scholarly journals Satellite Subgenomic Particles Are Key Regulators of Adeno-Associated Virus Life Cycle

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1185
Author(s):  
Junping Zhang ◽  
Xiangping Yu ◽  
Ping Guo ◽  
Jenni Firrman ◽  
Derek Pouchnik ◽  
...  
Keyword(s):  
Viral Gene Expression ◽  
Viral Gene ◽  
Virus Population ◽  
Molecular Configuration ◽  
Adeno Associated Virus ◽  
Capsid Region ◽  
Double Stranded Rna ◽  
Defective Interfering Particles ◽  
Double Stranded Dna ◽  
Virus Life Cycle

Historically, adeno-associated virus (AAV)-defective interfering particles (DI) were known as abnormal virions arising from natural replication and encapsidation errors. Through single virion genome analysis, we revealed that a major category of DI particles contains a double-stranded DNA genome in a “snapback” configuration. The 5′- snapback genomes (SBGs) include the P5 promoters and partial rep gene sequences. The 3′-SBGs contains the capsid region. The molecular configuration of 5′-SBGs theoretically may allow double-stranded RNA transcription in their dimer configuration. Our studies demonstrated that 5-SBG regulated AAV rep expression and improved AAV packaging. In contrast, 3′-SBGs at its dimer configuration increased levels of cap protein. The generation and accumulation of 5′-SBGs and 3′-SBGs appears to be coordinated to balance the viral gene expression level. Therefore, the functions of 5′-SBGs and 3′-SBGs may help maximize the yield of AAV progenies. We postulate that AAV virus population behaved as a colony and utilizes its subgenomic particles to overcome the size limit of a viral genome and encodes additional essential functions.

scholarly journals Satellite subgenomic particles are key regulators of adeno-associated virus life cycle

2020 ◽  
Author(s):  
Junping Zhang ◽  
Ping Guo ◽  
Xiangping Yu ◽  
Kiwon Lee ◽  
Jenni Firrman ◽  
...  
Keyword(s):  
Viral Gene Expression ◽  
Viral Gene ◽  
Virus Population ◽  
Molecular Configuration ◽  
Adeno Associated Virus ◽  
Capsid Region ◽  
Double Stranded Rna ◽  
Defective Interfering Particles ◽  
Double Stranded Dna ◽  
Virus Life Cycle

AbstractHistorically, AAV defective interfering particles (DI) were known as abnormal virions arising from natural replication and encapsidation errors. Through single virion genome analysis, we revealed that a major category of DI particles contains a double stranded DNA genome in a “snapback” configuration (SBG). The 5’-SBGs include the P5 promoters and partial rep gene sequences. The 3’-SBGs contains the capsid region. The molecular configuration of 5’-SBGs allowed double stranded RNA transcription in their dimer configuration, which in turn regulate AAV rep expression and may improve AAV packaging. In contrast, 3’-SBGs at its dimer configuration increased levels of cap protein. The generation and accumulation of 5’-SBGs and 3’-SBGs appears to be coordinated to balance the viral gene expression level. Therefore, the functions of 5’-SBGs and 3’-SBGs may help maximize the yield of AAV progenies. We postulate that AAV virus population behaved as a colony and utilizes its subgenomic particles to overcome the size limit of viral genome and encodes additional essential functions.

scholarly journals The [KIL-d] Element Specifically Regulates Viral Gene Expression in Yeast

Genetics ◽  
2000 ◽  
Vol 155 (2) ◽  
pp. 601-609 ◽  
Author(s):  
Zsolt Tallóczy ◽  
Rebecca Mazar ◽  
Denise E Georgopoulos ◽  
Fausto Ramos ◽  
Michael J Leibowitz
Keyword(s):  
Gene Expression ◽  
Phenotypic Expression ◽  
Viral Gene Expression ◽  
Virus Genome ◽  
Viral Rna ◽  
High Rate ◽  
Viral Gene ◽  
Double Stranded Rna ◽  
Yeast Prions ◽  
Killer Virus

Abstract The cytoplasmically inherited [KIL-d] element epigenetically regulates killer virus gene expression in Saccharomyces cerevisiae. [KIL-d] results in variegated defects in expression of the M double-stranded RNA viral segment in haploid cells that are “healed” in diploids. We report that the [KIL-d] element is spontaneously lost with a frequency of 10−4–10−5 and reappears with variegated phenotypic expression with a frequency of ≥10−3. This high rate of loss and higher rate of reappearance is unlike any known nucleic acid replicon but resembles the behavior of yeast prions. However, [KIL-d] is distinct from the known yeast prions in its relative guanidinium hydrochloride incurability and independence of Hsp104 protein for its maintenance. Despite its transmissibility by successive cytoplasmic transfers, multiple cytoplasmic nucleic acids have been proven not to carry the [KIL-d] trait. [KIL-d] epigenetically regulates the expression of the M double-stranded RNA satellite virus genome, but fails to alter the expression of M cDNA. This specificity remained even after a cycle of mating and meiosis. Due to its unique genetic properties and viral RNA specificity, [KIL-d] represents a new type of genetic element that interacts with a viral RNA genome.

scholarly journals The [KIL-d] Cytoplasmic Genetic Element of Yeast Results in Epigenetic Regulation of Viral M Double-Stranded RNA Gene Expression

Genetics ◽  
1998 ◽  
Vol 150 (1) ◽  
pp. 21-30 ◽  
Author(s):  
Zsolt Tallóczy ◽  
Sujoy Menon ◽  
Lenore Neigeborn ◽  
Michael J Leibowitz
Keyword(s):  
Gene Expression ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Genetic Trait ◽  
Double Stranded Rna ◽  
Virus Rna ◽  
Nuclear Events ◽  
Rna Genome ◽  
Virus Expression ◽  
Killer Virus

Abstract [KIL-d] is a cytoplasmically inherited genetic trait that causes killer virus-infected cells of Saccharomyces cerevisiae to express the normal killer phenotypes in a/α cells, but to show variegated defective killer phenotypes in a or α type cells. Mating of [KIL-d] haploids results in “healing” of their phenotypic defects, while meiosis of the resulting diploids results in “resetting” of the variegated, but mitotically stable, defects. We show that [KIL-d] does not reside on the double-stranded RNA genome of killer virus. Thus, the [KIL-d] effect on viral gene expression is epigenetic in nature. Resetting requires nuclear events of meiosis, since [KIL-d] can be cytoplasmically transmitted during cytoduction without causing defects in killer virus expression. Subsequently, mating of these cytoductants followed by meiosis generates spore clones expressing variegated defective phenotypes. Cytoduction of wild-type cytoplasm into a phenotypically defective [KIL-d] haploid fails to heal, nor does simultaneous or sequential expression of both MAT alleles cause healing. Thus, healing is not triggered by the appearance of heterozygosity at the MAT locus, but rather requires the nuclear fusion events which occur during mating. Therefore, [KIL-d] appears to interact with the nucleus in order to exert its effects on gene expression by the killer virus RNA genome.

scholarly journals ICTV Virus Taxonomy Profile: Herpesviridae 2021

2021 ◽  
Vol 102 (10) ◽  
Author(s):  
Derek Gatherer ◽  
Daniel P. Depledge ◽  
Carol A. Hartley ◽  
Moriah L. Szpara ◽  
Paola K. Vaz ◽  
...  
Keyword(s):  
Latent Infection ◽  
Severe Disease ◽  
Viral Gene Expression ◽  
International Committee ◽  
Viral Gene ◽  
Complex Structures ◽  
Virus Taxonomy ◽  
Double Stranded Dna ◽  
The Family ◽  
Reptilian Species

Members of the family Herpesviridae have enveloped, spherical virions with characteristic complex structures consisting of symmetrical and non-symmetrical components. The linear, double-stranded DNA genomes of 125–241 kbp contain 70–170 genes, of which 43 have been inherited from an ancestral herpesvirus. In general, herpesviruses have coevolved with and are highly adapted to their hosts, which comprise many mammalian, avian and reptilian species. Following primary infection, they are able to establish lifelong latent infection, during which there is limited viral gene expression. Severe disease is usually observed only in the foetus, the very young, the immunocompromised or following infection of an alternative host. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Herpesviridae, which is available at ictv.global/report/herpesviridae.

scholarly journals Human Cytomegalovirus pUL93 Is Required for Viral Genome Cleavage and Packaging

2015 ◽  
Vol 89 (23) ◽  
pp. 12221-12225 ◽  
Author(s):  
Bernadette M. DeRussy ◽  
Ritesh Tandon
Keyword(s):  
Gene Expression ◽  
Human Cytomegalovirus ◽  
Viral Genome ◽  
Unit Length ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Genome Packaging ◽  
Viral Dna ◽  
Virus Growth ◽  
Virus Life Cycle

Human cytomegalovirus (HCMV) pUL93 is essential for virus growth, but its precise function in the virus life cycle is unknown. Here, we characterize a UL93 stop mutant virus (UL93st-TB40/E-BAC) to demonstrate that the absence of this protein does not restrict viral gene expression; however, cleavage of viral DNA into unit-length genomes as well as genome packaging is abolished. Thus, pUL93 is required for viral genome cleavage and packaging.

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 Gamma Interferon Blocks Gammaherpesvirus Reactivation from Latency

2006 ◽  
Vol 80 (1) ◽  
pp. 192-200 ◽  
Author(s):  
Ashley L. Steed ◽  
Erik S. Barton ◽  
Scott A. Tibbetts ◽  
Daniel L. Popkin ◽  
Mary L. Lutzke ◽  
...  
Keyword(s):  
Immune Surveillance ◽  
Viral Gene Expression ◽  
Gamma Interferon ◽  
Viral Gene ◽  
Herpesvirus Infection ◽  
Murine Gammaherpesvirus ◽  
Ifn Γ ◽  
Gammaherpesvirus 68 ◽  
Novel Strategy

ABSTRACT Establishment of latent infection and reactivation from latency are critical aspects of herpesvirus infection and pathogenesis. Interfering with either of these steps in the herpesvirus life cycle may offer a novel strategy for controlling herpesvirus infection and associated disease pathogenesis. Prior studies show that mice deficient in gamma interferon (IFN-γ) or the IFN-γ receptor have elevated numbers of cells reactivating from murine gammaherpesvirus 68 (γHV68) latency, produce infectious virus after the establishment of latency, and develop large-vessel vasculitis. Here, we demonstrate that IFN-γ is a powerful inhibitor of reactivation of γHV68 from latency in tissue culture. In vivo, IFN-γ controls viral gene expression during latency. Importantly, depletion of IFN-γ in latently infected mice results in an increased frequency of cells reactivating virus. This demonstrates that IFN-γ is important for immune surveillance that limits reactivation of γHV68 from latency.

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