Important note: Information in this article was accurate in December 2002. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, December 23, 2002
Michael Greer, Senior Medical Writer
"Efficient replication and gene expression of human immunodeficiency virus-1 (HIV-1) involves specific interaction of the viral protein Tat, with its trans-activation responsive element (TAR), which forms a highly stable stem-loop structure," according to Neerja Kaushik and colleagues at the University of Medicine and Dentistry of New Jersey's Center for the Study of Emerging and Re-Emerging Pathogens in Newark.
Kauskik and coauthors found that a polyamide nucleotide analog (PNA) could disrupt the Tat-TAR interaction and short-circuit the HIV replication process.
The researchers developed four PNAs targeting the loop and bulge region of HIV TAR. Two of these nucleotide analogs (PNATAR-15 and PNATAR-16) complemented the entire region, while the other two (PNATAR-13 and PNATAR-12) lacked several sequences complementing the loop and/or bulge, according to the report.
The 15- and 16-mer PNAs proved able to efficiently prevent Tat from interacting with TAR's loop and bulge, study data showed. PNATAR-16 reduced HIV virion production by almost 99% in infected cell cultures.
Although the shorter PNAs demonstrated strong affinity for TAR RNA, they had a less pronounced impact on viral replication (Inhibition of HIV-1 replication by anti-trans-activation responsive polyamide nucleotide analog. Antiviral Res 2002 Oct;56(1):13-27.
"These results point to PNATAR-16 as a potential anti-HIV agent," Kaushik and colleagues concluded.
The corresponding author for this report is Virendra N. Pandey, Department of Biochemistry and Molecular Biology, Center for the Study of Emerging and Re-Emerging Pathogens, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103 USA. E-mail: pandey@umdnj.edu.
A search at www.NewsRx.net using the search term "AIDS and HIV therapy" yielded 1193 articles in 29 specialized reports.
Key points reported in this study include:
A polyamide nucleotide analog (PNA) disrupts HIV transactivation activity
The 16-mer PNA prevents HIV Tat from interacting with the viral transactivation responsive element (TAR)
This PNA reduced HIV replication by almost 99%
This article was prepared by AIDS Weekly editors from staff and other reports.
Reference
Kaushik N, Basu A, Pandey VN., "Inhibition of HIV-1 replication by anti-trans-activation responsive polyamide nucleotide analog", Antiviral Res 2002 Oct;56(1):13-27.
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