Multiple immediate-early gene-deficient herpes simplex virus vectors allowing efficient gene delivery to neurons in culture and widespread gene del… – PubMed

Multiple immediate-early gene-deficient herpes simplex virus vectors allowing efficient gene delivery to neurons in culture and widespread gene del... - PubMed

Autoinoculation and dissemination (or Kaposi’s varicelliform eruption (KVE) or eczema herpeticum) of herpetic lesions are two forms of viral spread, and it is essential to differentiate the two. Ultracentrifugation at 20,000 to 25,000 rpm (28,000 to 45,000 X g) for 1.5 to 2.3 h was utilized with good preservation of cultures. Three to five weeks after oral inoculation of SCID mice with HSV-1 strain in1814, a persistent viral infection of the gastrointestinal tract was established in most of the mice. To investigate this, we directly infected ganglia of mice with HSV and evaluated latency. Cell-free enveloped HSV-1 virions were observed, indicating productive infection. These results indicate that (1) a unique and interesting pattern of bilateral ocular disease occurs after uniocular anterior chamber injection of HSV-1 in mice; (2) the distribution of the destructive lesions differs between the injected eye and its uninjected counterpart; and (3) local factors, perhaps produced within the eye itself, modify the progression of the virus-induced reaction within the globe. A robust signal for the TK gene and its encoding protein was detected selectively within the regions that exhibited expression of the immune molecules.
Multiple immediate-early gene-deficient herpes simplex virus vectors allowing efficient gene delivery to neurons in culture and widespread gene del... - PubMed

At 5 x 10(-1) mg/ml the number of plaques was reduced about 67%. The remaining ulcers, although devoid of viral proteins, were found adjacent to virus-infected ganglia. A. Antimicrob. Abundant cellular GFP expression has been shown in vitro 24 hours after infection by the d106 virus.26 GFP expression was determined 48 hours after stereotactic CED or manual injection of d106. Second, it is shown that the nucleoside transport inhibitor also blocks wild-type HSV reactivation from latency. Unlike less-disabled viruses, these vectors allow highly effective gene delivery both to neurons in culture and to the central nervous system in vivo.

Gene delivery in vivo is further enhanced by the retrograde transport capabilities of HSV. Here the vector is efficiently transported from the site of inoculation to connected sites within the nervous system. This is demonstrated by gene delivery to both the striatum and substantia nigra following striatal inoculation; to the spinal cord, spinal ganglia, and brainstem following injection into the spinal cord; and to retinal ganglion neurons following injection into the superior colliculus and thalamus.

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