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 (RTSTOP), recombinant forms, (RTRF), and full length (RTFL) 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 RTSTOP strains were unable to replicate in PBMC. However, RTFL strains could trans-complement the loss of function of RTSTOP 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 RTSTOP and RTFL variants as well as in the mutations 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.
Keywords: HIV-1, RT stop codons, viral complementation, viral replication, slow progressor, defective variants, pol mutations, heterozygous, carboxytermints, male bisexual, antiretrovial therapy (ART), drug-resistance, prostease, peripheral blood mononuclear cells (PBMC)
Current HIV Research
Title: Accumulation of Defective HIV-1 Variants in a Patient with Slow Disease Progression
Volume: 9 Issue: 1
Author(s): Stefania Paolucci, Roberto Gulminetti, Renato Maserati, Luca Dossena and Fausto Baldanti
Affiliation:
Keywords: HIV-1, RT stop codons, viral complementation, viral replication, slow progressor, defective variants, pol mutations, heterozygous, carboxytermints, male bisexual, antiretrovial therapy (ART), drug-resistance, prostease, peripheral blood mononuclear cells (PBMC)
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 (RTSTOP), recombinant forms, (RTRF), and full length (RTFL) 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 RTSTOP strains were unable to replicate in PBMC. However, RTFL strains could trans-complement the loss of function of RTSTOP 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 RTSTOP and RTFL variants as well as in the mutations 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.
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Cite this article as:
Paolucci Stefania, Gulminetti Roberto, Maserati Renato, Dossena Luca and Baldanti Fausto, Accumulation of Defective HIV-1 Variants in a Patient with Slow Disease Progression, Current HIV Research 2011; 9 (1) . https://dx.doi.org/10.2174/157016211794582641
DOI https://dx.doi.org/10.2174/157016211794582641 |
Print ISSN 1570-162X |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4251 |
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