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All sources NASA NTRS DOE OSTI

DOE OSTI2020

Sneezing and asymptomatic virus transmission

The novel coronavirus disease (COVID-19) spread pattern continues to show that geographical barriers alone cannot contain a virus. Asymptomatic carriers play a critical role in the nature of this virus quickly escalating into a global pandemic. Asymptomatic carriers may transmit the virus unintentionally through sporadic sneezing. A novel Computational Fluid Dynamics (CFD) approach has been proposed with a realistic modeling of a human sneeze achieved by the combination of state-of-the-art experimental and numerical methods. This modeling approach may be suitable for future engineering analyses aimed at reshaping public spaces and common areas, with the main objective to accurately predict the spread of aerosol and droplets that may contain pathogens. This study shows that the biomechanics of a human sneeze, including complex muscle contractions and relaxations, can be accurately modeled by the angular head motion and the dynamic pressure response during sneezing. These have been considered as the human factors and were implemented in the CFD simulation by imposing a momentum source term to the coupled Eulerian–Lagrangian momentum equations. The momentum source was modeled by the measured dynamic pressure response in conjunction with the angular head motion. This approach eliminated the need to create an ad hoc set of inlet boundary conditions. With this proposed technique, it is easier to add multiple fixed and/or moving sources of sneezes in complex computational domains. Additionally, extensive sensitivity analyses based on different environmental conditions were performed, and their impact was described in terms of potential virus spread.

42 ENGINEERING↗

DOE OSTI2021

Methane-derived carbon flows into host–virus networks at different trophic levels in soil

Significance The impact of soil viruses on prokaryotic hosts and their functional processes is largely unknown. While metagenomic sequencing of soil microbial communities enables identification of linkages between viruses and hosts, this does not necessarily identify contemporary interactions. To enable a detailed analysis of active virus–host interactions between individual populations, we focused on the critical biogeochemical process of methane (CH 4 ) oxidation and followed the transfer of carbon from hosts to their associated viruses in situ. Analysis of 13 C-enriched metagenomic DNA demonstrated that CH 4 -derived carbon is transferred into viral biomass via both primary and secondary utilizers of CH 4 and suggests viral predation is an important mechanism for releasing CH 4 -derived organic carbon into the soil matrix.

Lee, Sungeun↗

DOE OSTI2020

Inducible epithelial resistance against acute Sendai virus infection prevents chronic asthma‐like lung disease in mice

Background and Purpose Respiratory viral infections play central roles in the initiation, exacerbation and progression of asthma in humans. An acute paramyxoviral infection in mice can cause a chronic lung disease that resembles human asthma. We sought to determine whether reduction of Sendai virus lung burden in mice by stimulating innate immunity with aerosolized Toll‐like receptor (TLR) agonists could attenuate the severity of chronic asthma‐like lung disease. Experimental Approach Mice were treated by aerosol with 1‐μM oligodeoxynucleotide (ODN) M362, an agonist of the TLR9 homodimer, and 4‐μM Pam2CSK4 (Pam2), an agonist of the TLR2/6 heterodimer, within a few days before or after Sendai virus challenge. Key Results Treatment with ODN/Pam2 caused ~75% reduction in lung Sendai virus burden 5 days after challenge. The reduction in acute lung virus burden was associated with marked reductions 49 days after viral challenge in eosinophilic and lymphocytic lung inflammation, airway mucous metaplasia, lumenal mucus occlusion and hyperresponsiveness to methacholine. Mechanistically, ODN/Pam2 treatment attenuated the chronic asthma phenotype by suppressing IL‐33 production by type 2 pneumocytes, both by reducing the severity of acute infection and by down‐regulating Type 2 (allergic) inflammation. Conclusion and Implications These data suggest that treatment of susceptible human hosts with aerosolized ODN and Pam2 at the time of a respiratory viral infection might attenuate the severity of the acute infection and reduce initiation, exacerbation and progression of asthma.

Goldblatt, David L.↗

DOE OSTI2023

Single-dose mucosal replicon-particle vaccine protects against lethal Nipah virus infection up to 3 days after vaccination

Nipah virus (NiV) causes a highly lethal disease in humans who present with acute respiratory or neurological signs. No vaccines against NiV have been approved to date. Here, we report on the clinical impact of a novel NiV-derived nonspreading replicon particle lacking the fusion (F) protein gene (NiVΔF) as a vaccine in three small animal models of disease. A broad antibody response was detected that included immunoglobulin G (IgG) and IgA subtypes with demonstrable Fc-mediated effector function targeting multiple viral antigens. Single-dose intranasal vaccination up to 3 days before challenge prevented clinical signs and reduced virus levels in hamsters and immunocompromised mice; decreases were seen in tissues and mucosal secretions, critically decreasing potential for virus transmission. This virus replicon particle system provides a vital tool to the field and demonstrates utility as a highly efficacious and safe vaccine candidate that can be administered parenterally or mucosally to protect against lethal Nipah disease.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2020

Estimating the Timing of Early Simian-Human Immunodeficiency Virus Infections: a Comparison between Poisson Fitter and BEAST

Many HIV prevention strategies are currently under consideration where it is highly informative to know the study participants’ times of infection. These can be estimated using viral sequence data sampled early in infection. However, there are several scenarios that, if not addressed, can skew timing estimates. These include multiple transmitted/founder (TF) viruses, APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like)-mediated mutational enrichment, and recombination. Here, we suggest a pipeline to identify these problems and resolve the biases that they introduce. We then compare two modeling strategies to obtain timing estimates from sequence data. The first, Poisson Fitter (PF), is based on a Poisson model of random accumulation of mutations relative to the TF virus (or viruses) that established the infection. The second uses a coalescence-based phylogenetic strategy as implemented in BEAST. The comparison is based on timing predictions using plasma viral RNA (cDNA) sequence data from 28 simian-human immunodeficiency virus (SHIV)-infected animals for which the exact day of infection is known. In this particular setting, based on nucleotide sequences from samples obtained in early infection, the Poisson method yielded more accurate, more precise, and unbiased estimates for the time of infection than did the explored implementations of BEAST. The inference of the time of infection is a critical parameter in testing the efficacy of clinical interventions in protecting against HIV-1 infection. For example, in clinical trials evaluating the efficacy of passively delivered antibodies (Abs) for preventing infections, accurate time of infection data are essential for discerning levels of the Abs required to confer protection, given the natural Ab decay rate in the human body. In such trials, genetic sequences from early in the infection are regularly sampled from study participants, generally prior to immune selection, when the viral population is still expanding and genetic diversity is low. In this particular setting of early viral growth, the Poisson method is superior to the alternative approach based on coalescent methods. This approach can also be applied in human vaccine trials, where accurate estimates of infection times help ascertain if vaccine-elicited immune protection wanes over time.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2024

Data for Rapid and Efficient in planta Genome Editing in Sorghum Using Foxtail Mosaic Virus-mediated sgRNA Delivery

The requirement of in vitro tissue culture for the delivery of gene editing reagents limits the application of gene editing to commercially relevant varieties of many crop species. To overcome this bottleneck, plant RNA viruses have been deployed as versatile tools for in planta delivery of recombinant RNA. Viral delivery of single-guide RNAs (sgRNAs) to transgenic plants that stably express CRISPR-associated (Cas) endonuclease has been successfully used for targeted mutagenesis in several dicotyledonous and few monocotyledonous plants. Progress with this approach in monocotyledonous plants is limited so far by the availability of effective viral vectors. We engineered a set of foxtail mosaic virus (FoMV) and barley stripe mosaic virus (BSMV) vectors to deliver the fluorescent protein AmCyan to track viral infection and movement in Sorghum bicolor . We further used these viruses to deliver and express sgRNAs to Cas9 and Green Fluorescent Protein (GFP) expressing transgenic sorghum lines, targeting Phytoene desaturase (PDS), Magnesium-chelatase subunit I (MgCh), 4-hydroxy-3-methylbut-2-enyl diphosphate reductase, orthologs of maize Lemon white1 (Lw1) or GFP. The recombinant BSMV did neither infect sorghum nor deliver or express AmCyan and sgRNAs. In contrast, the recombinant FoMV systemically spread throughout sorghum plants and induced somatic mutations with frequencies reaching up to 60%. This mutagenesis led to visible phenotypic changes, demonstrating the potential of FoMV for in planta gene editing and functional genomics studies in sorghum.

Feedstock Production↗

DOE OSTI2022

Lactiplantibacillus plantarum 0111 Protects Against Influenza Virus by Modulating Intestinal Microbial-Mediated Immune Responses

There are some limitations of traditional influenza vaccines concerning novel mutant strains. Therefore, it is particularly important to develop preventive means for antigen-unrelated types of influenza viruses. Recent studies have shown that probiotics can modulate the immune system and reduce the severity of viral infections. In this study, we investigated the potential of Lactiplantibacillus plantarum 0111 against influenza virus H9N2. Challenge experiments showed that L. plantarum 0111 pretreatments could effectively improve mice’s survival rate and weight loss and reduce the inflammatory cytokines IL-6 and TNF-α in the lungs and bronchoalveolar lavage fluid (BALF) along with the degree of lung and intestinal injury. FMT experiment demonstrates that the protective effect produced by L. plantarum 0111 is associated with gut microorganisms. In addition, 16S high-throughput sequencing of the mouse intestinal microbiota showed that L. plantarum 0111 remodeled the intestinal microbiota after H9N2 infection and maintained the gut microbiota balance. In a mouse model, the oral administration of L. plantarum 0111 increased IFN-β expression in the serum and BALF. At the same time, the transcript levels of IFN-β and related ISGs in the intestine and lungs of mice were also increased. In addition, the activation and polarization of T cells in mesenteric lymph nodes (MLNs) and the spleen were detected by flow cytometry, and the results showed that L. plantarum 0111 modulated cytokines in T cells and increased IgA expression in B cells in the MLNs and spleen. Thus, L. plantarum 0111 may improve gut microbiota-mediated immune responses and thus, resist infection by the influenza virus, and it could be used as an effective preventive measure against the influenza virus.

Xing, Jun-Hong↗

DOE OSTI2022

A Novel and Secure Pseudovirus Reporter System Based Assay for Neutralizing and Enhancing Antibody Assay Against Marburg Virus

Marburg virus (MARV) is one of the principal members of the filovirus family, which can cause fatal hemorrhagic fever in humans. There are currently no prophylactic and therapeutic drugs on the market, and the high pathogenicity and infectivity of MARV make its research highly dependent on biosafety level 4 conditions, severely hindering the development of vaccines and therapies. Therefore, the development of medicines, such as MARV serological diagnosis, vaccines, and therapeutic antibody drugs, urgently needs a safe, convenient, and biosafety level 2 detection method to measure the neutralizing activity of MARV antibodies. To this end, we report a neutralization assay relying on a Rabies virus (RABV) reverse genetic operating system. We constructed infectious clones carrying the eGFP reporter gene and the full length of the original unmodified MARV GP gene. Based on the critical parameters of phylogenetic analysis, recombinant viruses targeting representative strains in the two major MARV lineages were successfully rescued. These pseudoviruses are safe in mice, and their inability to infect cells after being neutralized by antibodies can be visualized under a fluorescence microscope. We tested the system using the neutralizing antibody MR191. MR191 can significantly block the infection of BSR cells with pseudovirus. We compared it with the traditional lentivirus-type pseudovirus system to verify the system’s credibility and obtained the same results as reported in the literature. In general, we have established a safe and visualized method for evaluating the neutralizing activity of MARV antibodies. Compared with traditional methods, it has the advantages of convenient operation, short cycle, and low cost. It is a candidate method that can replace actual viruses for a neutralization assay.

Bi, Jinhao↗

DOE OSTI2024

Recombinant Vaccine Strain ASFV-G-Δ9GL/ΔUK Produced in the IPKM Cell Line Is Genetically Stable and Efficacious in Inducing Protection in Pigs Challenged with the Virulent African Swine Fever Virus Field Isolate Georgia 2010

We have previously reported that the recombinant African Swine Fever (ASF) vaccine candidate ASFV-G-Δ9GL/ΔUK efficiently induces protection in domestic pigs challenged with the virulent strain Georgia 2010 (ASFV-G). As reported, ASFV-G-Δ9GL/ΔUK induces protection, while intramuscularly (IM), administered at doses of 10 4 HAD 50 or higher, prevents ASF clinical disease in animals infected with the homologous ASFV g strain. Like other recombinant vaccine candidates obtained from ASFV field isolates, ASFV-G-Δ9GL/ΔUK stocks need to be produced in primary cultures of swine macrophages, which constitutes an important limitation in the production of large virus stocks at the industrial level. Here, we describe the development of ASFV-G-Δ9GL/ΔUK stocks using IPKM (Immortalized Porcine Kidney Macrophage) cells, which are derived from swine macrophages. We show that ten successive passages of ASFV-G-Δ9GL/ΔUK in IPKM cells induced small changes in the virus genome. The produced virus, ASFV-G-Δ9GL/ΔUKp10, presented a similar level of replication in swine macrophages cultures to that of the original ASFV-G-Δ9GL/ΔUK (ASFV-G-Δ9GL/ΔUKp0). The protective efficacy of ASFV-G-Δ9GL/ΔUKp10 was evaluated in pigs that were IM-inoculated with either 10 4 or 10 6 HAD 50 of ASFV-G-Δ9GL/ΔUKp10. While animals inoculated with 10 4 HAD 50 present a partial protection against the experimental infection with the virulent parental virus ASFV-G, those inoculated with 10 6 HAD 50 were completely protected. Therefore, as was just recently reported for another ASF vaccine candidate, ASFV-G-ΔI177L, IPKM cells are an effective alternative to produce stocks for vaccine strains which only grow in swine macrophages.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2021

Protection against Different Genotypes of Newcastle Disease Viruses (NDV) Afforded by an Adenovirus-Vectored Fusion Protein and Live NDV Vaccines in Chickens

The efficacy of an adenovirus-vectored Newcastle disease virus (NDV) vaccine expressing the fusion (F) NDV protein (adeno-F) was evaluated against challenges with virulent heterologous and homologous NDV strains to the F protein. In a preliminary study, two different doses (low and high) of adeno-F were tested against a virulent NDV strain containing the homologous NDV F protein, CA02. In a second study, at three weeks post-vaccination, the efficacy of the high dose of adeno-F was compared to a live attenuated NDV vaccine strain (LaSota) against three antigenically distinct virulent NDV challenge strains, one homologous (CA02) and two heterologous (TZ12, EG14) to F in the vectored vaccine. In both experiments, clinical signs, mortality, virus shedding, and humoral response were evaluated. In the first experiment, the survival rates from birds vaccinated with adeno-F at a high and low dose were 100% and 25%, respectively. In the second experiment, birds vaccinated with the high dose of adeno-F had a survival rate of 80%, 75%, and 65% after challenge with the CA02, TZ12, and EG14 viruses, respectively. All of the LaSota-vaccinated birds survived post-challenge no matter the NDV challenge strain. High antibody titers were detected after vaccination with LaSota by HI and ELISA tests. The majority of adeno-F-vaccinated birds had detectable antibodies using the ELISA test, but not using the HI test, before the challenge. The data show that both the similarity of the F protein of the adeno-F vaccine to the challenge virus and the adeno-F vaccination dose affect the efficacy of an adenovirus-vectored NDV vaccine against a virulent NDV challenge.

Ferreira, Helena L. (ORCID:0000000232613712)↗

NASA NTRS1999

Latent Viruses: A Space Travel Hazard??

A major issue associated with long-duration space flight is the possibility of infectious disease causing an unacceptable medical risk to crew members. Our proposal is designed to gain information that addresses several issues outlined in the Immunology/Infectious disease critical path. The major hypothesis addressed is that space flight causes alterations in the immune system that may allow latent viruses which are endogenous in the human population to reactivate and shed to higher levels than normal which can affect the health of crew members during a long term space-flight mission. We will initially focus our studies on the human herpesviruses and human polyomaviruses which are important pathogens known to establish latent infections in the human population. Both primary infection and reactivation from latent infection with this group of viruses can cause a variety of illnesses that result in morbidity and occasionally mortality of infected individuals. Effective vaccines exist for only one of the eight known human herpesviruses and the vaccine itself can still reactivate from latent infection. Available antivirals are of limited use and are effective against only a few of the human herpesviruses. Although most individuals display little if any clinical consequences from latent infection, events which alter immune function such as immunosuppressive therapy following solid organ transplantation are known to increase the risk of developing complications as a result of latent virus reactivation. This proposal will measure both the frequency and magnitude of viral shedding and genome loads in the blood from humans participating in activities that serve as ground based models of space flight conditions. Our initial goal is to develop sensitive quantitative competitive PCR- based assays (QC-PCR) to detect the herpesvirus Epstein-Barr virus (EBV), and the polyomaviruses SV40, BKV, and JCV. Using these assays we will establish baseline patterns of viral genome load in the blood and viral shedding from normal volunteers in a longitudinal study over I year in length. As a comparison, we will measure patterns of viral genome loads and shedding from individuals who are severely immunosuppressed, in whom herpesvirus reactivation or primary infection with a herpesvirus is known to cause complications. In addition, we will proceed to testing ground based analogs in collaboration with Dr. Duane Pierson (Lyndon B. Johnson Space Center). This will include measuring samples obtained from individuals living and working in the extreme environment of Antarctica. We expect to detect viral shedding or reactivation from most of the test groups, although the magnitude of shedding or reactivation cannot be predicted. The data accumulated from studies in this proposal should allow us to evaluate whether events that simulate certain aspects of space flight reactivate viral infections severe enough in nature that they may compromise the success of long-term space flight missions. These studies will also provide a foundation to monitor viral reactivation and shedding from crew members participating in actual space flight missions. We will present data showing the establishment of our QC-PCR assay for detection of EBV.

Ling, P. D.↗

NASA NTRS2001

Routine detection of Epstein-Barr virus specific T-cells in the peripheral blood by flow cytometry

The ability to detect cytomegalovirus-specific T-cells (CD4(+)) in the peripheral blood by flow cytometry has been recently described by Picker et al. In this method, cells are incubated with viral antigen and responding (cytokine producing) T-cells are then identified by flow cytometry. To date, this technique has not been reliably used to detect Epstein-Barr virus (EBV)-specific T-cells primarily due to the superantigen/mitogenic properties of the virus which non-specifically activate T-cells. By modifying culture conditions under which the antigens are presented, we have overcome this limitation and developed an assay to detect and quantitate EBV-specific T-cells. The detection of cytokine producing T-cells by flow cytometry requires an extremely strong signal (such as culture in the presence of PMA and ionomycin). Our data indicate that in modified culture conditions (early removal of viral antigen) the non-specific activation of T-cells by EBV is reduced, but antigen presentation will continue uninhibited. Using this method, EBV-specific T-cells may be legitimately detected using flow cytometry. No reduction in the numbers of antigen-specific T-cells was observed by the early removal of target antigen when verified using cytomegalovirus antigen (a virus with no non-specific T-cell activation properties). In EBV-seropositive individuals, the phenotype of the EBV-specific cytokine producing T-cells was evaluated using four-color flow cytometry and found to be CD45(+), CD3(+), CD4(+), CD45RA(-), CD69(+), CD25(-). This phenotype indicates the stimulation of circulating previously unactivated memory T-cells. No cytokine production was observed in CD4(+) T-cells from EBV-seronegative individuals, confirming the specificity of this assay. In addition, the use of four color cytometry (CD45, CD3, CD69, IFNgamma/IL-2) allows the total quantitative assessment of EBV-specific T-cells while monitoring the interference of EBV non-specific mitogenic activity. This method may have significant utility for the monitoring of the immune response to latent virus infection/reactivation.

Non-NASA Center↗

NASA NTRS1993

Phosphate cycling on the basic protein of Plodia interpunctella granulosis virus

The presence of infected cell-specific phosphoproteins was investigated in Plodia interpunctella granulosis virus (PiGV)-infected fat body using [32P]orthophosphoric acid labeling. One infected cell-specific phosphoprotein had a mobility similar to that of the basic protein (VP12) of PiGV. Further analysis, using immunoblotting and acid-urea gel analysis of infected fat body, confirmed that this phosphoprotein was VP12. However we did not detect phosphorylated VP12 in 32P-labeled nucleocapsids. Phosphoamino acid analysis of 32P-labeled VP12 revealed that phosphoserine was present in the basic protein. Since VP12 is phosphorylated in the infected cell, but not in the nucleocapsid, it appears that dephosphorylation of VP12 is a critical event in the life cycle of the virus. We therefore assayed virus nucleocapsids and infected fat body for the presence of phosphatase activity. Phosphatase activity was not detected in the virus, but the infected fat body had more activity than uninfected fat body. A model for nucleocapsid assembly and uncoating is presented which takes into account the phosphorylation state of VP12, the role of Zn2+ in the nucleocapsid, and the role of the capsid-associated kinase.

NASA Discipline Cell Biology↗

NASA NTRS1992

Production and characterization of monoclonal antibodies to budgerigar fledgling disease virus major capsid protein VP

Eleven hybridoma cell lines producing monoclonal antibodies (MAbs) against intact budgerigar fledgling disease (BFD) virions were produced and characterized. These antibodies were selected for their ability to react with BFD virions in an enzyme-linked immunosorbent assay. Each of these antibodies was reactive in the immunofluorescent detection of BFD virus-infected cells. These antibodies immunoprecipitated intact virions and specifically recognized the major capsid protein, VP1, of the dissociated virion. The MAbs were found to preferentially recognize native BFD virus capsid protein when compared with denatured virus protein. These MAbs were capable of detecting BFD virus protein in chicken embryonated cell-culture lysates by dot-blot analysis.

Non-NASA Center↗

NASA NTRS1992

Phosphorylation of the budgerigar fledgling disease virus major capsid protein VP1

The structural proteins of the budgerigar fledgling disease virus, the first known nonmammalian polyomavirus, were analyzed by isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The major capsid protein VP1 was found to be composed of at least five distinct species having isoelectric points ranging from pH 6.45 to 5.85. By analogy with the murine polyomavirus, these species apparently result from different modifications of an initial translation product. Primary chicken embryo cells were infected in the presence of 32Pi to determine whether the virus structural proteins were modified by phosphorylation. SDS-PAGE of the purified virus structural proteins demonstrated that VP1 (along with both minor capsid proteins) was phosphorylated. Two-dimensional analysis of the radiolabeled virus showed phosphorylation of only the two most acidic isoelectric species of VP1, indicating that this posttranslational modification contributes to VP1 species heterogeneity. Phosphoamino acid analysis of 32P-labeled VP1 revealed that phosphoserine is the only phosphoamino acid present in the VP1 protein.

Non-NASA Center↗

NASA NTRS2004

Freeing Water from Viruses and Bacteria

Four years ago, Argonide Corporation, a company focused on the research, production, and marketing of specialty nano materials, was seeking to develop applications for its NanoCeram[R] fibers. Only 2 nanometers in diameter, these nano aluminum oxide fibers possessed unusual bio-adhesive properties. When formulated into a filter material, the electropositive fibers attracted and retained electro-negative particles such as bacteria and viruses in water-based solutions. This technology caught the interest of NASA as a possible solution for improved water filtration in space cabins. NASA's Johnson Space Center awarded Sanford, Florida-based Argonide a Phase I Small Business Innovation Research (SBIR) contract to determine the feasibility of using the company's filter for purifying recycled space cabin water. Since viruses and bacteria can be carried aboard space cabins by space crews, the ability to detect and remove these harmful substances is a concern for NASA. The Space Agency also desired an improved filter to polish the effluent from condensed and waste water, producing potable drinking water. During its Phase I partnership with NASA, Argonide developed a laboratory-size filter capable of removing greater than 99.9999 percent of bacteria and viruses from water at flow rates more than 200 times faster than virus-rated membranes that remove particles by sieving. Since the new filter s pore size is rather large compared to other membranes, it is also less susceptible to clogging by small particles. In September 2002, Argonide began a Phase II SBIR project with Johnson to develop a full-size cartridge capable of serving a full space crew. This effort, which is still ongoing, enabled the company to demonstrate that its filter media is an efficient absorbent for DNA and RNA.

Source record↗

NASA NTRS2007

Monitoring Immune System Function and Reactivation of Latent Viruses in the Artificial Gravity Pilot Study

Numerous studies have indicated that dysregulation of the immune system occurs during or after spaceflight. Using 21 day -6 degrees head-down tilt bed rest as a spaceflight analog, this study describes the effects of artificial gravity (AG) as a daily countermeasure on immunity, stress and reactivation of clinically important latent herpes viruses. The specific aims were to evaluate psychological and physiological stress, to determine the status of the immune system, and to quantify reactivation of latent herpes viruses. Blood, saliva, and urine samples were collected from each participating subject at different times throughout the study. An immune assessment was performed on all treatment and control subjects that consisted of a comprehensive peripheral immunophenotype analysis, intracellular cytokine profiles and a measurement of T cell function. The treatment group displayed no differences throughout the course of the study with regards to peripheral leukocyte distribution, cytokine production or T cell function. Shedding of Epstein barr virus (EBV), Cytomegalovirus (CMV), and Varicella zoster virus (VZV) was quantified by real time PCR in saliva and urine samples, respectively. There was no significant difference in CMV DNA in the treatment group as compared to the control group. EBV and VZV on the other hand showed a mild reactivation during the study. There were no significant differences in cortisol between the control and treatment groups. In addition, no significant differences between antiviral antibody titers (EBV-VCA, -EA, -EBNA, CMV) or tetramer-positive (EBV, CMV) were found between the two groups. EBV DNA copies in blood were typically undetectable but never exceeded 1,500 copies per 106 PBMCs. Overall, these data indicate that the artificial gravity countermeasure and the 21 day head-down tilt bed rest regimen had no observable adverse effect on immune function.

Mehta, Satish K.↗

NASA NTRS2011

Rapid Detection of the Varicella Zoster Virus

1.Technology Description-Researchers discovered that when the Varicella Zoster Virus (VZV) reactivates from latency in the body, the virus is consistently present in saliva before the appearance of skin lesions. A small saliva sample is mixed with a specialized reagent in a test kit. If the virus is present in the saliva sample, the mixture turns a red color. The sensitivity and specificity emanates from an antibody-antigen reaction. This technology is a rapid, non-invasive, point of-of-care testing kit for detecting the virus from a saliva sample. The device is easy to use and can be used in clinics and in remote locations to quickly detect VZV and begin treatment with antiviral drugs. 2.Market Opportunity- RST Bioscience will be the first and only company to market a rapid, same day test kit for the detection of VZV in saliva. The RST detection test kit will have several advantages over existing, competitive technology. The test kit is self contained and laboratory equipment is not required for analysis of the sample. Only a single saliva sample is required to be taken instead of blood or cerebral spinal fluid. The test kit is portable, sterile and disposable after use. RST detection test kits require no electrical power or expensive storage equipment and can be used in remote locations. 3.Market Analysis- According to the CDC, it is estimated that 1 million cases of shingles occur each year in the U.S. with more than half over the age of sixty. There is a high demand for rapid diagnostics by the public. The point-of-care testing (POCT) market is growing faster than other segments of in vitro diagnostics. According to a July 2007 InteLab Corporation industry report the overall market for POCT was forecast to increase from $10.3 billion in 2005 to $18.7 billion by 2011. The market value of this test kit has not been determined. 4.Competition- The VZV vaccine prevents 50% of cases and reduces neuralgia by 66%. The most popular test detects VZV-specific IgM antibody in blood. Other tests include running a sample in a polymerase chain reaction analyzer, enzyme immunoassay, latex agglutination, indirect fluorescent antibody and fluorescent antibody to membrane antigen assay. These existing tests require laboratory analysis by trained personnel, expensive equipment, invasive procedures and a longer period of time to obtain test results.

Lewis, Michelle P.↗