scholarly journals Diel cycling and long-term persistence of viruses in the ocean’s euphotic zone

2017 ◽  
Vol 114 (43) ◽  
pp. 11446-11451 ◽  
Author(s):  
Frank O. Aylward ◽  
Dominique Boeuf ◽  
Daniel R. Mende ◽  
Elisha M. Wood-Charlson ◽  
Alice Vislova ◽  
...  
Keyword(s):  
Euphotic Zone ◽  
Ecosystem Dynamics ◽  
Viral Gene ◽  
Viral Genomes ◽  
Diel Cycles ◽  
Cellular Replication ◽  
Natural Settings ◽  
Marine Microbial Communities ◽  
Dsdna Viruses

Viruses are fundamental components of marine microbial communities that significantly influence oceanic productivity, biogeochemistry, and ecosystem processes. Despite their importance, the temporal activities and dynamics of viral assemblages in natural settings remain largely unexplored. Here we report the transcriptional activities and variability of dominant dsDNA viruses in the open ocean’s euphotic zone over daily and seasonal timescales. While dsDNA viruses exhibited some fluctuation in abundance in both cellular and viral size fractions, the viral assemblage was remarkably stable, with the most abundant viral types persisting over many days. More extended time series indicated that long-term persistence (>1 y) was the rule for most dsDNA viruses observed, suggesting that both core viral genomes as well as viral community structure were conserved over interannual periods. Viral gene transcription in host cell assemblages revealed diel cycling among many different viral types. Most notably, an afternoon peak in cyanophage transcriptional activity coincided with a peak inProchlorococcusDNA replication, indicating coordinated diurnal coupling of virus and host reproduction. In aggregate, our analyses suggested a tightly synchronized diel coupling of viral and cellular replication cycles in both photoautotrophic and heterotrophic bacterial hosts. A surprising consequence of these findings is that diel cycles in the ocean’s photic zone appear to be universal organizing principles that shape ecosystem dynamics, ecological interactions, and biogeochemical cycling of both cellular and acellular community components.

Recent advances in the analysis full/empty capsid ratio and genome integrity of adeno-associated virus (AAV) gene delivery vectors

2020 ◽  
Vol 20 ◽  
Author(s):  
L. Hajba ◽  
A. Guttman
Keyword(s):  
Gene Delivery ◽  
High Efficiency ◽  
Analytical Techniques ◽  
Viral Gene ◽  
Adeno Associated Virus ◽  
Gene Delivery Vectors ◽  
Empty Capsid ◽  
Purification Methods ◽  
Viral Gene Delivery

: Adeno-associated virus (AAV) is one of the most promising viral gene delivery vectors with long-term gene expression and disease correction featuring high efficiency and excellent safety in human clinical trials. During the production of AAV vectors,there are several quality control (QC)parameters that should be rigorously monitored to comply with clini-cal safety and efficacy. This review gives a short summary of the most frequently used AVV production and purification methods,focusing on the analytical techniques applied to determine the full/empty capsid ratio and the integrity of the encapsidated therapeutic DNA of the products.

scholarly journals Persistent Human Papillomavirus Infection

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 321
Author(s):  
Ashley N. Della Fera ◽  
Alix Warburton ◽  
Tami L. Coursey ◽  
Simran Khurana ◽  
Alison A. McBride
Keyword(s):  
Human Papillomavirus ◽  
Dna Replication ◽  
Cellular Proliferation ◽  
Basal Cells ◽  
Viral Dna ◽  
Viral Dna Replication ◽  
Viral Genomes ◽  
Cellular Environment ◽  
E6 And E7 ◽  
Cellular Replication

Persistent infection with oncogenic human papillomavirus (HPV) types is responsible for ~5% of human cancers. The HPV infectious cycle can sustain long-term infection in stratified epithelia because viral DNA is maintained as low copy number extrachromosomal plasmids in the dividing basal cells of a lesion, while progeny viral genomes are amplified to large numbers in differentiated superficial cells. The viral E1 and E2 proteins initiate viral DNA replication and maintain and partition viral genomes, in concert with the cellular replication machinery. Additionally, the E5, E6, and E7 proteins are required to evade host immune responses and to produce a cellular environment that supports viral DNA replication. An unfortunate consequence of the manipulation of cellular proliferation and differentiation is that cells become at high risk for carcinogenesis.

scholarly journals TRIM22. A Multitasking Antiviral Factor

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1864
Author(s):  
Isabel Pagani ◽  
Guido Poli ◽  
Elisa Vicenzi
Keyword(s):  
Protein Interactions ◽  
Influenza A ◽  
Direct Interaction ◽  
Type I Interferons ◽  
Viral Gene ◽  
Target Cells ◽  
Type I ◽  
Protein Protein Interactions ◽  
Viral Genomes ◽  
Dna And Rna

Viral invasion of target cells triggers an immediate intracellular host defense system aimed at preventing further propagation of the virus. Viral genomes or early products of viral replication are sensed by a number of pattern recognition receptors, leading to the synthesis and production of type I interferons (IFNs) that, in turn, activate a cascade of IFN-stimulated genes (ISGs) with antiviral functions. Among these, several members of the tripartite motif (TRIM) family are antiviral executors. This article will focus, in particular, on TRIM22 as an example of a multitarget antiviral member of the TRIM family. The antiviral activities of TRIM22 against different DNA and RNA viruses, particularly human immunodeficiency virus type 1 (HIV-1) and influenza A virus (IAV), will be discussed. TRIM22 restriction of virus replication can involve either direct interaction of TRIM22 E3 ubiquitin ligase activity with viral proteins, or indirect protein–protein interactions resulting in control of viral gene transcription, but also epigenetic effects exerted at the chromatin level.

Long‐term functional correction of cystathionine β‐synthase deficiency in mice by adeno‐associated viral gene therapy

2021 ◽  
Author(s):  
Hyung‐Ok Lee ◽  
Christiana O. Salami ◽  
Dolan Sondhi ◽  
Stephen M. Kaminsky ◽  
Ronald G. Crystal ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Viral Gene ◽  
Functional Correction ◽  
Viral Gene Therapy

scholarly journals Latently KSHV-Infected Cells Promote Further Establishment of Latency upon Superinfection with KSHV

2021 ◽  
Vol 22 (21) ◽  
pp. 11994
Author(s):  
Chen Gam ze Letova ◽  
Inna Kalt ◽  
Meir Shamay ◽  
Ronit Sarid
Keyword(s):  
Latent Infection ◽  
Fluorescent Proteins ◽  
Cell Types ◽  
Lytic Cycle ◽  
Viral Reservoir ◽  
Virus Spread ◽  
Viral Genomes ◽  
Latently Infected ◽  
Infected Cells

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a cancer-related virus which engages in two forms of infection: latent and lytic. Latent infection allows the virus to establish long-term persistent infection, whereas the lytic cycle is needed for the maintenance of the viral reservoir and for virus spread. By using recombinant KSHV viruses encoding mNeonGreen and mCherry fluorescent proteins, we show that various cell types that are latently-infected with KSHV can be superinfected, and that the new incoming viruses establish latent infection. Moreover, we show that latency establishment is enhanced in superinfected cells compared to primary infected ones. Further analysis revealed that cells that ectopically express the major latency protein of KSHV, LANA-1, prior to and during infection exhibit enhanced establishment of latency, but not cells expressing LANA-1 fragments. This observation supports the notion that the expression level of LANA-1 following infection determines the efficiency of latency establishment and avoids loss of viral genomes. These findings imply that a host can be infected with more than a single viral genome and that superinfection may support the maintenance of long-term latency.

scholarly journals Breaching the Delivery Barrier: Chemical and Physical Airway Epithelium Disruption Strategies for Enhancing Lentiviral-Mediated Gene Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Alexandra McCarron ◽  
Nigel Farrow ◽  
Patricia Cmielewski ◽  
Emma Knight ◽  
Martin Donnelley ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Transfer ◽  
Barrier Properties ◽  
Airway Epithelial Cells ◽  
Viral Gene ◽  
Airway Epithelial ◽  
Expression Levels ◽  
Epithelial Disruption ◽  
Gene Expression Levels

The lungs have evolved complex physical, biological and immunological defences to prevent foreign material from entering the airway epithelial cells. These mechanisms can also affect both viral and non-viral gene transfer agents, and significantly diminish the effectiveness of airway gene-addition therapies. One strategy to overcome the physical barrier properties of the airway is to transiently disturb the integrity of the epithelium prior to delivery of the gene transfer vector. In this study, chemical (lysophosphatidylcholine, LPC) and physical epithelium disruption using wire abrasion were compared for their ability to improve airway-based lentiviral (LV) vector mediated transduction and reporter gene expression in rats. When luciferase expression was assessed at 1-week post LV delivery, LPC airway conditioning significantly enhanced gene expression levels in rat lungs, while a long-term assessment in a separate cohort of rats at 12 months revealed that LPC conditioning did not improve gene expression longevity. In rats receiving physical perturbation to the trachea prior to gene delivery, significantly higher LacZ gene expression levels were found when compared to LPC-conditioned or LV-only control rats when evaluated 1-week post gene transfer. This proof-of-principle study has shown that airway epithelial disruption strategies based on physical perturbation substantially enhanced LV-mediated airway gene transfer in the trachea.

scholarly journals Bacteriophage self-counting in the presence of viral replication

2021 ◽  
Vol 118 (51) ◽  
pp. e2104163118
Author(s):  
Tianyou Yao ◽  
Seth Coleman ◽  
Thu Vu Phuc Nguyen ◽  
Ido Golding ◽  
Oleg A. Igoshin
Keyword(s):  
Gene Expression ◽  
Viral Replication ◽  
Viral Gene Expression ◽  
Host Cells ◽  
Optimal Decision ◽  
Viral Gene ◽  
Viral Genomes ◽  
Viral Copy Number ◽  
Viral Copy ◽  
Type Phage

When host cells are in low abundance, temperate bacteriophages opt for dormant (lysogenic) infection. Phage lambda implements this strategy by increasing the frequency of lysogeny at higher multiplicity of infection (MOI). However, it remains unclear how the phage reliably counts infecting viral genomes even as their intracellular number increases because of replication. By combining theoretical modeling with single-cell measurements of viral copy number and gene expression, we find that instead of hindering lambda’s decision, replication facilitates it. In a nonreplicating mutant, viral gene expression simply scales with MOI rather than diverging into lytic (virulent) and lysogenic trajectories. A similar pattern is followed during early infection by wild-type phage. However, later in the infection, the modulation of viral replication by the decision genes amplifies the initially modest gene expression differences into divergent trajectories. Replication thus ensures the optimal decision—lysis upon single-phage infection and lysogeny at higher MOI.

Streams and Dreams and Cross-site Studies

2016 ◽  
Author(s):  
Sherri L. Johnson
Keyword(s):  
Stream Temperature ◽  
Principal Investigator ◽  
Ecosystem Dynamics ◽  
University Of Oklahoma ◽  
Resource Managers ◽  
Long Term Ecological Research ◽  
Natural Resource Managers ◽  
Heat Budgets ◽  
Postdoctoral Fellowship

The influence of the Long-Term Ecological Research (LTER) program on my science has been to broaden my scope through exposure to long-term research and to encourage me to explore major questions across biomes. Communication and outreach with natural resource managers and policy makers has given me insight into translation of science and shaped my research. Through my experiences in the LTER program, I began collaborations with stream ecologists and biogeochemists across sites, which expanded into a high-profile research project that spanned several decades. I encourage scientists to work at LTER sites because they are supportive science communities with a wealth of information to share. Currently, I am a co–principal investigator at the H. J. Andrews Experimental Forest LTER project (AND) in Oregon and have been involved with LTER sites most of my professional life. In 1990, I began graduate research on freshwater shrimp responses to a hurricane at the Luquillo LTER site (LUQ) with Alan Covich, my PhD advisor at the University of Oklahoma. My involvement with LTER research expanded during my postdoctoral fellowship. Through the LTER All Scientists Meetings, I met Julia Jones and other researchers from AND. With their encouragement, I received a National Science Foundation (NSF) Postdoctoral Fellowship Grant in 1996 to examine stream temperature dynamics at AND. After several years at Oregon State University, I was hired by the US Forest Service (USFS) Pacific Northwest Research Station in 2001 as a USFS scientist for AND and became a co–principal investigator in 2002. I have had the benefit of being mentored for multiple years by Fred Swanson and have gradually assumed lead USFS responsibilities for AND. As a stream ecologist, I have studied basic questions and applied issues involving water quality, water quantity, and stream food webs, primarily in forested streams. My research at the LUQ site has examined responses of fresh water shrimp to disturbances and their role in ecosystem dynamics. At AND, my research exploring patterns and controls of stream temperature began as a theoretical landscape-scale question and expanded to examination of temperature responses to flow paths, calculations of heat budgets, and policy implications of forest management (Johnson and Jones 2000; Johnson 2004).

Optimization of Meniscus Cell Transduction Using Lentivirus and Adeno-Associated Virus for Gene Editing and Tissue Engineering Applications

Cartilage ◽  
2019 ◽  
pp. 194760351988032
Author(s):  
Paolo Arrigoni ◽  
Jacob C. Ruprecht ◽  
Dawn A.D. Chasse ◽  
Katherine A. Glass ◽  
Benjamin Andress ◽  
...  
Keyword(s):  
Gene Editing ◽  
Fluorescent Protein ◽  
Meniscus Repair ◽  
Transduction Efficiency ◽  
Viral Gene ◽  
Isolated Cells ◽  
Adeno Associated Virus ◽  
Meniscus Tissue ◽  
Meniscus Cells

Objectives The utilization of viral vectors to deliver genes of interest directly to meniscus cells and promote long-term modulation of gene expression may prove useful to enhance meniscus repair and regeneration. The objective of this study was to optimize and compare the potential of lentivirus (LV) and adeno-associated virus (AAV) to deliver transgenes to meniscus cells in both intact meniscus tissue and isolated primary cells in monolayer. Design Porcine meniscus tissue explants and primary meniscus cells in monolayer were transduced with LV or self-complementary AAV2 (scAAV2) encoding green fluorescent protein (GFP). Following transduction, explants were enzymatically digested to isolate meniscus cells, and monolayer cells were trypsinized. Isolated cells were analyzed by flow cytometry to determine percent transduction. Results LV and scAAV2 showed a high transduction efficiency in monolayer meniscus cells. scAAV2 was most effective at transducing cells within intact meniscus tissue but the efficiency was less than 20%. Outer zone meniscus cells were more readily transduced by both LV and scAAV2 than the inner zone cells. Higher virus titers and higher cell density resulted in improved transduction efficiency. Polybrene was necessary for the highest transduction efficiency with LV, but it reduced scAAV2 transduction. Conclusions Both LV and scAAV2 efficiently transduce primary meniscus cells but only scAAV2 can modestly transduce cells embedded in meniscus tissue. This work lays the foundation for viral gene transfer to be utilized to deliver bioactive transgenes or gene editing machinery, which can induce long-term and tunable expression of therapeutic proteins from tissue-engineered constructs for meniscus repair and regeneration.

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