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Adeno-associated Virus Vectors Efficiently Transduce Mouse and Rabbit Sensory Neurons Coinfected with Herpes Simplex Virus 1 following Peripheral Inoculation.
Watson, Zachary L; Ertel, Monica K; Lewin, Alfred S; Tuli, Sonal S; Schultz, Gregory S; Neumann, Donna M; Bloom, David C.
Afiliação
  • Watson ZL; Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA.
  • Ertel MK; Department of Pharmacology and Experimental Therapeutics Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
  • Lewin AS; Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA.
  • Tuli SS; Department of Ophthalmology, University of Florida College of Medicine, Gainesville, Florida, USA.
  • Schultz GS; Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, Florida, USA.
  • Neumann DM; Department of Pharmacology and Experimental Therapeutics Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
  • Bloom DC; Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA dbloom@ufl.edu.
J Virol ; 90(17): 7894-901, 2016 09 01.
Article em En | MEDLINE | ID: mdl-27334582
ABSTRACT
UNLABELLED Following infection of epithelial tissues, herpes simplex virus 1 (HSV-1) virions travel via axonal transport to sensory ganglia and establish a lifelong latent infection within neurons. Recent studies have revealed that, following intraganglionic or intrathecal injection, recombinant adeno-associated virus (rAAV) vectors can also infect sensory neurons and are capable of stable, long-term transgene expression. We sought to determine if application of rAAV to peripheral nerve termini at the epithelial surface would allow rAAV to traffic to sensory ganglia in a manner similar to that seen with HSV. We hypothesized that footpad or ocular inoculation with rAAV8 would result in transduction of dorsal root ganglia (DRG) or trigeminal ganglia (TG), respectively. To test this, we inoculated the footpads of mice with various amounts of rAAV as well as rAAV capsid mutants. We demonstrated that this method of inoculation can achieve a transduction rate of >90% of the sensory neurons in the DRG that innervate the footpad. Similarly, we showed that corneal inoculation with rAAV vectors in the rabbit efficiently transduced >70% of the TG neurons in the optic tract. Finally, we demonstrated that coinfection of mouse footpads or rabbit eyes with rAAV vectors and HSV-1 resulted in colocalization in nearly all of the HSV-1-positive neurons. These results suggest that rAAV is a useful tool for the study of HSV-1 infection and may provide a means to deliver therapeutic cargos for the treatment of HSV infections or of dysfunctions of sensory ganglia. IMPORTANCE Adeno-associated virus (AAV) has been shown to transduce dorsal root ganglion sensory neurons following direct intraganglionic sciatic nerve injection and intraperitoneal and intravenous injection as well as intrathecal injection. We sought to determine if rAAV vectors would be delivered to the same sensory neurons that herpes simplex virus (HSV-1) infects when applied peripherally at an epithelial surface that had been treated to expose the underlying sensory nerve termini. For this study, we chose two well-established HSV-1 infection models mouse footpad infection and rabbit ocular infection. The results presented here provide the first description of AAV vectors transducing neurons following delivery at the skin/epithelium/eye. The ability of AAV to cotransduce HSV-1-infected neurons in both the mouse and the rabbit provides an opportunity to experimentally explore and disrupt host and viral proteins that are integral to the establishment of HSV-1 latency, to the maintenance of latency, and to reactivation from latency in vivo.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Receptoras Sensoriais / Transdução Genética / Herpesvirus Humano 1 / Dependovirus / Vetores Genéticos Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Revista: J Virol Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Receptoras Sensoriais / Transdução Genética / Herpesvirus Humano 1 / Dependovirus / Vetores Genéticos Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Revista: J Virol Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos