title: The Evolving Profile of the Signature Amino Acid Residues in HIV-1 Subtype C Tat.
abstract: Using several HIV-1 tat exon 1 amino acid sequences available from public databases and additional sequences derived from a southern Indian clinical cohort, we compared the profile of the signature amino acid residues (SAR) between two different time periods, 1986-2004 and 2005-2014. The analysis identified eight positions as signature residues in subtype C Tat and demonstrated a changing pattern at four of these positions between the two periods. At three locations (histidine 29, serine 57, and proline 60), there appears to be a nonuniform negative selection against the SAR. The negative selection appears to be severe, especially against histidine 29 (p < .0001) and moderate against proline 60 (p < .0001). The negative selection against serine 57 is statistically insignificant and appears to have begun recently. At position 63, the frequency of signature residue glutamic acid increased over the past decade, although the difference was not significant. Importantly, at the three locations where the negative selection is in progress, the substitute amino acids are the generic residues present in most of the other HIV-1 subtypes. Our data demonstrate that viral evolution can subject specific amino acid residues to subtle and progressive selection pressures without affecting the prevalence of other amino acid residues.
authors.affiliation: 1 Molecular Biology and Genetics Unit, HIV-AIDS Laboratory, Jawaharlal Nehru Centre for Advanced Scientific Research , Bengaluru, India .
authors.forename: Shambhu Prasad G
authors.initials: SP
authors.lastname: Aralaguppe
authors.affiliation: 1 Molecular Biology and Genetics Unit, HIV-AIDS Laboratory, Jawaharlal Nehru Centre for Advanced Scientific Research , Bengaluru, India .
authors.forename: Shilpee
authors.initials: S
authors.lastname: Sharma
authors.affiliation: 1 Molecular Biology and Genetics Unit, HIV-AIDS Laboratory, Jawaharlal Nehru Centre for Advanced Scientific Research , Bengaluru, India .
authors.forename: Malini
authors.initials: M
authors.lastname: Menon
authors.affiliation: 2 Department of Microbiology and Immunology, Albert Einstein College of Medicine , Bronx, New York, New York.
authors.forename: Vinayaka R
authors.initials: VR
authors.lastname: Prasad
authors.affiliation: 3 YRG Centre for AIDS Research and Education , Chennai, India .
authors.forename: Shanmugam
authors.initials: S
authors.lastname: Saravanan
authors.affiliation: 3 YRG Centre for AIDS Research and Education , Chennai, India .
authors.forename: Kailapuri G
authors.initials: KG
authors.lastname: Murugavel
authors.affiliation: 3 YRG Centre for AIDS Research and Education , Chennai, India .
authors.forename: Suniti
authors.initials: S
authors.lastname: Solomon
authors.affiliation: 1 Molecular Biology and Genetics Unit, HIV-AIDS Laboratory, Jawaharlal Nehru Centre for Advanced Scientific Research , Bengaluru, India .
authors.forename: Udaykumar
authors.initials: U
authors.lastname: Ranga
mesh_terms: D000293:Adolescent; D000328:Adult; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001483:Base Sequence; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D055815:Young Adult; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
chemical_list: D054322:tat Gene Products, Human Immunodeficiency Virus