Herpes Simplex Virus Clearance during Purification of a Recombinant Adeno-associated Virus Serotype 1 Vector

2014 ◽  
pp. 150127063140004
Author(s):  
Guo-jie Ye ◽  
Marina M Scotti ◽  
Darby L Thomas ◽  
Lijun Wang ◽  
David R. Knop ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Adeno Associated Virus ◽  
Virus Clearance ◽  
Virus Serotype ◽  
Serotype 1 ◽  
Simplex Virus

Herpes Simplex Virus Clearance During Purification of a Recombinant Adeno-Associated Virus Serotype 1 Vector

2014 ◽  
Vol 25 (4) ◽  
pp. 212-217 ◽  
Author(s):  
Guo-jie Ye ◽  
Marina M. Scotti ◽  
Darby L. Thomas ◽  
Lijun Wang ◽  
David R. Knop ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Adeno Associated Virus ◽  
Virus Clearance ◽  
Virus Serotype ◽  
Serotype 1 ◽  
Simplex Virus

scholarly journals 470. Efficient Clearance of Herpes Simplex Virus Using a GMP-Compliant Method for Production of Recombinant Adeno-Associated Virus Vectors

2015 ◽  
Vol 23 ◽  
pp. S186-S187
Author(s):  
Guo-jie Ye ◽  
Chantelle Gaskin ◽  
Charlotte Butts ◽  
Royce Threadgill ◽  
David R. Knop ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Adeno Associated Virus ◽  
Virus Vectors ◽  
Simplex Virus

scholarly journals Adeno-Associated Virus Type 2 Rep68 Can Bind to Consensus Rep-Binding Sites on the Herpes Simplex Virus 1 Genome

2015 ◽  
Vol 89 (21) ◽  
pp. 11150-11158 ◽  
Author(s):  
Michael Seyffert ◽  
Daniel L. Glauser ◽  
Kurt Tobler ◽  
Oleg Georgiev ◽  
Rebecca Vogel ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Binding Sites ◽  
Herpes Simplex Virus 1 ◽  
Adeno Associated Virus ◽  
Binding Domains ◽  
Simplex Virus ◽  
Hsv 1

Adeno-associated virus type 2 is known to inhibit replication of herpes simplex virus 1 (HSV-1). This activity has been linked to the helicase- and DNA-binding domains of the Rep68/Rep78 proteins. Here, we show that Rep68 can bind to consensus Rep-binding sites on the HSV-1 genome and that the Rep helicase activity can inhibit replication of any DNA if binding is facilitated. Therefore, we hypothesize that inhibition of HSV-1 replication involves direct binding of Rep68/Rep78 to the HSV-1 genome.

scholarly journals Identification of Rep-Associated Factors in Herpes Simplex Virus Type 1-Induced Adeno-Associated Virus Type 2 Replication Compartments

2010 ◽  
Vol 84 (17) ◽  
pp. 8871-8887 ◽  
Author(s):  
Armel Nicolas ◽  
Nathalie Alazard-Dany ◽  
Coline Biollay ◽  
Loredana Arata ◽  
Nelly Jolinon ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Particle Production ◽  
Helper Virus ◽  
Adeno Associated Virus ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Adeno-associated virus (AAV) is a human parvovirus that replicates only in cells coinfected with a helper virus, such as adenovirus or herpes simplex virus type 1 (HSV-1). We previously showed that nine HSV-1 factors are able to support AAV rep gene expression and genome replication. To elucidate the strategy of AAV replication in the presence of HSV-1, we undertook a proteomic analysis of cellular and HSV-1 factors associated with Rep proteins and thus potentially recruited within AAV replication compartments (AAV RCs). This study resulted in the identification of approximately 60 cellular proteins, among which factors involved in DNA and RNA metabolism represented the largest functional categories. Validation analyses indicated that the cellular DNA replication enzymes RPA, RFC, and PCNA were recruited within HSV-1-induced AAV RCs. Polymerase δ was not identified but subsequently was shown to colocalize with Rep within AAV RCs even in the presence of the HSV-1 polymerase complex. In addition, we found that AAV replication is associated with the recruitment of components of the Mre11/Rad50/Nbs1 complex, Ku70 and -86, and the mismatch repair proteins MSH2, -3, and -6. Finally, several HSV-1 factors were also found to be associated with Rep, including UL12. We demonstrated for the first time that this protein plays a role during AAV replication by enhancing the resolution of AAV replicative forms and AAV particle production. Altogether, these analyses provide the basis to understand how AAV adapts its replication strategy to the nuclear environment induced by the helper virus.

scholarly journals Herpes simplex virus serotype and entry receptor availability alter CNS disease in a mouse model of neonatal HSV

2014 ◽  
Vol 76 (6) ◽  
pp. 528-534 ◽  
Author(s):  
Sarah J. Kopp ◽  
Hantamalala R. Ranaivo ◽  
Douglas R. Wilcox ◽  
Andrew H. Karaba ◽  
Mark S. Wainwright ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Mouse Model ◽  
Cns Disease ◽  
Virus Serotype ◽  
Simplex Virus ◽  
Entry Receptor

scholarly journals Herpes Simplex Virus Type 1/Adeno-Associated Virus rep+ Hybrid Amplicon Vector Improves the Stability of Transgene Expression in Human Cells by Site-Specific Integration

2002 ◽  
Vol 76 (14) ◽  
pp. 7150-7162 ◽  
Author(s):  
Y. Wang ◽  
S. M. Camp ◽  
M. Niwano ◽  
X. Shen ◽  
J. C. Bakowska ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Transgene Expression ◽  
Adeno Associated Virus ◽  
Site Specific ◽  
Site Specific Integration ◽  
Primary Myoblasts ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Herpes simplex virus type 1 (HSV-1) amplicon vectors are promising gene delivery tools, but their utility in gene therapy has been impeded to some extent by their inability to achieve stable transgene expression. In this study, we examined the possibility of improving transduction stability in cultured human cells via site-specific genomic integration mediated by adeno-associated virus (AAV) Rep and inverted terminal repeats (ITRs). A rep − HSV/AAV hybrid amplicon vector was made by inserting a transgene cassette flanked with AAV ITRs into an HSV-1 amplicon backbone, and a rep + HSV/AAV hybrid amplicon was made by inserting rep68/78 outside the rep − vector 3′ AAV ITR sequence. Both vectors also had a pair of loxP sites flanking the ITRs. The resulting hybrid amplicon vectors were successfully packaged and compared to a standard amplicon vector for stable transduction frequency (STF) in human 293 and Gli36 cell lines and primary myoblasts. The rep +, but not the rep −, hybrid vector improved STF in all three types of cells; 84% of Gli36 and 40% of 293 stable clones transduced by the rep + hybrid vector integrated the transgene into the AAVS1 site. Due to the difficulty in expanding primary myoblasts, we did not assess site-specific integration in these cells. A strategy to attempt further improvement of STF by “deconcatenating” the hybrid amplicon DNA via Cre-loxP recombination was tested, but it did not increase STF. These data demonstrate that introducing the integrating elements of AAV into HSV-1 amplicon vectors can significantly improve their ability to achieve stable gene transduction by conferring the AAV-like capability of site-specific genomic integration in dividing cells.

scholarly journals Combinations of Antiviral and Anti-Inflammatory Preparations for the Topical Treatment of Herpes Simplex Virus Assessed using a Murine Zosteriform Infection Model

1998 ◽  
Vol 9 (1) ◽  
pp. 19-24 ◽  
Author(s):  
AR Awan ◽  
J Harmenberg ◽  
O Flink ◽  
HJ Field
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Replication ◽  
Immune Cells ◽  
Clinical Signs ◽  
Infection Model ◽  
Virus Clearance ◽  
Anti Inflammatory ◽  
Simplex Virus ◽  
Hsv 1

Recently we have reported a zosteriform murine infection model which employs the adoptive transfer of immune cells (ATI) to recipient infected mice to produce a disease that mimics human recurrent herpes simplex virus (HSV) disease. Mice were infected with HSV-1 by scarification at the lateroventral line of the neck; 2 days later, the mice received immune cells from HSV-1-infected syngeneic mice. Although virus was cleared more quickly from the target tissues of virus replication in recipient mice, ATI resulted in a heightened inflammatory response and delayed healing. This model was used to test the effects of topical formulations containing foscarnet and/or the anti-inflammatory agent, hydrocortisone. Virus clearance and clinical signs, including ear thickness and zosteriform spread of lesions, were studied. Treatment with 3% foscarnet accelerated virus clearance but had little effect on clinical parameters. By contrast, 0.5% hydrocortisone increased the titre and extended the presence of infectious virus for at least 6 days, although the reduction in clinical signs was greater than that obtained with topical foscarnet. Foscarnet in combination with hydrocortisone produced a marked reduction in clinical signs while virus replication was reduced. These results are discussed in relation to the inflammation and discomfort experienced by patients and a possible role for anti-inflammatory formulations in the treatment of HSV reactivation episodes in man.

scholarly journals Herpes Simplex Virus Type 1 Co-Infection Modifies Adeno-Associated Virus Genome End Recombination

2021 ◽  
Author(s):  
Anita Felicitas Meier ◽  
Kurt Tobler ◽  
Kevin Michaelsen ◽  
Bernd Vogt ◽  
Els Henckaerts ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Molecular Structures ◽  
Adeno Associated Virus ◽  
Genome Recombination ◽  
Simplex Virus ◽  
Hsv 1

Wildtype adeno-associated virus (AAV) can only replicate in the presence of helper factors, which can be provided by co-infecting helper viruses such as adenoviruses and herpes viruses. The AAV genome consists of a linear, single-stranded DNA (ssDNA), which is converted into different molecular structures within the host cell. Using high throughput sequencing we found that herpes simplex virus type 1 (HSV-1) co-infection leads to a shift in the type of AAV genome end recombination. In particular, open-end ITR recombination was enhanced whereas open-closed ITR recombination was reduced in the presence of HSV-1. We demonstrate that the HSV-1 protein ICP8 plays an essential role in HSV-1 mediated interference with AAV genome end recombination, indicating that the previously described ICP8-driven mechanism of HSV-1 genome recombination may be underlying the observed changes. We also provide evidence that additional factors, such as products of true late genes, are involved. Although HSV-1 co-infection significantly changed the type of AAV genome end recombination, no significant change in the amount of circular AAV genomes was identified. IMPORTANCE AAV-mediated gene therapy represents one of the most promising approaches for the treatment of genetic diseases. Currently, various GMP-compatible production methods can be applied to manufacture clinical grade vector, including methods that employ helper factors derived form HSV-1. Yet to date we do not fully understand how HSV-1 interacts with AAV. We observed that HSV-1 modulates AAV genome ends similarly to the genome recombination events observed during HSV-1 replication and postulate that further improvements of the HSV-1 production platform may enhance packaging of the recombinant AAV particles.

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