Abstract:
:Replication-defective human adenovirus (Ad) group C transducing vectors, most of which have the E1A, E1B, and E3 genes deleted, are highly inflammatory despite the fact that the parental viruses typically cause subclinical or mild infections. To investigate this paradox, the roles that the E1A, E1B, and E3 genes play in inflammation were tested by using replication-incompetent viruses carrying a deletion of the preterminal protein gene. The viruses were injected into BALB/c mouse ears, and edema was monitored as a sensitive surrogate marker of inflammation. A virus deleted for the E1A 289R (transcription activating) protein was noninflammatory, and inhibited edema induced by empty virus particles. The E1A 243R and E1B 55-kDa (p53 binding) proteins play the most important roles in inhibition of inflammation by the noninflammatory virus. The E1B 19-kDa antiapoptotic protein inhibited edema when both the E1A 243R and E1B 55-kDa proteins were expressed but strongly induced edema when only one was expressed. E3 proteins had their greatest effect on the inhibition of edema induced by the E1A 289R protein. The results support a model in which inflammation is countered through a mechanism that involves complex genetic interactions between Ad early region proteins and offer promise for the design and construction of noninflammatory Ad gene therapy vectors that are relatively easy to grow and purify.
journal_name
Proc Natl Acad Sci U S Aauthors
Schaack J,Bennett ML,Colbert JD,Torres AV,Clayton GH,Ornelles D,Moorhead Jdoi
10.1073/pnas.0303709101keywords:
subject
Has Abstractpub_date
2004-03-02 00:00:00pages
3124-9issue
9eissn
0027-8424issn
1091-6490pii
0303709101journal_volume
101pub_type
杂志文章abstract::We have earlier reported conditions that support the axenic development in vitro of a complete asexual erythrocytic cycle of Plasmodium falciparum. Up to 30% of merozoites showed initial differentiation into trophic forms (rings) viable at 14 hr. However, only approximately 1% of the merozoites would develop further i...
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