title: Comparative genetic variability in HIV-1 subtype C nef gene in early age groups of infants.
abstract: Targeting properties of vertically transmitted viruses in early infancy is important to understand disease progression. To investigate genotypic characteristics of transmitted viruses, blood samples were obtained from infants aged 6 weeks-18 months, categorized in two age groups, acute (<6 months) and early (>6-18 months). Nef having an important role in pathogenesis was selected to explore the viral characteristics. A total of 57 PCR positive samples, amplified by nef gene were sequenced. Analysis showed that 50 sequences belonged to subtype C. In one sequence of acute age group, a long insertion of 10 residues (AAERMRRAEP) in variable region and a 13 residues deletion (ATNNADCAWLEAQ) around proteolytic cleavage region of gene in another sequence was observed. Insertions were also observed in sequences of early age group, however, they ranged from two to eight residues only. In one sequence of early age group, 3/4 arginines at positions 19, 21, 22 of arginine cluster were mutated to glutamine, alanine, and glutamine, respectively. Entropy analysis of two age groups revealed presence of several residues with statistically significant differences in their variability. Among these, 15 (R18,R23,R24; A66,L68,Q71; E74,E77,E78; V87,M92; R119, P144, E167, and C176) belonged to functional motifs, out of which, 12 were in acute age group, suggesting that variability was greater in this group. Prediction of HLA binding peptide motif revealed that epitope LTFGWCFKL was present in >80% study sequences. This epitope was also present in maximum number of HLA types circulating in India and vaccine candidate sequences, suggesting that it may be helpful in designing an epitope-based vaccine.
authors.affiliation: Molecular Virology Laboratory, Department of Biotechnology, Jamia Millia Islamia, New Delhi, India.|National Centre for Disease Control, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India, Delhi, India.
authors.forename: Uma
authors.initials: U
authors.lastname: Sharma
authors.affiliation: Molecular Virology Laboratory, Department of Biotechnology, Jamia Millia Islamia, New Delhi, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Gupta
authors.affiliation: National Centre for Disease Control, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India, Delhi, India.
authors.forename: Megha
authors.initials: M
authors.lastname: Singhal
authors.affiliation: National Centre for Disease Control, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India, Delhi, India.
authors.forename: Supriya
authors.initials: S
authors.lastname: Singh
authors.affiliation: National Centre for Disease Control, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India, Delhi, India.
authors.forename: Sunil
authors.initials: S
authors.lastname: Gupta
authors.affiliation: National Centre for Disease Control, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India, Delhi, India.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Venkatesh
authors.affiliation: National Centre for Disease Control, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India, Delhi, India.
authors.forename: Arvind
authors.initials: A
authors.lastname: Rai
authors.affiliation: Molecular Virology Laboratory, Department of Biotechnology, Jamia Millia Islamia, New Delhi, India.
authors.forename: Mohammad
authors.identifier: 0000-0003-3876-8181
authors.initials: M
authors.lastname: Husain
mesh_terms: D001769:Blood / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007194:India; D007223:Infant; D009154:Mutation; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000145:classification / Q000235:genetics*
chemical_list: D018984:Epitopes, T-Lymphocyte; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1
keywords: HIV-1; MTCT; genetic variability; infants; motif; nef