Investigating the distribution of HIV-1 Tat lengths present in the Drexel Medicine CARES cohort

Abstract Human immunodeficiency virus type 1 (HIV-1) encodes for Tat, a multi-functional regulatory protein involved in transcriptional enhancement and in causing neurotoxicity/central nervous system (CNS) dysfunction. This study examines Sanger sequencing of HIV-1 subtype B Tat from 2006 to 2014 within the Drexel University College of Medicine CNS AIDS Research and Eradication Study (CARES) Cohort to investigate Tat length in patients. The Los Alamos National Laboratory (LANL) database was used as a comparator. Miscoded stop codons were present in the CARES Cohort and LANL and protein variability was highly similar. Tat proteins in CARES and LANL were predominantly 101 residues. There was no observed correlation between Tat length and clinical parameters within the CARES Cohort. Unique Tat lengths found in the CARES Cohort and not in LANL were 31, 36, and 39 residues. When CARES patients were longitudinally examined, sequence lengths of 101 had a low probability of reducing to below 48, and sequences had a high probability of increasing to above 86 residues during their next visit, when below 48 residues in length. This suggests that Tat length is conserved to retain the majority of the proteins function highlighting its importance in viral replication.