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Insertion of HIV-1 genes into Ad4 Delta E3 vector abrogates increased pathogenesis in cotton rats due to E3 deletion

  1. Author:
    Patterson, L. J.
    Prince, G. A.
    Richardson, E.
    Alvord, W. G.
    Kalyan, N.
    Robert-Guroff, M.

  2. Author Address

    NCI, Basic Res Labs, 41 Lib Dr MSC 5055, Bldg 41, Room D804, Bethesda, MD 20892 USA. NCI, Basic Res Labs, Bethesda, MD 20892 USA. Virion Syst Inc, Rockville, MD USA. Frederick Canc Res & Dev Ctr, Natl Canc Inst, Data Management Serv, Frederick, MD USA. Robert-Guroff M NCI, Basic Res Labs, 41 Lib Dr MSC 5055, Bldg 41, Room D804, Bethesda, MD 20892 USA.
    1. Year: 2002
  2. Journal: Virology
    1. 292
    2. 1
    3. Pages: 107-113
  4. Type of Article: Article
  1. 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), Ad4AE3, 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 Ad4AE3 caused increased overall pathology, while the two HIV recombinant viruses showed effects comparable to Ad4WT (P < 0.01). Our observation that Ad4DeltaE3HIV recombinants areas safe in cotton rats as Ad4WT encourages their continued development as AIDS vaccines. (C) 2002 Elsevier Science.

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