Accumulation of defective HIV-1 variants in a patient with slow disease progression

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Abstract

Viral population in a long term non progressor carrying CRF02-AG HIV-1 virus variants with a truncated RT gene and attenuated virus replication was analyzed. The proportion of mutant and wild-type RT sequences was determined by clonal analysis of HIV-1 DNA and RNA from blood samples and peripheral blood mononuclear cell (PBMC) culture supernatants. Recombinant HIV-1 strains were generated by reverse genetics to evaluate the replicative capacity of RT variants in PBMC cultures. HIV-1 RNA and DNA sequences in PBMC cultures showed a mixture of stop codons (RT STOP), recombinant forms, (RT RF), and full length (RT FL) strains. In plasma, proportion of HIV-1 RNA sequences with a truncated RT gene fluctuated over time (0% in 2005, 100% in 2007 and 8.3% in 2010), while in proviral DNA was constant (96.5% to 100%). Reconstituted RT STOP strains were unable to replicate in PBMC. However, RT FL strains could trans-complement the loss of function of RT STOP variants. In vivo selection of stop codons in the RT gene resulted in the accumulation of replication-defective virus strains. Nevertheless, the observed release of defective viral particles in plasma was probably the result of viral protein complementation between replication-competent and replication-incompetent HIV-1 variants. The divergence in the proportion of RT STOP and RT FL variants as well as in the mutation's pattern to antiretroviral drug resistance between HIV- 1 plasma RNA and PBMC proviral DNA, suggested that circulating lymphocytes expressing full-length RT might be negatively selected for by a specific T-cell response, possibly contributing to the slow progression to AIDS observed in this patient.

Original languageEnglish
Pages (from-to)17-22
Number of pages6
JournalCurrent HIV Research
Volume9
Issue number1
DOIs
Publication statusPublished - 2011

Keywords

  • Defective variants
  • HIV-1
  • Pol mutations
  • RT stop codons
  • Slow progressor
  • Viral complementation
  • Viral replication

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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