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Viruses Jun 2020The adeno-associated virus (AAV) is a small, nonpathogenic parvovirus, which depends on helper factors to replicate. Those helper factors can be provided by coinfecting... (Review)
Review
The adeno-associated virus (AAV) is a small, nonpathogenic parvovirus, which depends on helper factors to replicate. Those helper factors can be provided by coinfecting helper viruses such as adenoviruses, herpesviruses, or papillomaviruses. We review the basic biology of AAV and its most-studied helper viruses, adenovirus type 5 (AdV5) and herpes simplex virus type 1 (HSV-1). We further outline the direct and indirect interactions of AAV with those and additional helper viruses.
Topics: Adenoviridae; Coinfection; Dependovirus; Helper Viruses; Herpesvirus 1, Human; Humans; Parvoviridae Infections; Viral Proteins; Virus Replication
PubMed: 32575422
DOI: 10.3390/v12060662 -
BMB Reports Nov 2020Gene therapy is emerging as a treatment option for inherited genetic diseases. The success of this treatment approach greatly depends upon gene delivery vectors.... (Review)
Review
Gene therapy is emerging as a treatment option for inherited genetic diseases. The success of this treatment approach greatly depends upon gene delivery vectors. Researchers have attempted to harness the potential of viral vectors for gene therapy applications over many decades. Among the viral vectors available, gutless adenovirus (GLAd) has been recognized as one of the most promising vectors for in vivo gene delivery. GLAd is constructed by deleting all the viral genes from an adenovirus. Owing to this structural feature, the production of GLAd requires a helper that supplies viral proteins in trans. Conventionally, the helper is an adenovirus. Although the helper adenovirus efficiently provides helper functions, it remains as an unavoidable contaminant and also generates replicationcompetent adenovirus (RCA) during the production of GLAd. These two undesirable contaminants have raised safety concerns and hindered the clinical applications of GLAd. Recently, we developed helper virus-free gutless adenovirus (HF-GLAd), a new version of GLAd, which is produced by a helper plasmid instead of a helper adenovirus. Utilization of this helper plasmid eliminated the helper adenovirus and RCA contamination in the production of GLAd. HF-GLAd, devoid of helper adenovirus and RCA contaminants, will facilitate its clinical applications. In this review, we discuss the characteristics of adenoviruses, the evolution and production of adenoviral vectors, and the unique features of HF-GLAd as a new platform for gene therapy. Furthermore, we highlight the potential applications of HF-GLAd as a gene delivery vector for the treatment of various inherited genetic diseases. [BMB Reports 2020; 53(11): 565-575].
Topics: Adenoviridae; Cell Line; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Helper Viruses; Humans; Integrases; Plasmids; Viral Proteins
PubMed: 32958121
DOI: 10.5483/BMBRep.2020.53.11.185 -
Current Gene Therapy Jun 2005The human parvovirus Adeno-Associated virus (AAV-2) has been classified as a Dependovirus because it requires the presence of a helper virus to achieve a productive... (Review)
Review
The human parvovirus Adeno-Associated virus (AAV-2) has been classified as a Dependovirus because it requires the presence of a helper virus to achieve a productive replication cycle. Several viruses such as Adenovirus (Ad), Herpes Simplex Virus (HSV), Vaccinia virus, and human papillomaviruses (HPV) can provide the helper activities required for AAV growth. The studies on the helper activities provided by adenovirus have provided useful information not only to understand the AAV-2 biology but also to develop tools for the production of recombinant AAV particles (rAAV). This review will focus on the current knowledge about the helper activities provided by the most extensively studied helper viruses, Ad and HSV-1, and also illustrate the methods used to supply the helper functions rAAV assembly.
Topics: Dependovirus; Genetic Therapy; Helper Viruses; Humans; Parvovirus
PubMed: 15975004
DOI: 10.2174/1566523054064977 -
Experimental Neurology Mar 1997Vectors based on herpes simplex virus type 1 (HSV-1) have potential for gene therapy of neurological disorders. HSV-1 plasmid vectors (amplicons) contain only... (Review)
Review
Vectors based on herpes simplex virus type 1 (HSV-1) have potential for gene therapy of neurological disorders. HSV-1 plasmid vectors (amplicons) contain only approximately 1% of the 150-kb HSV-1 genome and have been packaged into virus particles by using a helper virus. We have demonstrated that HSV-1 plasmid vectors which express tyrosine hydroxylase can cause long-term biochemical and behavioral recovery in the 6-hydroxydopamine rat model of Parkinson's disease. Furthermore, we and others have used HSV-1 plasmid vectors which express a wide range of genes that affect neuronal physiology. Because of the pathogenicity of the HSV-1 helper virus, however, the use of this vector system has been limited to studies in animal models or primary cultures of neural cells. Thus, to increase the safety of HSV-1 plasmid vectors, we recently developed a helper virus-free packaging system that may facilitate studies on neuronal physiology and potential therapeutic applications.
Topics: Animals; Genetic Therapy; Genetic Vectors; Helper Viruses; Herpesvirus 1, Human; Humans; Nervous System Diseases; Parkinson Disease; Plasmids
PubMed: 9126158
DOI: 10.1006/exnr.1996.6394 -
Viruses Jun 2021Hepatitis delta virus (HDV) is a defective human virus that lacks the ability to produce its own envelope proteins and is thus dependent on the presence of a helper... (Review)
Review
Hepatitis delta virus (HDV) is a defective human virus that lacks the ability to produce its own envelope proteins and is thus dependent on the presence of a helper virus, which provides its surface proteins to produce infectious particles. Hepatitis B virus (HBV) was so far thought to be the only helper virus described to be associated with HDV. However, recent studies showed that divergent HDV-like viruses could be detected in fishes, birds, amphibians, and invertebrates, without evidence of any HBV-like agent supporting infection. Another recent study demonstrated that HDV can be transmitted and propagated in experimental infections ex vivo and in vivo by different enveloped viruses unrelated to HBV, including hepatitis C virus (HCV) and flaviviruses such as Dengue and West Nile virus. All this new evidence, in addition to the identification of novel virus species within a large range of hosts in absence of HBV, suggests that deltaviruses may take advantage of a large spectrum of helper viruses and raises questions about HDV origins and evolution.
Topics: Animals; Evolution, Molecular; Genome, Viral; Helper Viruses; Hepatitis D; Hepatitis Delta Virus; Host Specificity; Humans; Phylogeny; Viral Proteins; Virus Replication
PubMed: 34201626
DOI: 10.3390/v13071207 -
Human Gene Therapy Nov 1998Retroviral vectors based on human foamy virus (HFV) have been developed and show promise as gene therapy vehicles. Here we describe a method for the production of HFV...
Retroviral vectors based on human foamy virus (HFV) have been developed and show promise as gene therapy vehicles. Here we describe a method for the production of HFV vector stocks free of detectable helper virus. The helper and vector plasmid constructs used both lack the HFV bel genes, so recombination between these constructs cannot create a wild-type virus. A fusion promoter that combines portions of the cytomegalovirus (CMV) immediate-early and HFV long terminal repeat (LTR) promoters was used to drive expression of both the helper and vector constructs. The CMV-LTR fusion promoter allows for HFV vector production in the absence of the Bel-1 trans-activator protein, which would otherwise be necessary for efficient transcription from the HFV LTR. Vector stocks containing either neomycin phosphotransferase or alkaline phosphatase reporter genes were produced by transient transfection at titers greater than 10(5) transducing units/ml. G418-resistant BHK-21 cells obtained by transduction with neo vectors contained randomly integrated HFV vector proviruses without detectable deletions or rearrangements. The vector stocks generated were free of replication-competent retrovirus (RCR), as determined by assays for LTR trans-activation and a marker rescue assay developed here for the detection of Bel-independent RCR.
Topics: Base Sequence; DNA Primers; Genetic Vectors; Helper Viruses; Humans; Spumavirus; Virus Replication
PubMed: 9853518
DOI: 10.1089/hum.1998.9.17-2517 -
Phytopathology May 2024Sugar beet () is grown in temperate regions around the world as a source of sucrose used for natural sweetening. Sugar beet is susceptible to a number of viral diseases,...
Sugar beet () is grown in temperate regions around the world as a source of sucrose used for natural sweetening. Sugar beet is susceptible to a number of viral diseases, but identification of the causal agent(s) under field conditions is often difficult due to mixtures of viruses that may be responsible for disease symptoms. In this study, the application of RNAseq to RNA extracted from diseased sugar beet roots obtained from the field and from greenhouse-reared plants grown in soil infested with the virus disease rhizomania (causal agent beet necrotic yellow vein virus; BNYVV) yielded genome-length sequences from BNYVV, as well as beet soil-borne virus (BSBV). The nucleotide identities of the derived consensus sequence of BSBV RNAs ranged from 99.4 to 96.7% (RNA1), 99.3 to 95.3% (RNA2), and 98.3 to 95.9% (RNA3) compared with published BSBV sequences. Based on the BSBV genome consensus sequence, clones of the genomic RNAs 1, 2, and 3 were obtained to produce RNA copies of the genome through in vitro transcription. Capped RNA produced from the clones was infectious when inoculated into leaves of and , and extracts from transcript-infected leaves could infect sugar beet seedling roots through a vortex inoculation method. Subsequent exposure of these infected sugar beet seedling roots to aviruliferous , the protist vector of both BNYVV and BSBV, confirmed that BSBV derived from the infectious clones could be transmitted by the vector. Co-inoculation of BSBV synthetic transcripts with transcripts of a cloned putative satellite virus designated Beta vulgaris satellite virus 1A (BvSat1A) resulted in the production of lesions on leaves of similar to those produced by inoculation with BSBV alone. Nevertheless, accumulation of genomic RNA and the encoded protein of the satellite virus in co-inoculated leaves was readily detected on Northern and Western blots, respectively, whereas no accumulation of satellite virus products occurred when satellite virus RNA was inoculated alone. The predicted sequence of the detected protein encoded by BvSat1A bears hallmarks of coat proteins of other satellite viruses, and virions of a size consistent with a satellite virus were observed in samples testing positive for the virus. The results demonstrate that BSBV is a helper virus for the novel satellite virus BvSat1A.
Topics: Beta vulgaris; Plant Diseases; Satellite Viruses; Plant Viruses; Helper Viruses; RNA, Viral; Plant Roots; Genome, Viral; Soil Microbiology
PubMed: 38451582
DOI: 10.1094/PHYTO-08-23-0299-KC -
Current Protocols in Molecular Biology Feb 2005The helper-dependent adenovirus (HDAd) is a recently developed adenovirus-based vector with an improved safety profile and long-term transgene expression. In this unit,...
The helper-dependent adenovirus (HDAd) is a recently developed adenovirus-based vector with an improved safety profile and long-term transgene expression. In this unit, a basic procedure for HDAd production using the Cre-loxP system is presented. Amplification and large-scale production of the vector can be done in both adherent and suspension cell culture systems. Included are protocols for Southern blot analysis to monitor vector amplification, slot blot assay to determine the infectious titer of the purified HDAd, and real-time PCR to detect helper virus contamination in the preparation.
Topics: Adenoviridae; Genetic Techniques; Genetic Vectors; Helper Viruses; Integrases; Virus Replication
PubMed: 18265354
DOI: 10.1002/0471142727.mb1624s69 -
Current Protocols in Neuroscience Jul 2012Herpes simplex virus type 1 (HSV-1)-based amplicon vectors contain only a very small percentage of the 152-kbp viral genome. Consequently, replication and packaging of...
Herpes simplex virus type 1 (HSV-1)-based amplicon vectors contain only a very small percentage of the 152-kbp viral genome. Consequently, replication and packaging of amplicons depend on helper functions that are provided either by replication-defective mutants of HSV-1 or by replication-competent, but packaging-defective, HSV-1 genomes. Sets of cosmids that overlap and represent the entire HSV-1 genome can form, via homologous recombination, circular replication-competent viral genomes, which give rise to infectious virus progeny. However, if the DNA cleavage/packaging signals are deleted, reconstituted virus genomes are not packageable, but still provide all the helper functions required for the packaging of cotransfected amplicon DNA. The resulting stocks of packaged amplicon vectors are essentially free of contaminating helper virus. This unit describes the cotransfection of amplicon and cosmid or bacterial artificial chromosome (BAC) DNA into 2-2 cells by cationic liposome-mediated transfection and the harvesting of packaged vector particles. Support protocols provide methods for preparing cosmid and BAC DNA and determining the titers of amplicon stocks.
Topics: Animals; Escherichia coli; Gene Transfer Techniques; Genetic Vectors; Helper Viruses; Herpesvirus 1, Human; Humans; Transfection; Virus Replication
PubMed: 22752894
DOI: 10.1002/0471142301.ns0414s60 -
Virus Genes Jun 2001Many retroviruses that carry oncogenes (acute transforming viruses) are generally replication-defective and therefore require co-infection with a replication competent...
Many retroviruses that carry oncogenes (acute transforming viruses) are generally replication-defective and therefore require co-infection with a replication competent 'helper' retrovirus for infectivity. The helper virus provides the retroviral proteins necessary for particle production and infection. These include the envelope glycoproteins that specifically bind to cell surface receptors and mediate viral adsorption and entry. Thus, a particular helper virus may influence the nature of disease induced by an oncogene-containing retrovirus due to tissue tropism of the helper. In a previous study, a replication-defective recombinant Moloney murine leukemia virus containing the v-myc oncogene was generated (M-MuLV(myc); Brightman B.K., Pattengale P.K., and Fan H., J Virol 60: 68-81, 1986). When M-MuLV(myc) was inoculated into mice using the non-pathogenic amphotropic murine leukemia virus (Am-MuLV 4070) as a helper, T- and B-lymphoblastic lymphomas resulted with the following two surface phenotypes, namely, (1) Thy 1.2+, B220- and (2) Thy 1.2-, B220+. Thy 1.2 surface antigen is characteristic of cells of the lymphoid lineage, whereas B220 surface antigen is characteristic of cells of the B-lymphoid lineage. In these experiments, to assess the influence of the helper virus on the disease specificity of M-MuLV(myc), two weakly pathogenic ecotropic helper MuLVs that interact with different cell surface receptors than Am-MuLV (Mo+PyF101 and AKV MuLV) were used to pseudotype M-MuLV(myc). In both cases, when inoculated into mice, these pseudotypes induced only T-lymphoblastic lymphoma. These results indicate that for M-MuLV(myc) the types of the tumors induced are influenced by the helper virus utilized, and they suggest that different lymphoid cells may express different levels of retroviral receptors.
Topics: Animals; Blotting, Southern; DNA, Neoplasm; Fluorescent Antibody Technique; Genes, myc; Helper Viruses; Leukemia Virus, Murine; Lymphoma, B-Cell; Lymphoma, T-Cell; Membrane Glycoproteins; Mice; Tumor Cells, Cultured; Viral Envelope Proteins
PubMed: 11450949
DOI: 10.1023/a:1011166323566