The PTAP sequence duplication in HIV-1 subtype C Gag p6 in drug-naive subjects of India and South Africa

Simple item page
dc.contributor.authorSharma, Shilpee
dc.contributor.authorAralaguppe, Shambhu G
dc.contributor.authorAbrahams, Melissa-Rose
dc.contributor.authorWilliamson, Carolyn
dc.contributor.authorGray, Clive
dc.contributor.authorBalakrishnan, Pachamuthu
dc.contributor.authorSaravanan, Shanmugam
dc.contributor.authorMurugavel, Kailapuri G
dc.contributor.authorSolomon, Suniti
dc.contributor.authorRanga, Udaykumar
dc.date.accessioned2021-10-08T06:20:31Z
dc.date.available2021-10-08T06:20:31Z
dc.date.issued2017
dc.description.abstractAbstract Background 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. Methods 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. Results 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. Conclusion 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.
dc.identifier.apacitationSharma, S., Aralaguppe, S. G., Abrahams, M., Williamson, C., Gray, C., Balakrishnan, P., ... Ranga, U. (2017). The PTAP sequence duplication in HIV-1 subtype C Gag p6 in drug-naive subjects of India and South Africa. <i>BMC Infectious Diseases</i>, 17(1), 174 - 177. http://hdl.handle.net/11427/34297en_ZA
dc.identifier.chicagocitationSharma, Shilpee, Shambhu G Aralaguppe, Melissa-Rose Abrahams, Carolyn Williamson, Clive Gray, Pachamuthu Balakrishnan, Shanmugam Saravanan, Kailapuri G Murugavel, Suniti Solomon, and Udaykumar Ranga "The PTAP sequence duplication in HIV-1 subtype C Gag p6 in drug-naive subjects of India and South Africa." <i>BMC Infectious Diseases</i> 17, 1. (2017): 174 - 177. http://hdl.handle.net/11427/34297en_ZA
dc.identifier.citationSharma, S., Aralaguppe, S.G., Abrahams, M., Williamson, C., Gray, C., Balakrishnan, P., Saravanan, S. & Murugavel, K.G. et al. 2017. The PTAP sequence duplication in HIV-1 subtype C Gag p6 in drug-naive subjects of India and South Africa. <i>BMC Infectious Diseases.</i> 17(1):174 - 177. http://hdl.handle.net/11427/34297en_ZA
dc.identifier.issn1471-2334
dc.identifier.ris TY - Journal Article AU - Sharma, Shilpee AU - Aralaguppe, Shambhu G AU - Abrahams, Melissa-Rose AU - Williamson, Carolyn AU - Gray, Clive AU - Balakrishnan, Pachamuthu AU - Saravanan, Shanmugam AU - Murugavel, Kailapuri G AU - Solomon, Suniti AU - Ranga, Udaykumar AB - Abstract Background 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. Methods 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. Results 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. Conclusion 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. DA - 2017 DB - OpenUCT DP - University of Cape Town IS - 1 J1 - BMC Infectious Diseases LK - https://open.uct.ac.za PY - 2017 SM - 1471-2334 T1 - The PTAP sequence duplication in HIV-1 subtype C Gag p6 in drug-naive subjects of India and South Africa TI - The PTAP sequence duplication in HIV-1 subtype C Gag p6 in drug-naive subjects of India and South Africa UR - http://hdl.handle.net/11427/34297 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/34297
dc.identifier.vancouvercitationSharma S, Aralaguppe SG, Abrahams M, Williamson C, Gray C, Balakrishnan P, et al. The PTAP sequence duplication in HIV-1 subtype C Gag p6 in drug-naive subjects of India and South Africa. BMC Infectious Diseases. 2017;17(1):174 - 177. http://hdl.handle.net/11427/34297.en_ZA
dc.language.isoeng
dc.publisher.departmentDepartment of Pathology
dc.publisher.facultyFaculty of Health Sciences
dc.sourceBMC Infectious Diseases
dc.source.journalissue1
dc.source.journalvolume17
dc.source.pagination174 - 177
dc.source.urihttps://dx.doi.org/10.1186/s12879-017-2184-4
dc.subject.otherGag
dc.subject.otherHIV evolution
dc.subject.otherHIV-1
dc.subject.otherPTAP duplication
dc.subject.otherSubtype C
dc.subject.otherp6
dc.subject.otherAdult
dc.subject.otherFemale
dc.subject.otherFollow-Up Studies
dc.subject.otherHIV Infections
dc.subject.otherHIV-1
dc.subject.otherHumans
dc.subject.otherIndia
dc.subject.otherLongitudinal Studies
dc.subject.otherMale
dc.subject.otherMiddle Aged
dc.subject.otherProspective Studies
dc.subject.otherRNA, Viral
dc.subject.otherSouth Africa
dc.subject.otherYoung Adult
dc.subject.othergag Gene Products, Human Immunodeficiency Virus
dc.subject.otherRNA, Viral
dc.subject.othergag Gene Products, Human Immunodeficiency Virus
dc.titleThe PTAP sequence duplication in HIV-1 subtype C Gag p6 in drug-naive subjects of India and South Africa
dc.typeJournal Article
uct.type.publicationResearch
uct.type.resourceJournal Article
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
SharmaShilpee_PTAP_sequence_d_2017.pdf
Size:
1.66 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Journal Articles