title: The PTAP sequence duplication in HIV-1 subtype C Gag p6 in drug-naive subjects of India and South Africa.
abstract: HIV-1 subtype C demonstrates several biological properties distinct from other viral subtypes. One such variation is the duplication of PTAP motif in p6 Gag. PTAP motif is a key player in viral budding. Here, we studied the prevalence of PTAP motif duplication in subtype C viral strains in a longitudinal study.
  
  
  
  In a prospective follow-up study, 65 HIV-1 seropositive drug-naive subjects were monitored in two different clinical cohorts of India for 2 years with repeated sampling at 6-month intervals. The viral RNA was extracted from plasma, the gag segment was amplified and sequenced. From a subset of viral isolates the sequences of pol, env and LTR were sequenced. Using HIV-1 gag amino acid sequences available from public databases and additional sequences derived from the Indian and South-African cohorts, we examined the nature of PTAP motif duplication in subtype C.
  
  
  
  In 16% (8 of 50) of the primary viral strains of India, we identified a sequence duplication of the PTAP motif in Gag p6. The length of the sequence duplication varied from 6 to 14 amino acids in the viral isolates but remained fixed within a subject over a period of 24-36 month follow-up. In the duplicated motif, the core PTAP motif was invariable, but the flanking residues were highly variable. In an acute phase clinical cohort of South Africa, in a subset of 75 subjects, we found the presence of the PTAP duplication at a frequency of 29.3%. An analysis of the gag sequences from the extant databases showed that unlike other subtypes of HIV-1, subtype C has a natural propensity to generate the PTAP motif duplication at a significantly higher frequency and of greater length. Additionally, the global prevalence of PTAP duplication in subtype C appears to be increasing progressively over the past 30 years.
  
  
  
  We showed that in subtype C, the duplication of the PTAP motif in p6 Gag involves sequence stretches of greater length, and at a much higher frequency as compared to other HIV-1 subtypes. Given that subtype C naturally lacks the Alix binding motif, the acquisition of an additional PTAP motif may confer replication advantage on this HIV-1 subtype. Further investigation is warranted to examine the significance of PTAP motif duplication on the replicative fitness of HIV-1.
authors.affiliation: Jawaharlal Nehru Centre for Advanced Scientific Research, HIV-AIDS Laboratory, Jakkur (PO), Bangalore, 560 064, India.
authors.forename: Shilpee
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Jawaharlal Nehru Centre for Advanced Scientific Research, HIV-AIDS Laboratory, Jakkur (PO), Bangalore, 560 064, India.
authors.forename: Shambhu G
authors.initials: SG
authors.lastname: Aralaguppe
authors.affiliation: Division of Medical Virology and Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Department of Pathology, University of Cape Town, and National Health Laboratory Service, Cape Town, South Africa.
authors.forename: Melissa-Rose
authors.initials: MR
authors.lastname: Abrahams
authors.affiliation: Division of Medical Virology and Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Department of Pathology, University of Cape Town, and National Health Laboratory Service, Cape Town, South Africa.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Williamson
authors.affiliation: Division of Medical Virology and Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Department of Pathology, University of Cape Town, and National Health Laboratory Service, Cape Town, South Africa.
authors.forename: Clive
authors.initials: C
authors.lastname: Gray
authors.affiliation: YRG Centre for AIDS Research and Education, Chennai, India.
authors.forename: Pachamuthu
authors.initials: P
authors.lastname: Balakrishnan
authors.affiliation: YRG Centre for AIDS Research and Education, Chennai, India.
authors.forename: Shanmugam
authors.initials: S
authors.lastname: Saravanan
authors.affiliation: YRG Centre for AIDS Research and Education, Chennai, India.
authors.forename: Kailapuri G
authors.initials: KG
authors.lastname: Murugavel
authors.affiliation: YRG Centre for AIDS Research and Education, Chennai, India.
authors.forename: Suniti
authors.initials: S
authors.lastname: Solomon
authors.affiliation: Jawaharlal Nehru Centre for Advanced Scientific Research, HIV-AIDS Laboratory, Jakkur (PO), Bangalore, 560 064, India. udaykumar@jncasr.ac.in.
authors.forename: Udaykumar
authors.initials: U
authors.lastname: Ranga
mesh_terms: D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis; D013019:South Africa / Q000453:epidemiology; D055815:Young Adult; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
chemical_list: D012367:RNA, Viral; D054301:gag Gene Products, Human Immunodeficiency Virus
keywords: Gag; HIV evolution; HIV-1; PTAP duplication; Subtype C; p6