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At least 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
NASA NTRS2003

Resistance of virus to extinction on bottleneck passages: study of a decaying and fluctuating pattern of fitness loss

RNA viruses display high mutation rates and their populations replicate as dynamic and complex mutant distributions, termed viral quasispecies. Repeated genetic bottlenecks, which experimentally are carried out through serial plaque-to-plaque transfers of the virus, lead to fitness decrease (measured here as diminished capacity to produce infectious progeny). Here we report an analysis of fitness evolution of several low fitness foot-and-mouth disease virus clones subjected to 50 plaque-to-plaque transfers. Unexpectedly, fitness decrease, rather than being continuous and monotonic, displayed a fluctuating pattern, which was influenced by both the virus and the state of the host cell as shown by effects of recent cell passage history. The amplitude of the fluctuations increased as fitness decreased, resulting in a remarkable resistance of virus to extinction. Whereas the frequency distribution of fitness in control (independent) experiments follows a log-normal distribution, the probability of fitness values in the evolving bottlenecked populations fitted a Weibull distribution. We suggest that multiple functions of viral genomic RNA and its encoded proteins, subjected to high mutational pressure, interact with cellular components to produce this nontrivial, fluctuating pattern.

Serial Passage↗
NASA NTRS2010

Latent Virus Reactivation in Astronauts and Shingles Patients

Spaceflight is a uniquely stressful environment with astronauts experiencing a variety of stressors including: isolation and confinement, psychosocial, noise, sleep deprivation, anxiety, variable gravitational forces, and increased radiation. These stressors are manifested through the HPA and SAM axes resulting in increased stress hormones. Diminished T-lymphocyte functions lead to reactivation of latent herpesviruses in astronauts during spaceflight. Herpes simplex virus reactivated with symptoms during spaceflight whereas Epstein-Barr virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV) reactivate and are shed without symptoms. EBV and VZV are shed in saliva and CMV in the urine. The levels of EBV shed in astronauts increased 10-fold during the flight; CMV and VZV are not typically shed in low stressed individuals, but both were shed in astronauts during spaceflight. All herpes viruses were detected by polymerase chain reaction (PCR) assay. Culturing revealed that VZV shed in saliva was infectious virus. The PCR technology was extended to test saliva of 54 shingles patients. All shingles patients shed VZV in their saliva, and the levels followed the course of the disease. Viremia was also found to be common during shingles. The technology may be used before zoster lesions appear allowing for prevention of disease. The technology may be used for rapid detection of VZV in doctors offices. These studies demonstrated the value of applying technologies designed for astronauts to people on Earth.

Mehta, Satish K.↗
NASA NTRS2010

Salivary Varicella Zoster Virus in Astronauts and in Patients of Herpes Zoster

Spaceflight is a uniquely stressful environment with astronauts experiencing a variety of stressors including: isolation and confinement, psychosocial, noise, sleep deprivation, anxiety, variable gravitational forces, and increased radiation. These stressors are manifested through the HPA and SAM axes resulting in increased stress hormones. Diminished T-lymphocyte functions lead to reactivation of latent herpes viruses in astronauts during spaceflight. Herpes simplex virus reactivated with symptoms during spaceflight whereas Epstein-Barr virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV) reactivate and are shed without symptoms. EBV and VZV are shed in saliva and CMV in the urine. The levels of EBV shed in astronauts increased 10-fold during the flight; CMV and VZV are not typically shed in low stressed individuals, but both were shed in astronauts during spaceflight. All herpesviruses were detected by polymerase chain reaction (PCR) assay. Culturing revealed that VZV shed in saliva was infectious virus. The PCR technology was extended to test saliva of 54 shingles patients. All shingles patients shed VZV in their saliva, and the levels followed the course of the disease. Viremia was also found to be common during shingles. The technology may be used before zoster lesions appear allowing for prevention of disease. The technology may be used for rapid detection of VZV in doctors? offices. These studies demonstrated the value of applying technologies designed for astronauts to people on Earth.

Mehta, Satish↗
NASA NTRS2011

Latent Virus Reactivation in Space Shuttle Astronauts

Latent virus reactivation was measured in 17 astronauts (16 male and 1 female) before, during, and after short-duration Space Shuttle missions. Blood, urine, and saliva samples were collected 2-4 months before launch, 10 days before launch (L-10), 2-3 hours after landing (R+0), 3 days after landing (R+14), and 120 days after landing (R+120). Epstein-Barr virus (EBV) DNA was measured in these samples by quantitative polymerase chain reaction. Varicella-zoster virus (VZV) DNA was measured in the 381 saliva samples and cytomegalovirus (CMV) DNA in the 66 urine samples collected from these subjects. Fourteen astronauts shed EBV DNA in 21% of their saliva samples before, during, and after flight, and 7 astronauts shed VZV in 7.4% of their samples during and after flight. It was interesting that shedding of both EBV and VZV increased during the flight phase relative to before or after flight. In the case of CMV, 32% of urine samples from 8 subjects contained DNA of this virus. In normal healthy control subjects, EBV shedding was found in 3% and VZV and CMV were found in less than 1% of the samples. The circadian rhythm of salivary cortisol measured before, during, and after space flight did not show any significant difference between flight phases. These data show that increased reactivation of latent herpes viruses may be associated with decreased immune system function, which has been reported in earlier studies as well as in these same subjects (data not reported here).

Mehta, S. K.↗
NASA NTRS2015

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↗
DOE OSTI2025

DNA viruses from different stages of a wastewater treatment plant in southwest Ohio

Wastewater treatment plants (WWTPs) house diverse populations of microbial communities that are dynamic across treatment stages. Although viruses, especially non-pathogenic ones are relatively less studied compared to their bacterial counterparts, they are equally important players in WWTP microbiomes. In this study, we sampled influent, activated sludge, and effluent stages of a WWTP in southwest Ohio to sequence their viral population using multiple displacement amplification (MDA) and metagenomic approaches. We recovered 1003 viral genomes, the majority of which were ssDNA (single-stranded DNA) viruses that formed distinct clusters representing novel species and phylogenetic groups not closely related to known human gut or terrestrial viruses. Additionally, tracking viruses across treatment stages showed several persisted across multiple treatment stages. These results suggest that further studies are needed to understand the persistence of viral populations, particularly non-pathogenic ones, across different stages of WWTPs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Rapid and efficient in planta genome editing in sorghum using foxtail mosaic virus‐mediated sgRNA delivery

SUMMARY 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.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2026

Cryo-EM visualization of viruses from partially irrigated soils

Viruses are numerically the most abundant forms on Earth, and most are present in soil. Even though viruses are highly abundant in soil and critical to rhizosphere function, visualizing the diverse morphotypes within soil has been challenging. The difficulty is primarily due to the heterogenous nature of isolated suspensions that typically contain nanometer to micron scale debris which renders protein crystallography for structural studies unfeasible and hinders cryo-electron microscopy due to ice thickness and contrast issues. Here we employed and compared a simple spin filtration method to cleanup solutions of extracted viruses for direct observation with cryo-electron microscopy. The method employs common physical biochemical separation steps to remove large and small debris which dramatically improves image quality and preservation of structural features to permit visualizing morphotypes not typically seen with conventional negative stain approaches. In addition to tailed and non-tailed polyhedral phages, several under reported or novel morphotypes of soil viruses are directly visualized as a particle library with both 2D and 3D information.

cryo-EM↗
NASA NTRS2001

Elevated stress hormone levels relate to Epstein-Barr virus reactivation in astronauts

OBJECTIVE: The objective of this study was to determine the effects of stress and spaceflight on levels of neuroendocrine hormones and Epstein-Barr virus (EBV)-specific antibodies in astronauts. METHODS: Antiviral antibody titers and stress hormones were measured in plasma samples collected from 28 astronauts at their annual medical exam (baseline), 10 days before launch (L-10), landing day (R+0), and 3 days after landing (R+3). Urinary stress hormones were also measured at L-10 and R+0. RESULTS: Significant increases (p <.01) in EBV virus capsid antigen antibodies were found at all three time points (L-10, R+0, and R+3) as compared with baseline samples. Anti-EBV nuclear antigen antibodies were significantly decreased at L-10 (p <.05) and continued to decrease after spaceflight (R+0 and R+3, p <.01). No changes were found in antibodies to the nonlatent measles virus. The 11 astronauts who showed evidence of EBV reactivation had significant increases in urinary epinephrine and norepinephrine as compared with astronauts without EBV reactivation. CONCLUSION: These findings indicate that physical and psychological stresses associated with spaceflight resulted in decreased virus-specific T-cell immunity and reactivation of EBV.

NASA Center JSC↗
NASA NTRS2000

Simian virus 40, poliovirus vaccines, and human cancer: research progress versus media and public interests

From 1955 through early 1963, millions of people were inadvertently exposed to simian virus 40 (SV40) as a contaminant of poliovirus vaccines; the virus had been present in the monkey kidney cultures used to prepare the vaccines and had escaped detection. SV40 was discovered in 1960 and subsequently eliminated from poliovirus vaccines. This article reviews current knowledge about SV40 and considers public responses to reports in the media. SV40 is a potent tumour virus with broad tissue tropism that induces tumours in rodents and transforms cultured cells from many species. It is also an important laboratory model for basic studies of molecular processes in eukaryotic cells and mechanisms of neoplastic transformation. SV40 neutralizing antibodies have been detected in individuals not exposed to contaminated poliovirus vaccines. There have been many reports of detection of SV40 DNA in human tumours, especially mesotheliomas, brain tumours and osteosarcomas; and DNA sequence analyses have ruled out the possibility that the viral DNA in tumours was due to laboratory contamination or that the virus had been misidentified. However, additional studies are necessary to prove that SV40 is the cause of certain human cancers. A recently published review article evaluated the status of the field and received much media attention. The public response emphasized that there is great interest in the possibility of health risks today from vaccinations received in the past.

Review, Tutorial↗
DOE OSTI2025

Challenges in predicting protein-protein interactions of understudied viruses: Arenavirus-human interactions

Understanding protein-protein interactions (PPIs) between viruses and host organisms is crucial for uncovering infection mechanisms and identifying potential therapeutic targets. The ability to generalize PPI predictive models across understudied viruses presents a significant challenge. In this work, we use arenavirus-human PPIs to illustrate the difficulties associated with model generalization, which are compounded by a lack of both positive and negative data. We employ a Transfer Learning approach to investigate arenavirus-human PPIs by utilizing models trained on better-studied virus-human and human-human PPIs. Additionally, we curate and assess four types of negative sampling datasets to evaluate their impact on model performance. Despite the overall high accuracies (93–99 %) and AUPRC scores (0.8–0.9) appearing promising, further analysis indicates that these performance metrics can be misleading due to data leakage, data bias, and overfitting, especially concerning under-represented viral proteins. We reveal these gaps and assess the impact of data imbalance using standard k-fold cross-validation and Independent Blind Testing with a Balanced Dataset, resulting in a drop in accuracy below 50 %. We propose a viral protein-specific evaluation framework that categorizes viral proteins into majority and minority classes based on their representation in the dataset, enabling comparison of model performance across these groups using balanced accuracies. This framework offers a more robust evaluation of model generalizability, addressing biases inherent in standard evaluation techniques and paving the way for more reliable PPI prediction models for understudied viruses.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

African Swine Fever Virus Protein–Protein Interaction Prediction

The African swine fever virus (ASFV) is an often deadly disease in swine and poses a threat to swine livestock and swine producers. With its complex genome containing more than 150 coding regions, developing effective vaccines for this virus remains a challenge due to a lack of basic knowledge about viral protein function and protein–protein interactions between viral proteins and between viral and host proteins. In this work, we identified ASFV-ASFV protein–protein interactions (PPIs) using artificial intelligence-powered protein structure prediction tools. We benchmarked our PPI identification workflow on the Vaccinia virus, a widely studied nucleocytoplasmic large DNA virus, and found that it could identify gold-standard PPIs that have been validated in vitro in a genome-wide computational screening. We applied this workflow to more than 18,000 pairwise combinations of ASFV proteins and were able to identify seventeen novel PPIs, many of which have corroborating experimental or bioinformatic evidence for their protein–protein interactions, further validating their relevance. Two protein–protein interactions, I267L and I8L, I267L__I8L, and B175L and DP79L, B175L__DP79L, are novel PPIs involving viral proteins known to modulate host immune response.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2002

Association between simian virus 40 and non-Hodgkin lymphoma

BACKGROUND: Non-Hodgkin lymphoma has increased in frequency over the past 30 years, and is a common cancer in HIV-1-infected patients. Although no definite risk factors have emerged, a viral cause has been postulated. Polyomaviruses are known to infect human beings and to induce tumours in laboratory animals. We aimed to identify which one of the three polyomaviruses able to infect human beings (simian virus 40 [SV40], JC virus, and BK virus) was associated with non-Hodgkin lymphoma. METHODS: We analysed systemic non-Hodgkin lymphoma from 76 HIV-1-infected and 78 HIV-1-uninfected patients, and non-malignant lymphoid samples from 79 HIV-1-positive and 107 HIV-1-negative patients without tumours; 54 colon and breast carcinoma samples served as cancer controls. We used PCR followed by Southern blot hybridisation and DNA sequence analysis to detect DNAs of polyomaviruses and herpesviruses. FINDINGS: Polyomavirus T antigen sequences, all of which were SV40-specific, were detected in 64 (42%) of 154 non-Hodgkin lymphomas, none of 186 non-malignant lymphoid samples, and none of 54 control cancers. This difference was similar for HIV-1-infected patients and HIV-1-uninfected patients alike. Few tumours were positive for both SV40 and Epstein-Barr virus. Human herpesvirus type 8 was not detected. SV40 sequences were found most frequently in diffuse large B-cell and follicular-type lymphomas. INTERPRETATION: SV40 is significantly associated with some types of non-Hodgkin lymphoma. These results add lymphomas to the types of human cancers associated with SV40.

Non-NASA Center↗
DOE OSTI2025

Lassa virus protein–protein interactions as mediators of Lassa fever pathogenesis

Viral hemorrhagic Lassa fever (LF), caused by Lassa virus (LASV), is a significant public health concern endemic in West Africa with high morbidity and mortality rates, limited treatment options, and potential for international spread. Despite advances in interrogating its epidemiology and clinical manifestations, the molecular mechanisms driving pathogenesis of LASV and other arenaviruses remain incompletely understood. This review synthesizes current knowledge regarding the role of LASV host-virus interactions in mediating the pathogenesis of LF, with emphasis on interactions between viral and host proteins. Through investigation of these critical protein–protein interactions, we identify potential therapeutic targets and discuss their implications for development of medical countermeasures including antiviral drugs. This review provides an update in recent literature of significant LASV host-virus interactions important in informing the development of targeted therapies and improving clinical outcomes for LF patients. Knowledge gaps are highlighted as opportunities for future research efforts that would advance the field of LASV and arenavirus pathogenesis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Unique genetic signatures in HIV-1 subtype A1 and A1D recombinant envelope glycoprotein distinguish contemporary transmitted/founder viruses from historical strains in East Africa

Introduction: The envelope glycoprotein (Env) of HIV-1 Transmitted/Founder (T/F) viruses in subtypes B and C carries distinct genetic signatures that enhance transmission fitness, augment infectivity and immune evasion. However, there is limited data on such signatures in T/F subtypes A1, D and A1D recombinants that predominate East Africa’s HIV epidemic.Methods: We used phylogenetically corrected approaches to detect distinct genetic signatures by comparing 44 contemporary HIV-1 T/F Envs with 229 historical Envs of the same subtype in East Africa.Results and Discussion: Subtype analysis based on the full-length Env gene of contemporary T/F viruses revealed a high proportion of subtype A1, followed by A1D recombinants, and fewer subtype D. Signature analysis revealed that the contemporary subtype A1 T/Fs were more likely to select distinct amino acids, including M22 in the signal peptide, R82 in gp120, A172 in the V2 loop, E230 in the glycosite 230, K275 in the D loop, Y317 in the V3 loop, K476 and N477 in the CD4 contact site, when compared with the historical Envs (q-value < 0.2). Conversely, the contemporary subtype A1 T/F Envs were less likely to carry the amino acids Q432 in the CD4 contact site, and the L784 signature within the LLP-2 (q-value < 0.2). The A1D recombinant T/Fs were more likely to select the D620 in the C-helix, but under selected the L34 in gp120, P299 in the V3 loop and Y643 in the Heptad repeat-2, compared to the historical Envs (q-value < 0.2). The distinct signature sites reported in this study may contribute to the successful establishment of acute infection as well as the persistence of long-term infection. Therefore, effective therapeutics and vaccines may target these distinct amino acid signatures especially for the East African region as it may be necessary to employ subtype-specific vaccines according to the subtype distribution.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Molecular Evolution of the H5 and H7 Highly Pathogenic Avian Influenza Virus Haemagglutinin Cleavage Site Motif

ABSTRACT Avian influenza viruses are ubiquitous in the Anatinae subfamily of aquatic birds and occasionally spill over to poultry. Infection with low pathogenicity avian influenza viruses generally leads to subclinical or mild clinical disease. In contrast, highly pathogenic avian influenza viruses emerge from low pathogenic forms and can cause severe disease associated with extraordinarily high mortality rates. Here, we describe the natural history of avian influenza virus, with a focus on H5Nx and H7Nx subtypes, and the emergence of highly pathogenic forms; we review the biology of AIV; we examine cleavage of haemagglutinin by host cell enzymes with a particular emphasis on the biochemical properties of the proprotein convertases, and trypsin and trypsin‐like proteases; we describe mechanisms implicated in the functional evolution of the haemagglutinin cleavage site motif that leads to emergence of HPAIVs; and finally, we discuss the diversity of H5 and H7 haemagglutinin cleavage site sequence motifs. It is crucial to understand the molecular attributes that drive the emergence and evolution of HPAIVs with pandemic potential to inform risk assessments and mitigate the threat of HPAIVs to poultry and human populations.

Luczo, Jasmina M. [Australian Animal Health Labora↗
DOE OSTI2025

Phosphate amendment drives bloom of RNA viruses after soil wet-up

Soil rewetting after a dry period results in a surge of activity and succession in both microbial and DNA virus communities. Less is known about the response of RNA viruses to soil rewetting—while they are highly diverse and widely distributed in soil, they remain understudied. We hypothesized that RNA viruses would show temporal succession following rewetting and that phosphate amendment would influence their trajectory, as viral proliferation may cause phosphorus limitation. Using 39 time-resolved metatranscriptomes and amplicon data, 2190 RNA viral populations were identified across five phyla, with 26 % of these predicted to infect bacteria, and 11 % fungi. Only 1.2 % of viral populations had annotated capsid genes, suggesting most persist via intracellular replication without a free virion phase. Phosphate amendment altered RNA viral community composition within the first week and amended vs. unamended communities remained distinguishable for up to three weeks. While the overall host community remained stable, certain bacterial populations showed reduced abundance in phosphate-amended soils, likely due to increased viral lysis, as RNA bacteriophages proliferated significantly. Notably, 60 % of the viruses with increased abundance under phosphate amendment belonged to basal Lenarviricota clades rather than well-known groups like Leviviricetes. We estimate RNA bacteriophage infections may affect 10 7 –10 9 bacteria per gram of soil, aligning with the total bacterial population (10 7 –10 10 g -1 soil), suggesting that RNA phages significantly influence bacterial communities post-wet-up, with phosphorus availability modulating this effect.

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↗