A role for the tat protein of hiv-1 in suppression of viral...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/11 (2006.01) C07K 14/16 (2006.01) C12N 5/10 (2006.01) C12N 15/49 (2006.01) C12N 15/86 (2006.01) C12Q 1/68 (2006.01) C12Q 1/70 (2006.01)

Patent

CA 2335410

We have examined the role of the human immunodeficiency virus type-1 (H1V-1) Tat protein in the regulation of reverse transcription. We show that a 2 exon- but not a 1- exon-form of Tat markedly suppressed cell-free reverse transcriptase (RT) activity. Conversely, viruses expressing 2-exon-Tat (pNL43 and pNL101) showed rapid replication kinetics and more efficient endogenous RT activity compared with viruses expressing 1-exon Tat (pM1ex). The pM1ex virions as well as pM1ex-infected cells also contained higher levels of viral DNA than did either the pNL43 or pNL101 viruses, indicating that reverse transcription might have continued during later stages of viral replication in the absence of the second Tat exon. Moreover, degradation of viral genomic RNA was more apparent in the pM1ex virions. Accordingly, we propose that 2 exon Tat may help augment viral infectivity by suppressing the reverse transcription reaction during late stages of viral synthesis and by preventing the synthesis of potentially deleterious viral DNA products.~

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