title: Genetic architecture of HIV type 1 Nef and Tat from HLA-B57-typed long-term survivors in an Indian cohort of perinatally HIV-infected children.
abstract: Human immunodeficiency virus type 1 (HIV-1) viral genes nef and tat play an important role in disease progression. In this study we characterized the Nef and Tat proteins from a group of HLA-B57 typed pediatric perinatally infected long-term survivors (LTS) with ≥10 years of infection. We identified 19 therapy-naive LTS after screening 250 children from an Indian pediatric cohort. Nef and tat amplified from plasma virus showed that all the LTS harbored HIV-1 subtype C. The two B57(+) children showed mutations, deletions, and insertions in experimentally defined B57 epitopes in the virus that are likely to be escape mutants. Only GW12 (GPGVRYPLTFGW) and YY9 (YTPGPGIRY) were conserved, while the remaining 90% (18/20) of the epitopes showed some degree of mutations. The most variable epitopes were RR15, SE15, QP15, KF9, HW9, YT9, and GF15. To our knowledge this is the first study from India in which characterization of Nef and Tat from LTS has led to information on genetic alterations in these genes that are associated with slow disease progression, and can provide an important lead in future studies.
authors.affiliation: 1 Hematology Research Unit , Division of Molecular Medicine, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, India .
authors.forename: Ujjwal
authors.initials: U
authors.lastname: Neogi
authors.forename: Riya
authors.initials: R
authors.lastname: Palchaudhuri
authors.forename: Sankhya
authors.initials: S
authors.lastname: Bommana
authors.forename: Anita
authors.initials: A
authors.lastname: Shet
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D015331:Cohort Studies; D017931:DNA Primers; D005260:Female; D015754:Genes, nef; D015756:Genes, tat; D015658:HIV Infections / Q000635:transmission / Q000821:virology*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000145:classification / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D007194:India; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
chemical_list: D017931:DNA Primers; D015235:HLA-B Antigens; C103707:HLA-B57 antigen