Abstract
Functional genes of HIV-1 like the tat express proteins essential for viral survival and propagation. There are variations reported in levels of Tat transactivation among the different subtypes of HIV-1. This study looked at the amino acid differences in the different regions of Tat protein (exon 1) of subtype B and C strains of HIV-1 and tried to observe a molecular basis for protein function. HIV-1 sequences of subtype B (n=30) and C (n=60) strains were downloaded from HIV-1 Los Alamos data base. Among the 60 subtype C strain sequences, 30 each were from India and Africa. A HIV-1 Tat protein (exon 1) sequence, the consensus B and C sequence was obtained from the 'sequence search interface' in the Los Alamos HIV-1 sequence data. The sequences were visualized using Weblogo and the RNA binding regions of the three consensus sequences were also determined using BindN software program. Compared to subtype B, there was a high level of divergence in the auxiliary domain of tat exon 1 (amino acid positions 58- 69). The net charge of the subtype C (Indian) Tat protein (exon 1) auxiliary domain was -1.9 at pH 7 and it had an isoelectric point of 4.1. The net charge of the subtype C (African) auxiliary domain was -2.9 at pH 7 and it had an isoelectric point of 3.7 while the net charge of same region in subtype B was -0.9 at pH 7 with an isoelectric point of 4.9. The ratio of the hydrophilic residues to the total number of residues was 60% in the in both the Indian and African subtype C in the auxiliary domain while this was 50% in subtype B. The consensus subtype B sequence was found to have 36 RNA binding sites while subtype C (India) had 33 and subtype C (Africa) had 32 RNA binding sites. The HIV-1 Tat-TAR interaction is a potential target for inhibitors and being considered for its potential use in HIV-1 vaccines. Development of such inhibitor/vaccines would have to take into consideration the variation in amino acid sequence analyzed in this study as this could determine epitope presentation on MHC class I antigen for afferent immune response.
Highlights
The M group of human immunodeficiency virus-1 (HIV-1) is divided into nine non-recombinant subtypes (A-D, F-H, J, K) [1]
In addition to structural genes HIV-1 has functional genes which express proteins essential for viral survival and propagation [3]. One such functional gene tat mediates an important role in transcription of the HIV-1 LTR [4]
We have used Tat HIV-1 sequences of subtype B and subtype C strains obtained from GenBank and attempted to observe for amino acid differences in the different regions of Tat protein of subtype B and C strains to find a molecular basis for differences in protein function
Summary
The M group of human immunodeficiency virus-1 (HIV-1) is divided into nine non-recombinant subtypes (A-D, F-H, J, K) [1]. Mutational analysis studies have shown that Tat protein can be functionally organized into different domains [7]. We have used Tat (exon1) HIV-1 sequences of subtype B and subtype C strains obtained from GenBank and attempted to observe for amino acid differences in the different regions of Tat protein (exon 1) of subtype B and C strains to find a molecular basis for differences in protein function. The accession numbers of the CXCR4 and CCR5 utilizing strain were obtained from the dataset used to construct classifiers for Wetcat, which allows determination of HIV-1 co-receptor usage (http://genomiac2.ucsd.edu:8080/wetcat/ v3.html). A HIV-1 Tat protein (exon 1) sequence was obtained from the ‘sequence search interface’ in the Los Alamos HIV-1 sequence data http://www.hiv.lanl.gov/components/sequence/HIV/search/search.html. The alignment of the nucleotide and amino acid sequences obtained was done using clustalW (http://www.ebi.ac.uk/Tools/ clustalw/). The evolutionary distances were computed using the Poisson correction method
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