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Updated: Jan 20, 2026

Evaluation of the Efficacy And Toxicity of RNAs Targeting HIV-1 Production for Use in Gene or Drug Therapy
Published on: September 5, 2016
Insertion of HIV-1 genes into Ad4DeltaE3 vector abrogates increased pathogenesis in cotton rats due to E3 deletion
L Jean Patterson1, Gregory A Prince, Ersell Richardson
1Basic Research Laboratory, National Cancer Institute, Bethesda, Maryland, USA.
Abstract:
Adenovirus type 5 (Ad5) E3 region proteins abrogate Ad pathogenicity in the lungs of cotton rats. Our use of Ad4-HIV E3-deleted (DeltaE3) recombinants as vaccines necessitates further examination of these viruses for enhanced pathogenesis. Equivalent infectious doses of Ad4 wild-type (Ad4WT), Ad4DeltaE3, and two recombinants: Ad4DeltaE3HIVenv and Ad4DeltaE3HIVgag, were inoculated intranasally into cotton rats. Ad4 viruses did not replicate in the lungs, but caused mild pathologic effects, including peribronchiolitis, bronchitis, alveolitis, and interstitial pneumonia. As found previously for Ad5, deletion of Ad4 E3 genes resulted in increased lung pathology. Surprisingly, insertion of HIV genes into this region significantly restored protection attributed to E3 gene products, diminishing overall pathologic effects to Ad4WT levels (P < 0.0001). Similarly, following administration of equivalent particle numbers of the four viruses, only Ad4DeltaE3 caused increased overall pathology, while the two HIV recombinant viruses showed effects comparable to Ad4WT (P < 0.01). Our observation that Ad4DeltaE3HIV recombinants are as safe in cotton rats as Ad4WT encourages their continued development as AIDS vaccines.
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