Remote sensing and geographic information systems: charting Sin Nombre virus infections in deer mice.

We tested environmental data from remote sensing and geographic information system maps as indicators of Sin Nombre virus (SNV) infections in deer mouse (Peromyscus maniculatus) populations in the Walker River Basin, Nevada and California. We determined by serologic testing the presence of SNV infections in deer mice from 144 field sites. We used remote sensing and geographic information systems data to characterize the vegetation type and density, elevation, slope, and hydrologic features of each site. The data retroactively predicted infection status of deer mice with up to 80% accuracy. If models of SNV temporal dynamics can be integrated with baseline spatial models, human risk for infection may be assessed with reasonable accuracy

DNA Vaccine-Generated Duck Polyclonal Antibodies as a Postexposure Prophylactic to Prevent Hantavirus Pulmonary Syndrome (HPS)

Andes virus (ANDV) is the predominant cause of hantavirus pulmonary syndrome (HPS) in South America and the only hantavirus known to be transmitted person-to-person. There are no vaccines, prophylactics, or therapeutics to prevent or treat this highly pathogenic disease (case-fatality 35–40%). Infection of Syrian hamsters with ANDV results in a disease that closely mimics human HPS in incubation time, symptoms of respiratory distress, and disease pathology. Here, we evaluated the feasibility of two postexposure prophylaxis strategies in the ANDV/hamster lethal disease model. First, we evaluated a natural product, human polyclonal antibody, obtained as fresh frozen plasma (FFP) from a HPS survivor. Second, we used DNA vaccine technology to manufacture a polyclonal immunoglobulin-based product that could be purified from the eggs of vaccinated ducks (Anas platyrhynchos). The natural “despeciation" of the duck IgY (i.e., Fc removed) results in an immunoglobulin predicted to be minimally reactogenic in humans. Administration of ≥5,000 neutralizing antibody units (NAU)/kg of FFP-protected hamsters from lethal disease when given up to 8 days after intranasal ANDV challenge. IgY/IgYΔFc antibodies purified from the eggs of DNA-vaccinated ducks effectively neutralized ANDV in vitro as measured by plaque reduction neutralization tests (PRNT). Administration of 12,000 NAU/kg of duck egg-derived IgY/IgYΔFc protected hamsters when administered up to 8 days after intranasal challenge and 5 days after intramuscular challenge. These experiments demonstrate that convalescent FFP shows promise as a postexposure HPS prophylactic. Moreover, these data demonstrate the feasibility of using DNA vaccine technology coupled with the duck/egg system to manufacture a product that could supplement or replace FFP. The DNA vaccine-duck/egg system can be scaled as needed and obviates the necessity of using limited blood products obtained from a small number of HPS survivors. This is the first report demonstrating the in vivo efficacy of any antiviral product produced using DNA vaccine-duck/egg system

Pro-HEART — A randomized clinical trial to test the effectiveness of a high protein diet targeting obese individuals with heart failure: Rationale, design and baseline characteristics

There is ample research to support the potential benefits of a high protein diet on clinical outcomes in overweight/obese, diabetic subjects. However, nutritional management of overweight/obese individuals with heart failure (HF) and type 2 diabetes mellitus (DM) or metabolic syndrome (MS) is poorly understood and few clinical guidelines related to nutritional approaches exist for this subgroup. This article describes the design, methods, and baseline characteristics of study participants enrolled in Pro-HEART, a randomized clinical trial to determine the short term and long term effects of a high protein diet (30% protein [~110 g/day], 40% carbohydrates [150 g/day], 30% fat [~50 g/day]) versus a standard protein diet (15% protein [~55 g/day], 55% carbohydrates [~200 g/day], 30% fat [~50 g/day]) on body weight and adiposity, cardiac structure and function, functional status, lipid profile, glycemic control, and quality of life. Between August, 2009 and May, 2013, 61 individuals agreed to participate in the study; 52 (85%) - mean age 58.2 ± 9.8 years; 15.4% Blacks; 57.7% Whites; 19.2% Hispanics; 7.7% Asians; 73.1% male; weight 112.0 ± 22.6 kilograms- were randomized to a 3-month intensive weight management program of either a high protein or standard protein diet; data were collected at baseline, 3 months, and 15 months. This study has the potential to reveal significant details about the role of macronutrients in weight management of overweight/obese individuals with HF and DM or MS

Dietary factors impact on the association between CTSS variants and obesity related traits.

Cathepsin S, a protein coded by the CTSS gene, is implicated in adipose tissue biology--this protein enhances adipose tissue development. Our hypothesis is that common variants in CTSS play a role in body weight regulation and in the development of obesity and that these effects are influenced by dietary factors--increased by high protein, glycemic index and energy diets

Sin Nombre Virus and Rodent Species Diversity: A Test of the Dilution and Amplification Hypotheses

BACKGROUND:Species diversity is proposed to greatly impact the prevalence of pathogens. Two predominant hypotheses, the "Dilution Effect" and the "Amplification Effect", predict divergent outcomes with respect to the impact of species diversity. The Dilution Effect predicts that pathogen prevalence will be negatively correlated with increased species diversity, while the Amplification Effect predicts that pathogen prevalence will be positively correlated with diversity. For many host-pathogen systems, the relationship between diversity and pathogen prevalence has not be empirically examined. METHODOLOGY/PRINCIPAL FINDINGS:We tested the Dilution and Amplification Effect hypotheses by examining the prevalence of Sin Nombre virus (SNV) with respect to diversity of the nocturnal rodent community. SNV is directly transmitted primarily between deer mice (Peromyscus maniculatus). Using mark-recapture sampling in the Spring and Fall of 2003-2005, we measured SNV prevalence in deer mice at 16 landscape level sites (3.1 hectares each) that varied in rodent species diversity. We explored several mechanisms by which species diversity may affect SNV prevalence, including reduced host density, reduced host persistence, the presence of secondary reservoirs and community composition. We found a negative relationship between species diversity and SNV prevalence in deer mice, thereby supporting the Dilution Effect hypothesis. Deer mouse density and persistence were lower at sites with greater species diversity; however, only deer mouse persistence was positively correlated with SNV prevalence. Pinyon mice (P. truei) may serve as dilution agents, having a negative effect on prevalence, while kangaroo rats (Dipodomys ordii), may have a positive effect on the prevalence of SNV, perhaps through effects on deer mouse behavior. CONCLUSIONS/SIGNIFICANCE:While previous studies on host-pathogen systems have found patterns of diversity consistent with either the Dilution or Amplification Effects, the mechanisms by which species diversity influences prevalence have not been investigated. Our study indicates that changes in host persistence, coupled with interspecific interactions, are important mechanisms through which diversity may influence patterns of pathogens. Our results reveal the complexity of rodent community interactions with respect to SNV dynamics

Modulation of Human Mesenchymal Stem Cell Immunogenicity through Forced Expression of Human Cytomegalovirus US Proteins

BACKGROUND: Mesenchymal stem cells (MSC) are promising candidates for cell therapy, as they migrate to areas of injury, differentiate into a broad range of specialized cells, and have immunomodulatory properties. However, MSC are not invisible to the recipient's immune system, and upon in vivo administration, allogeneic MSC are able to trigger immune responses, resulting in rejection of the transplanted cells, precluding their full therapeutic potential. Human cytomegalovirus (HCMV) has developed several strategies to evade cytotoxic T lymphocyte (CTL) and Natural Killer (NK) cell recognition. Our goal is to exploit HCMV immunological evasion strategies to reduce MSC immunogenicity. METHODOLOGY/PRINCIPAL FINDINGS: We genetically engineered human MSC to express HCMV proteins known to downregulate HLA-I expression, and investigated whether modified MSC were protected from CTL and NK attack. Flow cytometric analysis showed that amongst the US proteins tested, US6 and US11 efficiently reduced MSC HLA-I expression, and mixed lymphocyte reaction demonstrated a corresponding decrease in human and sheep mononuclear cell proliferation. NK killing assays showed that the decrease in HLA-I expression did not result in increased NK cytotoxicity, and that at certain NK∶MSC ratios, US11 conferred protection from NK cytotoxic effects. Transplantation of MSC-US6 or MSC-US11 into pre-immune fetal sheep resulted in increased liver engraftment when compared to control MSC, as demonstrated by qPCR and immunofluorescence analyses. CONCLUSIONS AND SIGNIFICANCE: These data demonstrate that engineering MSC to express US6 and US11 can be used as a means of decreasing recognition of MSC by the immune system, allowing higher levels of engraftment in an allogeneic transplantation setting. Since one of the major factors responsible for the failure of allogeneic-donor MSC to engraft is the mismatch of HLA-I molecules between the donor and the recipient, MSC-US6 and MSC-US11 could constitute an off-the-shelf product to overcome donor-recipient HLA-I mismatch