Life in the tundra

A creative thesis written for the nonfiction sequence of the Southern New Hampshire University Master of Fine Arts Creative Writing programMaster of Fine Arts (M.F.A.)School of Arts and Science

The structure of the hantavirus zinc finger domain is conserved and represents the only natively folded region of the Gn cytoplasmic tail

Hantaviruses, of the family Bunyaviridae, are present throughout the world and cause a variety of infections ranging from the asymptomatic to mild and severe hemorrhagic fevers. Hantaviruses are enveloped anti-sense RNA viruses that contain three genomic segments that encode for a nucleocapsid protein, two membrane glycoproteins (Gn and Gc), and an RNA polymerase. Recently, the pathogenicity of hantaviruses has been mapped to the carboxyl end of the 150 residue Gn cytoplasmic tail. The Gn tail has also been shown to play a role in binding the ribonucleoprotein (RNP), a step critical for virus assembly. In this study, we use NMR spectroscopy to compare the structure of a Gn tail zinc finger domain of both a pathogenic (Andes) and a non-pathogenic (Prospect Hill) hantavirus. We demonstrate that despite a stark difference in the virulence of both of these viruses, the structure of the Gn core zinc finger domain is largely conserved in both strains. We also use NMR backbone relaxation studies to demonstrate that the regions of the Andes virus Gn tail immediately outside the zinc finger domain, sites known to bind the RNP, are disordered and flexible, thus intimating that the zinc finger domain is the only structured region of the Gn tail. These structural observations provide further insight into the role of the Gn tail during viral assembly as well as its role in pathogenesis

Hantavirus infection suppresses thrombospondin-1 expression in cultured endothelial cells in a strain-specific manner

© 2016 Khaiboullina, Morzunov, St. Jeor, Rizvanov and Lombardi.Hantavirus infection is associated with two frequently fatal diseases in humans: Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). The pathogenesis of hantavirus infection is complex and not fully understood; however, it is believed to involve virus-induced hyperinflammatory immune responses. Thrombospondin-1 (THBS1) is a large homotrimeric protein that plays a putative role in regulating blood homeostasis. Hyperresponsiveness to inflammatory stimuli has also been associated with defects in the THBS1 gene. Our data suggest that hantavirus infection of human umbilical cord vein endothelial cells (HUVEC) suppress the accumulation of THBS1 in the extracellular matrix. Additionally, this suppression is dependent on virus replication, implying a direct mechanism of action. Our data also imply that the pathogenic Andes and Hantaan strains inhibit THBS1 expression while the non-pathogenic Prospect Hill strain showed little inhibition. These observations suggest that a dysregulation of THBS1 may contribute to the pathogenesis of hantavirus infection

Multiplex analysis of serum cytokines in humans with hantavirus pulmonary syndrome

© 2015 Morzunov, Khaiboullina, St. Jeor, Rizvanov and Lombardi. Hantavirus pulmonary syndrome (HPS) is an acute zoonotic disease transmitted primarily through inhalation of virus-contaminated aerosols. Hantavirus infection of endothelial cells leads to increased vascular permeability without a visible cytopathic effect. For this reason, it has been suggested that the pathogenesis of HPS is indirect with immune responses, such as cytokine production, playing a dominant role. In order to investigate their potential contribution to HPS pathogenesis, we analyzed the serum of hantavirus-infected subjects and healthy controls for 68 different cytokines, chemokines, angiogenic, and growth factors. Our analysis identified differential expression of cytokines that promote tissue migration of mononuclear cells including T lymphocytes, natural killer cells, and dendritic cells. Additionally, we observed a significant upregulation of cytokines known to regulate leukocyte migration and subsequent repair of lung tissue, as well as cytokines known to increase endothelial monolayer permeability and facilitate leukocyte transendothelial migration. Conversely, we observed a downregulation of cytokines associated with platelet numbers and function, consistent with the thrombocytopenia observed in subjects with HPS. This study corroborates clinical findings and extends our current knowledge regarding immunological and laboratory findings in subjects with HPS

Who does not gain weight? Prevalence and predictors of weight maintenance in young women

OBJECTIVE: To investigate the prevalence and predictors of weight maintenance over time in a large sample of young Australian women. DESIGN: This population study examined baseline and 4 y follow-up data from the cohort of young women participating in the Australian Longitudinal Study on Women\u27s Health. SUBJECTS: A total of 8726 young women aged 18-23 y at baseline. MEASURES: Height, weight and body mass index (BMI); physical activity; time spent sitting; selected eating behaviours (eg dieting, disordered eating, takeaway food consumption); cigarette smoking, alcohol consumption; parity; and sociodemographic characteristics. RESULTS: Only 44% of the women reported their BMI at follow-up to be within 5% of their baseline BMI (maintainers); 41% had gained weight and 15% had lost weight. Weight maintainers were more likely to be in managerial or professional occupations; to have never married; to be currently studying; and not to be mothers. Controlling for sociodemographic factors, weight maintainers were more likely to be in a healthy weight range at baseline, and to report that they spent less time sitting, and consumed less takeaway food, than women who gained weight. CONCLUSIONS: Fewer than half the young women in this community sample maintained their weight over this 4 y period in their early twenties. Findings of widespread weight gain, particularly among those already overweight, suggest that early adulthood, which is a time of significant life changes for many women, may be an important time for implementing strategies to promote maintenance of healthy weight. Strategies which encourage decreased sitting time and less takeaway food consumption may be effective for encouraging weight maintenance at this life stage.<br /

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

Death-domain associated protein-6 (DAXX) mediated apoptosis in hantavirus infection is counter-balanced by activation of interferon-stimulated nuclear transcription factors

Hantaviruses are negative strand RNA species that replicate predominantly in the cytoplasm. They also activate numerous cellular responses, but their involvement in nuclear processes is yet to be established. Using human umbilical vein endothelial cells (HUVECs), this study investigates the molecular finger-print of nuclear transcription factors during hantavirus infection. The viral-replication-dependent activation of pro-myelocytic leukemia protein (PML) was followed by subsequent localization in nuclear bodies (NBs). PML was also found in close proximity to activated Sp100 nuclear antigen and interferon-stimulated gene 20. kDa protein (ISG-20), but co-localization with death-domain associated protein-6 (DAXX) was not observed. These data demonstrate that hantavirus triggers PML activation and localization in NBs in the absence of DAXX-PLM-NB co-localization. The results suggest that viral infection interferes with DAXX-mediated apoptosis, and expression of interferon-activated Sp100 and ISG-20 proteins may indicate intracellular intrinsic antiviral attempts. © 2013

Andes-virus-induced cytokine storm is partially suppressed by ribavirin

Background: Microbe-induced over-activation of cytokines, especially tumour necrosis factor (TNF)-α, is key to the pathogenesis of hantavirus infection leading to severe inflammation with high mortality rate. Although ribavirin showed promise in inhibiting viral replication in vitro, its clinical efficacy remains controversial. Methods: Various concentrations of ribavirin were used to determine its effect on cytokine activation in our infectious model system. Results: Ribavirin decreased the virus load and dosedependently inhibited the accumulation of RANTES messenger RNA in Andes-virus (ANDV)-infected human endothelial cells, but failed to suppress TNF-α-induced activation of RANTES and interleukin-6 in ANDV-inoculated cultures. This report also shows, for the first time, that the deleterious over-stimulation by TNF-α is mediated by nuclear factor-kB, and describes the effect of ribavirin on cytokine production following ANDV infection. Conclusions: Although highly effective in preventing ANDV replication and suppressing activation of select inflammatory mediators, the therapeutic efficacy of ribavirin is limited due to its inability to fully inhibit cytokine outburst triggered by hantavirus infection. © 2013 International Medical Press