  
Tat protein augments HIV-1 infectivity by suppressing late reverse transcription
Last Updated: 2001-04-09 13:00:43 EDT (Reuters Health)
By Will Boggs, MD
WESTPORT, CT (Reuters Health) - The Tat protein produced by HIV-1 supports viral infectivity by suppressing reverse transcription during the late stages of viral synthesis, according to a report in the March Journal of Virology.
Tat protein is essential for HIV-1 transcription, the authors explain, but its method of regulating viral reverse transcription has not been delineated.
Dr. Mark A. Wainberg and colleagues from McGill University AIDS Centre in Montreal, Quebec, Canada used recombinant Tat proteins containing one or both exons found in wild-type Tat protein to study the role of Tat in reconstituted cell-free reverse transcriptase (RT) reactions.
Two-exon-Tat protein dose dependently suppressed reverse transcription, the authors report, whereas one-exon-Tat protein only slightly suppressed RT reactions even at the highest doses.
Virus particles that encoded only one-exon-Tat possessed replication kinetics substantially delayed in comparison with those of two-exon-Tat-containing viruses, the results indicate.
One-exon-Tat virions also contained higher levels of viral DNA than did two-exon-Tat virions, the researchers found, "indicating that reverse transcription might have continued during later stages of viral replication in the absence of the second Tat exon." Moreover, genomic RNA produced in one-exon-Tat-containing viruses appeared to be significantly more unstable than that produced in two-exon-Tat-containing viruses, the investigators observe.
"Accordingly," the authors conclude, "we propose that the two-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."
The inhibition of reverse transcription at the post-integration stage "ensures, in part, the successful encapsidation of intact viral genome RNA into newly formed virus particles," co-author Dr. Chen Liang told Reuters Health.
Dr. Liang added: "If we can unravel the mechanism whereby Tat protein inhibits reverse transcription in cells, specific compounds will be designed to antagonize this Tat activity and, thereby, compromise HIV replication. Also, efforts are being taken in our lab to locate the effective peptide in Tat sequence that can efficiently inhibit reverse transcription. When such a short peptide is defined, its clinical implications will be tested."
J Virol 2001;75:2675-2683.
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