scholarly journals Adeno-Associated Viruses Can Induce Phosphorylation of eIF2α via PKR Activation, Which Can Be Overcome by Helper Adenovirus Type 5 Virus-Associated RNA

2007 ◽  
Vol 81 (21) ◽  
pp. 11908-11916 ◽  
Author(s):  
Ramnath Nayak ◽  
David J. Pintel
Keyword(s):  
Cellular Response ◽  
Adenovirus Type ◽  
Capsid Gene ◽  
Protein Accumulation ◽  
Protein Kinase R ◽  
Adeno Associated Virus ◽  
Simplex Virus ◽  
Rna I ◽  
Interfering Rna ◽  
Adenovirus Type 5

ABSTRACT Mutants of adenovirus type 5 (Ad5) virus-associated RNA I deficient in inhibiting the activation and subsequent phosphorylation of protein kinase R (PKR) could neither function as helpers for adeno-associated virus type 5 (AAV5) replication nor enhance AAV5 protein accumulation in either the presence or absence of Ad5 E4Orf6 and E2a. Furthermore, a short region of the AAV5 capsid gene RNA leader sequence surrounding the AUG of VP1 could induce the phosphorylation of eIF2α. Both short interfering RNA directed against PKR and the addition of the herpes simplex virus ICP34.5 protein enhanced the accumulation of AAV5 capsid protein in the presence of the AAV5 capsid gene PKR-inducing element, suggesting that VA RNA acted to overcome direct AAV5-induced activation of PKR that led to the phosphorylation of eIF2α. The expression of both the closely related goat-derived AAV and the prototype AAV2 capsid gene transcription units also induced the phosphorylation of eIF2α, suggesting that the induction of the PKR/eIF2α cellular response may be a previously unrecognized general feature of at least the Dependovirus genus of the Parvovirinae.

scholarly journals Positive and Negative Effects of Adenovirus Type 5 Helper Functions on Adeno-Associated Virus Type 5 (AAV5) Protein Accumulation Govern AAV5 Virus Production

2006 ◽  
Vol 81 (5) ◽  
pp. 2205-2212 ◽  
Author(s):  
Ramnath Nayak ◽  
David J. Pintel
Keyword(s):  
Virus Type ◽  
De Novo ◽  
Virus Production ◽  
Adenovirus Type ◽  
Protein Accumulation ◽  
Dependent Manner ◽  
Negative Effects ◽  
Adeno Associated Virus ◽  
Individual Effects ◽  
Adenovirus Type 5

ABSTRACT Full replication of adeno-associated virus type 5 (AAV5) is sustained by adenovirus type 5 (Ad5) helper functions E1a, E1b, E2a, E4Orf6, and virus-associated (VA) RNA; however, their combined net enhancement of AAV5 replication was comprised of both positive and negative individual effects. Although Ad5 E4Orf6 was required for AAV5 genomic DNA replication, it also functioned together with E1b to degrade de novo-expressed, preassembled AAV5 capsid proteins and Rep52 in a proteosome-dependent manner. VA RNA enhanced accumulation of AAV5 protein, overcoming the degradative effects of E4Orf6, and was thus required to restore adequate amounts of AAV5 proteins necessary to achieve efficient virus production.

scholarly journals Adeno-Associated Virus Small Rep Proteins Are Modified with at Least Two Types of Polyubiquitination

2009 ◽  
Vol 84 (2) ◽  
pp. 1206-1211 ◽  
Author(s):  
K. David Farris ◽  
Olufemi Fasina ◽  
Loretta Sukhu ◽  
Long Li ◽  
David J. Pintel
Keyword(s):  
Small Interfering Rna ◽  
Adenovirus Type ◽  
Proteasomal Degradation ◽  
Transient Transfection ◽  
Adeno Associated Virus ◽  
Rep Proteins ◽  
Cullin 5 ◽  
Interfering Rna ◽  
Adenovirus Type 5

ABSTRACT Adeno-associated virus (AAV) type 2 and 5 proteins Rep52 and Rep40 were polyubiquitinated during AAV-adenovirus type 5 (Ad5) coinfection and during transient transfection in either the presence or absence of Ad5 E4orf6 and E1b-55k. Polyubiquitination of small Rep proteins via lysine 48 (K48) linkages, normally associated with targeting of proteins for proteasomal degradation, was detected only in the presence of E4orf6. The small Rep proteins were ubiquitinated via lysine 63 (K63) following transfection in either the presence or absence of E4orf6 or following coinfection with Ad5. E4orf6/E1b-55k-dependent K48-specific polyubiquitination of small Rep proteins could be inhibited using small interfering RNA (siRNA) to cullin 5.

scholarly journals The Interplay between Adeno-Associated Virus and Its Helper Viruses

Viruses ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 662 ◽  
Author(s):  
Anita F. Meier ◽  
Cornel Fraefel ◽  
Michael Seyffert
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Adenovirus Type ◽  
Adeno Associated Virus ◽  
Basic Biology ◽  
Simplex Virus ◽  
Adenovirus Type 5

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.

A study of possible biohazards in the fluorescent antibody test using adenovirus, coxsackievirus, herpesvirus, and respiratory syncytial virus as antigens

1976 ◽  
Vol 4 (4) ◽  
pp. 322-325
Author(s):  
D Bardell
Keyword(s):  
Respiratory Syncytial Virus ◽  
Infectious Virus ◽  
Fluorescent Antibody ◽  
Antibody Test ◽  
Adenovirus Type ◽  
Antigenic Determinants ◽  
Syncytial Virus ◽  
Simplex Virus ◽  
Adenovirus Type 5

Infectious adenovirus type 5 and coxsackievirus type B5, both nonlipid-containing viruses, were isolated from cells fixed in acetone at 22 degrees C for 15 min, from acetone used for fixation, from the solution used for washing slides during the fluorescent antibody procedure, and after complete processing of antigen preparations with serial twofold dilutions of human antisera and fluorescein-labeled goat anti-human immunoglobulin G. Lipid-containing herpes simplex virus type 1 and respiratory syncytial virus were inactivated by acetone, and infectious virus could not be recovered at any stage in the fluorescent antibody test. Fixation in acetone at 56 degrees C destroyed the infectivity of adenovirus 5 and coxsackievirus B5 within 30 min, but no adverse effect on the antigenic determinants of either virus occurred until after 60 min, thus demonstrating that these antigens can be utilized without the hazard of infectious virus.

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