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

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

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

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 /

ZIKV infection regulates inflammasomes pathway for replication in monocytes

© 2017 The Author(s). ZIKV causes microcephaly by crossing the placental barrier, however, the mechanism of trans-placental dissemination of ZIKV remains unknown. Here, we sought to determine whether monocytes, which can cross tissue barriers, assist ZIKV dissemination to the fetus. We determined this by infecting monocytes with two strains of ZIKV: South American (PRVABC59) and Nigerian (IBH30656) and analyzing viral replication. We found that ZIKV infects and replicates in monocytes and macrophages, which results in the modulation of a large number of cellular genes. Analysis of these genes identified multiple pathways including inflammasome to be targeted by ZIKV, which was confirmed by analyzing the transcript levels of the proteins of inflammasome pathways, NLRP3, ASC, caspase 1, IL-1 and IL-18. Interestingly, IFNα and the IFN inducible gene, MxA were not enhanced, suggesting prevention of innate antiviral defense by ZIKV. Also, inhibition of inflammasome led to an increased transcriptional activity of IFNα, MxA and CXCL10. Based on these results we suggest that ZIKV transcription is regulated by inflammasomes

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

Serum cytokine profiles differentiating hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome

© 2017 Khaiboullina, Levis, Morzunov, Martynova, Anokhin, Gusev, St Jeor, Lombardi and Rizvanov.Hantavirus infection is an acute zoonosis that clinically manifests in two primary forms, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). HFRS is endemic in Europe and Russia, where the mild form of the disease is prevalent in the Tatarstan region. HPS is endemic in Argentina, as well as other countries of North and South American. HFRS and HPS are usually acquired via the upper respiratory tract by inhalation of virus-contaminated aerosol. Although the pathogenesis of HFRS and HPS remains largely unknown, postmortem tissue studies have identified endothelial cells as the primary target of infection. Importantly, cell damage due to virus replication, or subsequent tissue repair, has not been documented. Since no single factor has been identified that explains the complexity of HFRS or HPS pathogenesis, it has been suggested that a cytokine storm may play a crucial role in the manifestation of both diseases. In order to identify potential serological markers that distinguish HFRS and HPS, serum samples collected during early and late phases of the disease were analyzed for 48 analytes using multiplex magnetic bead-based assays. Overall, serum cytokine profiles associated with HPS revealed a more pro-inflammatory milieu as compared to HFRS. Furthermore, HPS was strictly characterized by the upregulation of cytokine levels, in contrast to HFRS where cases were distinguished by a dichotomy in serum cytokine levels. The severe form of hantavirus zoonosis, HPS, was characterized by the upregulation of a higher number of cytokines than HFRS (40 vs 21). In general, our analysis indicates that, although HPS and HFRS share many characteristic features, there are distinct cytokine profiles for these diseases. These profiles suggest a strong activation of an innate immune and inflammatory responses are associated with HPS, relative to HFRS, as well as a robust activation of Th1-type immune responses. Finally, the results of our analysis suggest that serum cytokines profiles of HPS and HFRS cases are consistent with the presence of extracellular matrix degradation, increased mononuclear leukocyte proliferation, and transendothelial migration