Comparative genetic variability in HIV-1 subtype C p24 Gene in early age groups of infants

• Published in: Virus genes 2018-10, Vol.54 (5), p.647-661
• Main Authors: Sharma, Uma, Gupta, Sunil, Venkatesh, S., Rai, Arvind, Dhariwal, A. C., Husain, Mohammad
• Format: Article
• Language: English
• Subjects: Age; Age groups; Amino Acid Motifs; Amino acid substitution; Asparagine; Biomedical and Life Sciences; Biomedicine; Disease transmission; Epitopes; Evolution, Molecular; Genes, Viral; Genetic variability; Genetic Variation; Histocompatibility antigen HLA; HIV; HIV Core Protein p24 - chemistry; HIV Core Protein p24 - genetics; HIV Core Protein p24 - metabolism; HIV Infections - virology; HIV-1 - classification; HIV-1 - genetics; HLA Antigens - metabolism; Homology; Human immunodeficiency virus; Humans; Infant; Infants; Insertion; Medical Microbiology; Mutation; Plant Sciences; Polymerase Chain Reaction; Positive selection; Protein structure; Sequence Analysis, Protein; Virology; Viruses
• ISSN: 0920-8569; 1572-994X
• DOI: 10.1007/s11262-018-1588-6

It is important to study the molecular properties of vertically transmitted viruses in early infancy to understand disease progression. P24 having an important role in virus assembly and maturation was selected to explore the genotypic characteristics. Blood samples, obtained from 82 HIV-1 positive infants, were categorized into acute (≤ 6 months) and early (> 6–18 months) age groups. Of the 82 samples, 79 gave amplification results for p24 , which were then sequenced and analysed. Amino acid heterogeneity analysis showed that substitutions were more frequent. Several substitution mutations were present in some of the sequences of both the age groups in the functional motifs of the gene namely Beta hairpin, CyPA binding loop, residues L136 and L190, linker region and major homology region. In the acute age group, an insertion of Asparagine residue (N5NL6) was observed in the β hairpin region in one of the sequences. This insertion was accompanied with analogous substitutions of N5Q, Q7L and G8R. In the early age group, a deletion of two residues; VK 181−182 , was observed at the C-terminal end in one of the sequences. These mutations may impair the structure of the protein leading to defective virus assembly. Protein variation effect analyzer software showed that deleterious mutations were more in the acute than the early age group. Variability analysis revealed that the amino acid heterogeneity was comparatively higher in the acute than the early age group. Variability in the virus was decreasing with the increasing age of the infants indicating that the virus is gradually evolving under positive selection pressure. HLA class 1 binding peptide analysis showed that the epitopes TPQDLNTML and RMYSPVSIL may be helpful in designing epitope based vaccine.