RT Journal Article SR Electronic(1) A1 Berkhout, Ben A1 Klaver, BepYR 1995 T1 Revertants and pseudo-revertants of human immunodeficiency virus type 1 viruses mutated in the long terminal repeat promoter region JF Journal of General Virology, VO 76 IS 4 SP 845 OP 853 DO https://doi.org/10.1099/0022-1317-76-4-845 PB Microbiology Society, SN 1465-2099, AB The TAR domain is an RNA secondary structure element within the leader transcript of the human immunodeficiency virus type 1 (HIV-1) virus. TAR RNA forms the binding site for the viral trans-activator protein Tat and cellular co-factors that are involved in induction of the LTR transcriptional promoter. Here, we report that mutations in the single-stranded bulge- and loop-domains of TAR RNA impair the ability of the virus to replicate in T cell lines. Revertant viruses were isolated upon prolonged culturing and analysed through sequencing. The reversion data confirm the importance of both bulge and loop as sequence-specific recognition motifs. We also analysed the replication phenotype of a mutant HIV-1 virus with a substitution in the -19/-3 promoter region. This mutant displayed delayed infection kinetics compared to the wild-type virus, and revertants with increased replication potential could be isolated. Interestingly, all revertants had acquired an additional mutation at position -2. Primer extension analyses revealed that an upstream shift in transcription start site usage was induced by the -19/-3 substitution. This effect was compensated for by the nucleotide substitution near the RNA start site., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/0022-1317-76-4-845