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Journal of Virology, August 2003, p. 8602-8606, Vol. 77, No. 15
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.15.8602-8606.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

A Naturally Occurring Substitution in Human Immunodeficiency Virus Tat Increases Expression of the Viral Genome

Syed M. Reza,1,2 Lin-Ming Shen,1 Rupa Mukhopadhyay,1 Mihaela Rosetti,1 Tsafi Pe'ery,1,2,3 and Michael B. Mathews1,2*

Departments of Biochemistry and Molecular Biology,1 Medicine, New Jersey Medical School,3 Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 017012

Received 17 March 2003/ Accepted 9 May 2003

A natural amino acid substitution in the human immunodeficiency virus type 1 (HIV-1) transcriptional activator Tat increases its activity and compensates for deleterious mutations elsewhere in the Tat protein. Substitution of asparagine for threonine 23 increases Tat transactivation of the HIV-1 promoter and the binding of Tat to the cellular kinase positive transcription elongation factor b (P-TEFb). Of nine other position 23 mutations tested, only the serine substitution retained wild-type activity. Correspondingly, asparagine is the most frequent amino acid at this position in HIV-1 isolates, followed by threonine and serine. Asparagine is prevalent in Tat proteins of viruses in clades A, C, and D, which are major etiologic agents of AIDS. We suggest that selection for asparagine in position 23 confers an advantage to the virus, since it can compensate for deleterious mutations in Tat. It may also support the replication of otherwise less fit drug-resistant viruses and permit the emergence of virulent strains.


* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, New Jersey Medical School, UMDNJ, 185 South Orange Ave., P.O. Box 1709, Newark, NJ 01701-1709. Phone: (973) 972-4411. Fax: (973) 972-5594. E-mail: mathews{at}umdnj.edu.


Journal of Virology, August 2003, p. 8602-8606, Vol. 77, No. 15
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.15.8602-8606.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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