An in vitro Model to Mimic Selection of Replication-Competent HIV-1 Intersubtype Recombination in Dual or Superinfected Patients

Bernard S Bagaya, Meijuan Tian, Gabrielle C Nickel, José F Vega, Yuejin Li, Ping He, Katja Klein, Jamie F S Mann, Wei Jiang, Eric J Arts, Yong Gao

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

The low frequency of HIV-1 recombinants within entire viral populations in both individual patients and culture-based infection models impedes investigation of the underlying factors contributing to either the occurrence of recombinants or the survival of recombinants once they are formed. So far, most of the related studies have no consideration of recombinants' functionality. Here, we established a functional recombinant production (FRP) system to produce pure and functional HIV-1 intersubtype Env recombinants and utilized 454 pyrosequencing to investigate the distribution of over 4000 functional and non-functional recombination breakpoints from either the FRP system or dual infection cultures. The results revealed that most of the breakpoints converged in gp41 (62%) and C1 (25.3%) domains of gp120, which has strong correlation with the similarity between the two recombining sequences. Yet, the breakpoints also appeared in C2 (5.2%) and C5 (4.6%) domains not correlated with the recombining sequence similarity. Interestingly, none of the intersubtype gp120 recombinants recombined between C1 and gp41 regions either from the FRP system or from the dual infection culture, and very few from the HIV epidemic were functional. The present study suggests that the selection of functional Env recombinants is one of the reasons for the predominance of C1 and gp41 Env recombinants in the HIV epidemic, and it provides an in vitro model to mimic the selection of replication-competent HIV-1 intersubtype recombination in dual or superinfected patients.

Original languageEnglish
Pages (from-to)2246-2264
Number of pages19
JournalJournal of Molecular Biology
Volume429
Issue number14
DOIs
Publication statusPublished - 7 Jul 2017

Bibliographical note

Copyright © 2017 Elsevier Ltd. All rights reserved.

Keywords

  • Cell Line
  • Genotype
  • HIV-1/genetics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Recombination, Genetic
  • Selection, Genetic
  • Virus Cultivation/methods
  • env Gene Products, Human Immunodeficiency Virus/genetics

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