2)-expressing mice and hamsters. In contrast to recent data with chimeric, recombinant SARS-CoV-2 strains expressing the spike proteins of BA.1 and BA.2 on an ancestral WK-521 backbone3, we observed similar infectivity and pathogenicity in mice and hamsters between BA.2 and BA.1, and less pathogenicity compared to early SARS-CoV-2 strains. We also observed a marked and significant reduction in the neutralizi...
The FASEB Journal, 2015
Our research team developed a new total Western diet (TWD) for rodents that mimics typical human ... more Our research team developed a new total Western diet (TWD) for rodents that mimics typical human nutrition patterns with respect to macronutrient composition (amounts and types of sugar, fat, prote...
Nature, 2022
The recent emergence of B.1.1.529, the Omicron variant1,2, has raised concerns of escape from pro... more The recent emergence of B.1.1.529, the Omicron variant1,2, has raised concerns of escape from protection by vaccines and therapeutic antibodies. A key test for potential countermeasures against B.1.1.529 is their activity in preclinical rodent models of respiratory tract disease. Here, using the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme of the National Institute of Allergy and Infectious Diseases (NIAID), we evaluated the ability of several B.1.1.529 isolates to cause infection and disease in immunocompetent and human ACE2 (hACE2)-expressing mice and hamsters. Despite modelling data indicating that B.1.1.529 spike can bind more avidly to mouse ACE2 (refs. 3,4), we observed less infection by B.1.1.529 in 129, C57BL/6, BALB/c and K18-hACE2 transgenic mice than by previous SARS-CoV-2 variants, with limited weight loss and lower viral burden in the upper and lower respiratory tracts. In wild-type and hACE2 transgenic hamsters, lung infection,...
mBio, 2022
The rapid emergence of SARS-CoV-2 has created a global health emergency. While most human SARS-Co... more The rapid emergence of SARS-CoV-2 has created a global health emergency. While most human SARS-CoV-2 disease is mild, some people develop severe, life-threatening disease.
Despite the development and deployment of antibody and vaccine countermeasures, rapidly-spreading... more Despite the development and deployment of antibody and vaccine countermeasures, rapidly-spreading SARS-CoV-2 variants with mutations at key antigenic sites in the spike protein jeopardize their efficacy. The recent emergence of B.1.1.529, the Omicron variant1,2, which has more than 30 mutations in the spike protein, has raised concerns for escape from protection by vaccines and therapeutic antibodies. A key test for potential countermeasures against B.1.1.529 is their activity in pre-clinical rodent models of respiratory tract disease. Here, using the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) program of the National Institute of Allergy and Infectious Diseases (NIAID), we evaluated the ability of multiple B.1.1.529 Omicron isolates to cause infection and disease in immunocompetent and human ACE2 (hACE2) expressing mice and hamsters. Despite modeling and binding data suggesting that B.1.1.529 spike can bind more avidly to murine ACE2, we observed at...
The FASEB Journal, 2015
Previously, we showed that both the total dietary PUFA concentration and the ratio of n3 and n6 P... more Previously, we showed that both the total dietary PUFA concentration and the ratio of n3 and n6 PUFA affected systemic inflammation when mice were challenged with lipopolysaccharide. Therefore, we ...
The majority of colorectal cancer cases can be attributed to poor diet, yet Americans routinely c... more The majority of colorectal cancer cases can be attributed to poor diet, yet Americans routinely consume highly processed foods that are energy- dense and nutrient-poor. The primary objective of this study was to determine the impact of ancestral or multi-generational exposure to the total Western diet (TWD), a Western-style diet formulated for rodents using human US nutrient intake data, in a murine model of inflammation-associated colorectal carcinogenesis. The hypotheses tested were 1) consumption of TWD by F0 parents would promote colitis-associated colorectal cancer (CAC) in F3 generation offspring and 2) consumption of TWD over multiple generations would further exacerbate disease development compared to direct-exposed offspring. C57BL/6J mice were bred for three generations, during which they were fed a standard diet (AIN93G), TWD, or a simple high fat diet (DIO, 45% diet-induced obesity diet) during the F0 generation only, for the duration of F0 through F3 generations, or the F3 generation only. The azoxymethane and dextran sodium sulfate model of CAC was employed in F3 offspring, which were necropsied at 24 weeks of age. Notably, tumor incidence was increased by trans-generational exposure to TWD (92%) when compared to consecutive AIN93G exposure only (56%). Moreover, successive exposure to TWD markedly increased tumor burden (\u3e 3-fold increase) when compared to direct TWD exposure. Alternatively, neither trans-generational nor multi-generational exposure to DIO altered tumor incidence; however, tumor burden was unexpectedly increased in F3 offspring trans-generationally-exposed to the DIO was observed as compared to direct DIO exposure. In summary, ancestral exposure to TWD markedly increased CAC incidence and disease severity in third generation offspring that were not directly fed this diet. Additionally, continuous exposure to TWD over three generations exacerbated disease outcome in third generation offspring as compared to those fed TWD directly
Nutrients, 2020
Background: Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite,... more Background: Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. We sought to determine: (1) TMAO response to meals containing free versus lipid-soluble choline and (2) effects of gut microbiome on TMAO response. Methods: In a randomized, controlled, double-blinded, crossover study, healthy men (n = 37) were provided meals containing 600 mg choline either as choline bitartrate or phosphatidylcholine, or no choline control. Results: Choline bitartrate yielded three-times greater plasma TMAO AUC (p = 0.01) and 2.5-times greater urinary TMAO change from baseline (p = 0.01) compared to no choline and phosphatidylcholine. Gut microbiota composition differed (permutational multivariate analysis of variance, PERMANOVA; p = 0.01) between high-TMAO producers (with ≥40% increase in urinary TMAO response to choline bitartrate) and low-TMAO producers (with <40% increase in TMAO response). High-TMAO...
Current Developments in Nutrition, 2020
Objectives Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, ... more Objectives Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. However, the contributions of different forms of choline and gut microbiota composition on TMAO production are largely unknown. The objectives of this study were to: 1) compare acute TMAO response to meals containing free choline (choline bitartrate) versus fat-soluble choline (phosphatidylcholine) and 2) to determine the effects of gut microbiota composition on TMAO response. Methods In a controlled, double-blinded, cross-over study, healthy men (n = 37) were provided meals containing (i) 600 mg choline as choline bitartrate (free choline); (ii) 600 mg choline as phosphatidylcholine; or (iii) no choline control in a random order. Blood and urine samples were collected at baseline and throughout the 6-h study period; a one-time stool sample was collected at baseline. Results Compared to no choline and phosphatidylcholine, free...
Journal of Animal Science, 2016
Virology Journal, 2013
Background Tacaribe virus (TCRV) is a less biohazardous relative of the highly pathogenic clade B... more Background Tacaribe virus (TCRV) is a less biohazardous relative of the highly pathogenic clade B New World arenaviruses that cause viral hemorrhagic fever syndromes and require handling in maximum containment facilities not readily available to most researchers. AG129 type I and II interferon receptor knockout mice have been shown to be susceptible to TCRV infection, but the pathogenic mechanisms contributing to the lethal disease are unclear. Methods To gain insights into the pathogenesis of TCRV infection in AG129 mice, we assessed hematologic and cytokine responses during the course of infection, as well as changes in the permeability of the vascular endothelium. We also treated TCRV-challenged mice with MY-24, a compound that prevents mortality without affecting viral loads during the acute infection, and measured serum and tissue viral titers out to 40 days post-infection to determine whether the virus is ultimately cleared in recovering mice. Results We found that the develop...
The prevalence of the Omicron subvariant BA.2.75 is rapidly increasing in India and Nepal. In add... more The prevalence of the Omicron subvariant BA.2.75 is rapidly increasing in India and Nepal. In addition, BA.2.75 has been detected in at least 34 other countries and is spreading globally. However, the virological features of BA.2.75 are largely unknown. Here, we evaluated the replicative ability and pathogenicity of BA.2.75 clinical isolates in Syrian hamsters. Although we found no substantial differences in weight change among hamsters infected with BA.2, BA.5, or BA.2.75, the replicative ability of BA.2.75 in the lungs was higher than that of BA.2 and BA.5. Of note, BA.2.75 caused focal viral pneumonia in hamsters, characterized by patchy inflammation interspersed in alveolar regions, which was not observed in BA.5-infected hamsters. Moreover, in competition assays, BA.2.75 replicated better than BA.5 in the lungs of hamsters. These results suggest that BA.2.75 can cause more severe respiratory disease than BA.5 and BA.2 and should be closely monitored.
The BA.2 sublineage of the SARS-CoV-2 Omicron variant has become dominant in most countries aroun... more The BA.2 sublineage of the SARS-CoV-2 Omicron variant has become dominant in most countries around the world; however, the prevalence of BA.4 and BA.5 is increasing rapidly in several regions. BA.2 is less pathogenic in animal models than previously circulating variants of concern (VOC). Compared with BA.2, however, BA.4 and BA.5 possess additional substitutions in the spike protein, which play a key role in viral infectivity, raising concerns that the infectivity and pathogenicity of BA.4 and BA.5 are higher than those of BA.2. Here, we evaluated the replicative ability and pathogenicity of authentic BA.4 and BA.5 isolates in wild-type Syrian hamsters and human ACE2 (hACE2) transgenic hamsters. In contrast to recent data with a recombinant chimeric virus possessing the spike protein of BA.4/BA.5 in the background of a BA.2 strain, we observed no obvious differences among BA.2, BA.4, and BA.5 isolates in growth ability or pathogenicity in hamsters, and less pathogenicity compared to...
The FASEB Journal, 2016
The cherry fruit is a nutrient‐dense food with comparatively low caloric content and significant ... more The cherry fruit is a nutrient‐dense food with comparatively low caloric content and significant amounts of key nutrients and bioactive food chemicals. Much of the health benefit of cherries is attributed to their high amounts of anthocyanins, which have anti‐oxidant and anti‐cancer properties that contribute to changes in cell signaling pathways involved in inflammation, carcinogenesis and angiogenesis. In this project, we aimed to determine whether dietary supplementation with tart cherries prevents colon tumor development in mice consuming a Western diet compared to a prudent diet. Previously, our research team developed the Total Western Diet (TWD) for mice to emulate typical U.S. nutrition with respect to macro‐ (sugars, fats, and protein) and micronutrient (vitamin and mineral) contents (Hintze, et al. 2012 J Ag Food Chem 60(27): 6736–6742). Incorporating the TWD in pre‐clinical studies allows for the analysis of the impact of dietary bioactives or functional foods on tumor de...
The recent emergence of SARS-CoV-2 Omicron variants possessing large numbers of mutations has rai... more The recent emergence of SARS-CoV-2 Omicron variants possessing large numbers of mutations has raised concerns of decreased effectiveness of current vaccines, therapeutic monoclonal antibodies, and antiviral drugs for COVID-19 against these variants1,2. While the original Omicron lineage, BA.1, has become dominant in many countries, BA.2 has been detected in at least 67 countries and has become dominant in the Philippines, India, and Denmark. Here, we evaluated the replicative ability and pathogenicity of an authentic infectious BA.2 isolate in immunocompetent and human ACE2 (hACE2)-expressing mice and hamsters. In contrast to recent data with chimeric, recombinant SARS-CoV-2 strains expressing the spike proteins of BA.1 and BA.2 on an ancestral WK-521 backbone3, we observed similar infectivity and pathogenicity in mice and hamsters between BA.2 and BA.1, and less pathogenicity compared to early SARS-CoV-2 strains. We also observed a marked and significant reduction in the neutralizi...
The FASEB Journal, 2015
Our research team developed a new total Western diet (TWD) for rodents that mimics typical human ... more Our research team developed a new total Western diet (TWD) for rodents that mimics typical human nutrition patterns with respect to macronutrient composition (amounts and types of sugar, fat, prote...
Nature, 2022
The recent emergence of B.1.1.529, the Omicron variant1,2, has raised concerns of escape from pro... more The recent emergence of B.1.1.529, the Omicron variant1,2, has raised concerns of escape from protection by vaccines and therapeutic antibodies. A key test for potential countermeasures against B.1.1.529 is their activity in preclinical rodent models of respiratory tract disease. Here, using the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme of the National Institute of Allergy and Infectious Diseases (NIAID), we evaluated the ability of several B.1.1.529 isolates to cause infection and disease in immunocompetent and human ACE2 (hACE2)-expressing mice and hamsters. Despite modelling data indicating that B.1.1.529 spike can bind more avidly to mouse ACE2 (refs. 3,4), we observed less infection by B.1.1.529 in 129, C57BL/6, BALB/c and K18-hACE2 transgenic mice than by previous SARS-CoV-2 variants, with limited weight loss and lower viral burden in the upper and lower respiratory tracts. In wild-type and hACE2 transgenic hamsters, lung infection,...
mBio, 2022
The rapid emergence of SARS-CoV-2 has created a global health emergency. While most human SARS-Co... more The rapid emergence of SARS-CoV-2 has created a global health emergency. While most human SARS-CoV-2 disease is mild, some people develop severe, life-threatening disease.
Despite the development and deployment of antibody and vaccine countermeasures, rapidly-spreading... more Despite the development and deployment of antibody and vaccine countermeasures, rapidly-spreading SARS-CoV-2 variants with mutations at key antigenic sites in the spike protein jeopardize their efficacy. The recent emergence of B.1.1.529, the Omicron variant1,2, which has more than 30 mutations in the spike protein, has raised concerns for escape from protection by vaccines and therapeutic antibodies. A key test for potential countermeasures against B.1.1.529 is their activity in pre-clinical rodent models of respiratory tract disease. Here, using the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) program of the National Institute of Allergy and Infectious Diseases (NIAID), we evaluated the ability of multiple B.1.1.529 Omicron isolates to cause infection and disease in immunocompetent and human ACE2 (hACE2) expressing mice and hamsters. Despite modeling and binding data suggesting that B.1.1.529 spike can bind more avidly to murine ACE2, we observed at...
The FASEB Journal, 2015
Previously, we showed that both the total dietary PUFA concentration and the ratio of n3 and n6 P... more Previously, we showed that both the total dietary PUFA concentration and the ratio of n3 and n6 PUFA affected systemic inflammation when mice were challenged with lipopolysaccharide. Therefore, we ...
The majority of colorectal cancer cases can be attributed to poor diet, yet Americans routinely c... more The majority of colorectal cancer cases can be attributed to poor diet, yet Americans routinely consume highly processed foods that are energy- dense and nutrient-poor. The primary objective of this study was to determine the impact of ancestral or multi-generational exposure to the total Western diet (TWD), a Western-style diet formulated for rodents using human US nutrient intake data, in a murine model of inflammation-associated colorectal carcinogenesis. The hypotheses tested were 1) consumption of TWD by F0 parents would promote colitis-associated colorectal cancer (CAC) in F3 generation offspring and 2) consumption of TWD over multiple generations would further exacerbate disease development compared to direct-exposed offspring. C57BL/6J mice were bred for three generations, during which they were fed a standard diet (AIN93G), TWD, or a simple high fat diet (DIO, 45% diet-induced obesity diet) during the F0 generation only, for the duration of F0 through F3 generations, or the F3 generation only. The azoxymethane and dextran sodium sulfate model of CAC was employed in F3 offspring, which were necropsied at 24 weeks of age. Notably, tumor incidence was increased by trans-generational exposure to TWD (92%) when compared to consecutive AIN93G exposure only (56%). Moreover, successive exposure to TWD markedly increased tumor burden (\u3e 3-fold increase) when compared to direct TWD exposure. Alternatively, neither trans-generational nor multi-generational exposure to DIO altered tumor incidence; however, tumor burden was unexpectedly increased in F3 offspring trans-generationally-exposed to the DIO was observed as compared to direct DIO exposure. In summary, ancestral exposure to TWD markedly increased CAC incidence and disease severity in third generation offspring that were not directly fed this diet. Additionally, continuous exposure to TWD over three generations exacerbated disease outcome in third generation offspring as compared to those fed TWD directly
Nutrients, 2020
Background: Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite,... more Background: Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. We sought to determine: (1) TMAO response to meals containing free versus lipid-soluble choline and (2) effects of gut microbiome on TMAO response. Methods: In a randomized, controlled, double-blinded, crossover study, healthy men (n = 37) were provided meals containing 600 mg choline either as choline bitartrate or phosphatidylcholine, or no choline control. Results: Choline bitartrate yielded three-times greater plasma TMAO AUC (p = 0.01) and 2.5-times greater urinary TMAO change from baseline (p = 0.01) compared to no choline and phosphatidylcholine. Gut microbiota composition differed (permutational multivariate analysis of variance, PERMANOVA; p = 0.01) between high-TMAO producers (with ≥40% increase in urinary TMAO response to choline bitartrate) and low-TMAO producers (with <40% increase in TMAO response). High-TMAO...
Current Developments in Nutrition, 2020
Objectives Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, ... more Objectives Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. However, the contributions of different forms of choline and gut microbiota composition on TMAO production are largely unknown. The objectives of this study were to: 1) compare acute TMAO response to meals containing free choline (choline bitartrate) versus fat-soluble choline (phosphatidylcholine) and 2) to determine the effects of gut microbiota composition on TMAO response. Methods In a controlled, double-blinded, cross-over study, healthy men (n = 37) were provided meals containing (i) 600 mg choline as choline bitartrate (free choline); (ii) 600 mg choline as phosphatidylcholine; or (iii) no choline control in a random order. Blood and urine samples were collected at baseline and throughout the 6-h study period; a one-time stool sample was collected at baseline. Results Compared to no choline and phosphatidylcholine, free...
Journal of Animal Science, 2016
Virology Journal, 2013
Background Tacaribe virus (TCRV) is a less biohazardous relative of the highly pathogenic clade B... more Background Tacaribe virus (TCRV) is a less biohazardous relative of the highly pathogenic clade B New World arenaviruses that cause viral hemorrhagic fever syndromes and require handling in maximum containment facilities not readily available to most researchers. AG129 type I and II interferon receptor knockout mice have been shown to be susceptible to TCRV infection, but the pathogenic mechanisms contributing to the lethal disease are unclear. Methods To gain insights into the pathogenesis of TCRV infection in AG129 mice, we assessed hematologic and cytokine responses during the course of infection, as well as changes in the permeability of the vascular endothelium. We also treated TCRV-challenged mice with MY-24, a compound that prevents mortality without affecting viral loads during the acute infection, and measured serum and tissue viral titers out to 40 days post-infection to determine whether the virus is ultimately cleared in recovering mice. Results We found that the develop...