Relationship of oxygen tension to viral disease Final report
Tissue culture development for isolation and quantization of lymphocytic choriomeningitis virus
Kirk, B. E.↗
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Monkeys as a source of viral diseases in man
Under institutional scientific-research conditions, during contact with monkeys or their tissues, there is a danger of infection of the associates by simian viruses which are pathogenic to man. Presented in this paper is information on these stimulants.
Pille, E. R.↗
Evaluation of early recognition of viral infections in man
The potential of Lymphocyte Specific Gravity Distribution (LSGD) as a non-specific procedure for early diagnosis of viral disease in astronauts is considered. Results of experiments and a literature search show that several virus diseases result in distinctive changes in the specific gravity distribution of peripheral blood lymphocytes as a result of disease process and associated immune response. A tentative model is proposed which relates the shape of LSGD to the identity of subpopulations of peripheral lymphocytes in a preclinical viral disease situation.
Kelton, A. A.↗
Next Generation Respiratory Viral Vaccine System: Advanced and Emerging Bioengineered Human Lung Epithelia Model (HLEM) Organoid Technology
Acute respiratory infections, including pneumonia and influenza, are the S t" leading cause of United States and worldwide deaths. Newly emerging pathogens signaled the need for an advanced generation of vaccine technology.. Human bronchial-tracheal epithelial tissue was bioengineered to detect, identify, host and study the pathogenesis of acute respiratory viral disease. The 3-dimensional (3D) human lung epithelio-mesechymal tissue-like assemblies (HLEM TLAs) share characteristics with human respiratory epithelium: tight junctions, desmosomes, microvilli, functional markers villin, keratins and production of tissue mucin. Respiratory Syntial Virus (RSV) studies demonstrate viral growth kinetics and membrane bound glycoproteins up to day 20 post infection in the human lung-orgainoid infected cell system. Peak replication of RSV occurred on day 10 at 7 log10 particles forming units per ml/day. HLEM is an advanced virus vaccine model and biosentinel system for emergent viral infectious diseases to support DoD global surveillance and military readiness.
Goodwin, Thomas J.↗
Filovirus Research: The Need for an Integrated Approach in Time and Space
The episodic appearance of Ebola virus (EBOV) and Marburg virus (MARV) across central Africa over the last 15 years not only underscores the importance of filoviruses as uniquely virulent agents to both human and wildlife communities but also implies a very complex transmission scenario that must be understood if we are to prevent or mitigate filovirus outbreaks in the future. Efforts of a global network of scientists and healthcare workers have expanded our knowledge of filoviruses to meet the growing threat of Ebola and Marburg hemorrhagic fevers in Africa. In recent decades, several newly emerging diseases have resulted in major threats to both affected communities and global public health. Viruses from wildlife hosts in particular, have exhibited a capability for cross-species transmission (CST), and have caused high-impact diseases in humans Such as Ebola and Marburg hemorrhagic fevers, Nipah and severe acute respiratory syndrome (SAILS). It has been estimated that about 60.3% (Jones et al. 2008) of human infectious diseases are of animal origin (zoonoses) and even some important viral diseases that are traditionally considered of human origin, for example measles and smallpox, may very well have their prehistoric origins in wildlife (Wolfe et al 2007). It maybe logical and prudent therefore, to anticipate that there are other, new filoviruses out there that will cross into humans at some point in time. If we anticipate that these will happen and wish to be prepared for and mitigate this potential, then an understanding of filoviruses as a biologic system in the environment will be essential to that process. We will need to know how the ecological dynamic of CST interacts with a 'new' viruse's evolutionary factors to overcome environmental, demographic and host-specific barriers to transmission and infectivity to humans.
Pinzon, Jorge E.↗
Characteristics and tolerances of the pocket mouse and incidence of disease
Studies carried out on the pocket mouse colony on Apollo XVII are reported. They revealed no serological evidence of viral disease, no pathogenic enterobacteria or respiratory Mycoplasma on culture, a 25% incidence of sarcosporidiosis, and a 2% incidence of chronic meningitis or meningoencephalitis. It is concluded that the pocket mouse is a highly adaptive animal and very well-suited to space flight.
Lindberg, R. G.↗
Use of remote sensing for land use policy formulation
Multispectral scanning, infrared imagery, thematic mapping, and spectroradiometry from LANDSAT, GOES, and ground based instruments are being used to determine conifer distribution, maximum and minimum temperatures, topography, and crop diseases in Michigan's lower Peninsula. Image interpretation and automatic digital processing information from LANDSAT data are employed to classify and map the coniferous forests. Radiant temperature data from GOES were compared to temperature readings from the climatological station network. Digital data from LANDSAT is being used to develop techniques for detecting, monitoring, and modeling land surface change. Improved reflectance signatures through spectroradiometry aided in the detection of viral diseases in blueberry fields and vineyards. Soil survey maps from aerial reconnaissance are included as well as information on education, conferences, and awards.
Source record↗
Inactivation of a model coliphage virus in water by iodine
Until now, NASA's space water reuse research program has not considered the transport of water-borne infectious enteric viruses; however, viral diseases probably are a signifficant concern in long-duration space missions. To simplify monitoring and prediction of pathogen distribution, model indicator strains historically have been used. In this research, the male specific RNA coliphage MS-2 is used as a model of enteric viruses due to their similar size and biochemical composition. Inactivation of some water-borne enteric viruses by iodine has previously been characterized. In this paper, iodine inactivation of the model coliphage MS-2 in buffered water is compared with earlier bench-scale disinfection survival data and with survival in iodinated simulated shower water used in a test water recycling system.
Brion, Gail M.↗
Variations in Modeled Dengue Transmission over Puerto Rico Using a Climate Driven Dynamic Model
Dengue fever is a mosquito‐borne viral disease reemerging throughout much of the tropical Americas. Dengue virus transmission is explicitly influenced by climate and the environment through its primary vector, Aedes aegypti. Temperature regulates Ae. aegypti development, survival, and replication rates as well as the incubation period of the virus within the mosquito. Precipitation provides water for many of the preferred breeding habitats of the mosquito, including buckets, old tires, and other places water can collect. Because of variations in topography, ocean influences and atmospheric processes, temperature and rainfall patterns vary across Puerto Rico and so do dengue virus transmission rates. Using NASA's TRMM (Tropical Rainfall Measuring Mission) satellite for precipitation input, ground‐based observations for temperature input, and laboratory confirmed dengue cases reported by the Centers for Disease Control and Prevention for parameter calibration, we modeled dengue transmission at the county level across Puerto Rico from 2010‐2013 using a dynamic dengue transmission model that includes interacting vector ecology and epidemiological components. Employing a Monte Carlo approach, we performed ensembles of several thousands of model simulations for each county in order to resolve the model uncertainty arising from using different combinations of parameter values that are not well known. The top 1% of model simulations that best reproduced the reported dengue case data were then analyzed to determine the most important parameters for dengue virus transmission in each county, as well as the relative influence of climate variability on transmission. These results can be used by public health workers to implement dengue control methods that are targeted for specific locations and climate conditions.
Morin, Cory↗
Assessing Disparities of Dengue Virus Transmission Risk across the US-Mexican Border Using a Climate Driven Vector-Epidemiological Model
Dengue fever is a mosquito‐borne viral disease reemerging throughout much of the tropical Americas. Dengue virus transmission is explicitly influenced by climate and the environment through its primary vector, Aedes aegypti. Temperature regulates Ae. aegypti development, survival, and replication rates as well as the incubation period of the virus within the mosquito. Precipitation provides water for many of the preferred breeding habitats of the mosquito, including buckets, old tires, and other places water can collect. Although transmission regularly occurs along the border region in Mexico, dengue virus transmission in bordering Arizona has not occurred. Using NASA's TRMM (Tropical Rainfall Measuring Mission) satellite for precipitation input and Daymet for temperature and supplemental precipitation input, we modeled dengue transmission along a US‐Mexico transect using a dynamic dengue transmission model that includes interacting vector ecology and epidemiological components. Model runs were performed for 5 cities in Sonora, Mexico and southern Arizona. Employing a Monte Carlo approach, we performed ensembles of several thousands of model simulations in order to resolve the model uncertainty arising from using different combinations of parameter values that are not well known. For cities with reported dengue case data, the top model simulations that best reproduced dengue case numbers were retained and their parameter values were extracted for comparison. These parameter values were used to run simulations in areas where dengue virus transmission does not occur or where dengue fever case data was unavailable. Additional model runs were performed to reveal how changes in climate or parameter values could alter transmission risk along the transect. The relative influence of climate variability and model parameters on dengue virus transmission is assessed to help public health workers prepare location specific infection prevention strategies.
Morin, Cory↗
Modeling Influenza Transmission Using Environmental Parameters
Influenza is an acute viral respiratory disease that has significant mortality, morbidity and economic burden worldwide. It infects approximately 5-15% of the world population, and causes 250,000 500,000 deaths each year. The role of environments on influenza is often drawn upon the latitude variability of influenza seasonality pattern. In regions with temperate climate, influenza epidemics exhibit clear seasonal pattern that peak during winter months, but it is not as evident in the tropics. Toward this end, we developed mathematical model and forecasting capabilities for influenza in regions characterized by warm climate Hong Kong (China) and Maricopa County (Arizona, USA). The best model for Hong Kong uses Land Surface Temperature (LST), precipitation and relative humidity as its covariates. Whereas for Maricopa County, we found that weekly influenza cases can be best modelled using mean air temperature as its covariates. Our forecasts can further guides public health organizations in targeting influenza prevention and control measures such as vaccination.
Soebiyanto, Radina P.↗
Climate Models Go Viral: Simulating Climate and Environmentally Driven Infectious Diseases
No abstract available
Dengue↗
Infectious Disease Risk Associated with Space Flight
This slide presentation opens with views of the shuttle in various stages of preparation for launch, a few moments after launch prior to external fuel tank separation, a few pictures of the earth,and several pictures of astronomical interest. The presentation reviews the factors effecting the risks of infectious disease during space flight, such as the crew, water, food, air, surfaces and payloads and the factors that increase disease risk, the factors affecting the risk of infectious disease during spaceflight, and the environmental factors affecting immunity, such as stress. One factor in space infectious disease is latent viral reactivation, such as herpes. There are comparisons of the incidence of viral reactivation in space, and in other analogous situations (such as bed rest, or isolation). There is discussion of shingles, and the pain and results of treatment. There is a further discussion of the changes in microbial pathogen characteristics, using salmonella as an example of the increased virulence of microbes during spaceflight. A factor involved in the risk of infectious disease is stress.
Pierson, Duane L.↗
Paramyxovirus Infection Mimics In Vivo Cellular Dynamics in Three-Demensional Human Bronchio-Epithelial Tissue-Like Assemblies
Respiratory syncytial virus and parainfluenza virus cause severe respiratory disease, especially in infants, children and the elderly. An in vitro model that accurately mimics infection of the human respiratory epithelium (HRE) would facilitate vaccine development greatly. Monolayer cultures traditionally used to study these viruses do not accurately and precisely differentiate the replication efficiencies of wild type and attenuated viruses. Therefore, we engineered novel three-dimensional (3D) tissue-like assemblies (TLAs) of human broncho-epithelial (HBE) cells to produce a more physiologically relevant in vitro model of the HRE. TLAs resemble HRE structurally and by expression of differentiated epithelial cell markers. Most significantly, wild type viruses exhibited a clear growth advantage over attenuated strains in TLAs unlike monolayer cultures. In addition, the TLAs responded to virus infection by secreting pro-inflammatory mediators similar to the respiratory epithelia of infected children. These characteristics make the TLA model a valuable platform technology to develop and evaluate live, attenuated respiratory virus vaccine candidates for human use. Respiratory virus diseases, the most frequent and least preventable of all infectious diseases, range in severity from the common cold to severe bronchiolitis and pneumonia . Two paramyxoviruses, respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3), are responsible for a majority of the most severe respiratory diseases of infants and young children. RSV causes 70% of all bronchiolitis cases and is a major cause of morbidity and mortality worldwide, especially in infants. PIV3 causes 10-15% of bronchiolitis and pneumonia during infancy, second only to RSV, and 40% of croup in infants To date, licensed vaccines are not available to prevent these respiratory diseases. At present, traditional monkey kidney (Vero and LLC-MK2) and human (HEp-2) tissue culture cells and small animal models (mouse, cotton rat, guinea pig, ferret, and hamster) fail to accurately imitate viral replication and human disease states (8). Lacking an authentic model has impeded the development and evaluation of live, attenuated vaccine candidates. Development of a physiologically relevant in vitro tissue culture model that reproduces characteristics of the HRE, the primary target of RSV and PIV3, would aid in predicting clinical attenuation and safety of vaccine candidates. Successful tissue engineering of a 3D human intestinal model using novel NASA technology inspired the development of a tri-culture 3D model for the HRE. Sequential layering of primary mesenchymal cells (comprised of normal human fibroblasts and endothelial cells) followed by BEAS-2B epithelial cells derived from human bronchi and tracheae were recapitulated on Cultisphere and/or cytodex3 microcarriers in cylindrical vessels that rotate horizontally creating an organized epithelial structure. Horizontal rotation randomizes the gravity vector modeling aspects of microgravity. Mesenchymal and epithelial cells grown under these conditions reproduce the structural organization, multi-cellular complexity, and differentiation state of the HRE. The opportunity to study respiratory viruses in a nasal epithelium model is invaluable because the most promising respiratory virus vaccine candidates are live attenuated viruses for intranasal administration. Here we characterize the interactions of respiratory viruses and epithelial cells grown under modeled microgravity in comparison to gravity-ladened monolayers. 3D HBE TLAs and traditional monolayers (2D) are infected at 35 C, the upper temperature of the upper HRE, to simulate in vivo infection conditions. Growth kinetics of wild type (wt) RSV and PIV3 viruses were compared in 2D and 3D cells to that of strains attenuated in humans or rhesus macaques. This novel 3D HBE model also offers an opportunity to study whether the epithelial cell function, especially in host defenses recapitulated by mimicking the structural organization of the HRE. In vivo, airway epithelial cells play a significant and dynamic role in host defense by blocking paracellular permeability and modulating airway function through cellular interactions or tight junctions. As regulators of the innate immune response, epithelial cells constitutively express cytokines, chemokines, and colony stimulating factors including RANTES, IL-8, IL-6, GM-CSF, and G-CSF for proactive host defense. In response to viral infection, epithelial cells induce potent immuno-modulatory and pro-inflammatory cytokines that recruit phagocytic and inflammatory cells to clear the virus and enhance protection. Although disease pathogenesis is classically attributed to the cytopathic effects of the pathogen, severe disease states associated with RSV and PIV3 are attributed to the inflammatory response, especially in infants. RSV is a potent inducer of cytokines and pro-inflammatory mediators in epithelial cells in vivo. A differentiated human epithelial model independent of the complete functional immune system will help elucidate the role of epithelial cells in respiratory disease. We reported here, virus and host cell interactions in 3D HBE TLAs are similar to that in vivo. Because the epithelial cell organization of the TLAs impacts not only the expression of airway epithelial characteristics, but also cellular communication, the TLAs represent a more physiologically relevant model of the HRE than BEAS-2B or other non-tumour monolayer models of respiratory disease. As a result, wild type respiratory viruses have a clear growth advantage over attenuated viruses in TLAs unlike traditional monolayers. In addition, the TLAs respond to wild type virus infection by secreting pro-inflammatory mediators characteristic of infected HRE. TLAs expressing microbial defense mechanisms provide an excellent model to study the interactions of respiratory pathogens with their host and to identify the innate immunity mediators. Therefore, 3D HBE TLAs offer advantages for the study of respiratory viruses and the development of viral vaccine candidates.
Deatly, Anne M.↗
Viral carcinogenesis: revelation of molecular mechanisms and etiology of human disease
The RNA and DNA tumor viruses have made fundamental contributions to two major areas of cancer research. Viruses were vital, first, to the discovery and analysis of cellular growth control pathways and the synthesis of current concepts of cancer biology and, second, to the recognition of the etiology of some human cancers. Transforming retroviruses carry oncogenes derived from cellular genes that are involved in mitogenic signalling and growth control. DNA tumor viruses encode oncogenes of viral origin that are essential for viral replication and cell transformation; viral oncoproteins complex with cellular proteins to stimulate cell cycle progression and led to the discovery of tumor suppressors. Viral systems support the concept that cancer development occurs by the accumulation of multiple cooperating events. Viruses are now accepted as bona fide etiologic factors of human cancer; these include hepatitis B virus, Epstein-Barr virus, human papillomaviruses, human T-cell leukemia virus type I and hepatitis C virus, plus several candidate human cancer viruses. It is estimated that 15% of all human tumors worldwide are caused by viruses. The infectious nature of viruses distinguishes them from all other cancer-causing factors; tumor viruses establish long-term persistent infections in humans, with cancer an accidental side effect of viral replication strategies. Viruses are usually not complete carcinogens, and the known human cancer viruses display different roles in transformation. Many years may pass between initial infection and tumor appearance and most infected individuals do not develop cancer, although immunocompromised individuals are at elevated risk of viral-associated cancers. Variable factors that influence viral carcinogenesis are reviewed, including possible synergy between viruses and environmental cofactors. The difficulties in establishing an etiologic role for a virus in human cancer are discussed, as well as the different approaches that proved viral links to cancer. Future directions for tumor virus studies are considered.
NASA Program Biomedical Research and Countermeasur↗
Development of Machine Learning-Derived Microbiological and Immune Signatures: Applications in Adaptive Risk Assessment of Infectious Disease During Spaceflight
Infectious diseases represent an urgent risk for spaceflight with consequences ranging from loss in crew performance to crew incapacitation or loss of life should an outbreak occur. The resident environmental microbiome on the International Space Station has been monitored through routine surveillance over almost twenty years, beginning with culture-based microbial detection which has advanced to molecular methods in recent years. This has created a wealth of data that we have begun mining to define the microbial ecology of the ISS. Summarized here is our analysis of data from the historical microbial population defined by culture-based monitoring from the past two decades, organized by their likelihood to cause disease into clinical categories. As expected, many residents of the normal microflora in environments where people work and live were detected. However, some known pathogens were also detected. As the spaceflight environment can predispose humans to infection, crew health records were used to source additional data for the set to uncover clinical relevance. Data mining was performed on crew health records to capture adverse health events that may be related to infectious disease. Machine learning, specifically Random Forest analysis, was used to analyze the microbial and crew health datasets. The symptom categories were not explained by the ranked bacteria, due to lack of sufficient data for some categories and due to poor ranking of the pathogens for others. Poor ranking of the bacteria could be due to the clinical symptoms being linked to other disease-causing factors, such as allergy or viral infection. These findings suggest a lack of relationship between bacteria detected on surfaces in the ISS and historical health events experienced by astronauts.
Kristyn Hoffman↗
Early detection of disease program: Evaluation of the cellular immune response
The early cellular responses of specific components of the leukocyte and epithelial cell populations to foreign challenges of both an infectious and noninfectious character were evaluated. Procedures for screening potential flight crews were developed, documented, and tested on a control population. Methods for preparing suitable populations of lymphocytes, polymorphonuclear leukocytes, macrophages, and epithelial cells were first established and evaluated. Epithelial cells from viral infected individuals were screened with a number of anti-viral antisera. This procedure showed the earliest indication of disease as well as providing a specific diagnosis to the physicians. Both macrophages and polymorphonuclear leukocytes were studied from normal individuals, smokers, and patients with viral infections. Newer techniques enabling better definition of lymphocyte subpopulations were then developed, namely the E and EAC rosette procedures for recognition of T (thymus-derived) and B (bone-marrow-derived) lymphocyte subpopulations. Lymphocyte and lymphocyte subpopulation response to multiple mitogens have been evaluated.
Criswell, B. S.↗
Emerging and Reemeriging Human Bunyavirus Infections and Climate Change
The Bunyaviridae family includes a growing number of viruses that have contributed to the burden of emerging and reemerging infectious diseases around the globe. Many of these viruses cause severe clinical outcomes in human and animal populations, the results of which can be detrimental to public health and the economies of affected communities. The threat to endemic and non-native regions is particularly high, and national and international public health agencies are often on alert. Many of the bunyaviruses cause severe clinical disease including hemorrhage, organ failure, and death leading to their high-risk classification. Hantaviruses and Rift Valley fever virus (RVFV) (genus Phlebovirus) are National Institute of Allergy and Infectious Diseases Category A priority pathogens in the United States. Viral hemorrhagic fevers, a classification that includes many bunyaviruses, are immediately notifiable in the European Union. The emergence of new and reemerging bunyaviruses has resulted in numerous human and animal fatalities. Outbreaks of Rift Valley fever (RVF) in East Africa (1997/1998, 2006/2007), Sudan (2007), Southern Africa (2008-2010), Kenya (1997/1998, 2006/2007) (Anyamba et al., 2009, 2010; Breiman et al., 2010; Grobbelaar et al., 2011; Woods et al., 2002) and Saudi Arabia & Yemen (2000, 2010) (Food and Agriculture Organization, 2000; Hjelle and Glass, 2000; Madani et al., 2003) and the emergence of Sin Nombre virus (1993) (Hjelle and Glass, 2000) and most recently Schmallenberg virus (2011) (DEFRA, 2012) are prime examples of the devastating and worldwide toll bunyaviruses have on health and economies. Climate variability (precipitation and temperature in particular) greatly influence the ecological conditions that drive arboviral disease outbreaks across the globe. Several human and animal disease outbreaks have been influenced by changes in climate associated with the El Niño Southern Oscillation (ENSO) phenomenon including the bunyaviruses RVFV and Sin Nombre (an etiologic agent of hantavirus pulmonary syndrome (HPS)), as well as Murray Valley encephalitis, chikungunya, and malaria to name but a few (Anyamba et al., 2009; Bouma and Dye, 1997; Chretien et al., 2007; Engelthaler et al., 1999; Kovats et al., 2003; Linthicum et al., 1999; Nicholls, 1986). Most bunyaviruses exhibit episodic outbreak patterns with seasonal or annual trends dependent upon climate conditions, vector abundance, and the proximity of a susceptible population. The implications for continued climate change are dire, especially with regard to vector-borne diseases, many of which can cause severe morbidity, sequelae, and death. Increased rainfall and widening endemicity as a result of climate change, compounded by the emergence of new viruses, poses a serious threat to a greater geographic range beyond the regions of endemicity.
Bunyavirus↗