title: A naturally occurring substitution in human immunodeficiency virus Tat increases expression of the viral genome.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 01701, USA.
authors.forename: Syed M
authors.initials: SM
authors.lastname: Reza
authors.forename: Lin-Ming
authors.initials: LM
authors.lastname: Shen
authors.forename: Rupa
authors.initials: R
authors.lastname: Mukhopadhyay
authors.forename: Mihaela
authors.initials: M
authors.lastname: Rosetti
authors.forename: Tsafi
authors.initials: T
authors.lastname: Pe'ery
authors.forename: Michael B
authors.initials: MB
authors.lastname: Mathews
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001216:Asparagine / Q000737:chemistry; D015696:Gene Products, tat / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014644:Genetic Variation; D016679:Genome, Viral; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear; D008969:Molecular Sequence Data; D042925:Positive Transcriptional Elongation Factor B; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus; D001216:Asparagine; D042925:Positive Transcriptional Elongation Factor B; D017346:Protein Serine-Threonine Kinases