HIV-1 genome is often defective in PBMCs and rectal tissues after long-term HAART as a result of APOBEC3 editing and correlates with the size of reservoirs.
J Antimicrob Chemother
; 67(10): 2323-6, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-22687892
ABSTRACT
OBJECTIVES:
Precise characterization of viruses present in reservoirs in long-term pretreated patients will be a major issue to consider in the context of viral eradication. We assessed the frequency of defective viruses present in cellular reservoirs.METHODS:
Peripheral blood mononuclear cells (PBMCs) and rectal biopsy samples were compared between five patients on successful long-term highly active antiretroviral therapy (HAART) (>7 years without blips) and five untreated patients. Molecular cloning and sequencing of the reverse transcriptase region were used to detect the presence of and quantify in-frame stop codons in HIV quasi-species. The relationship between the size of the reservoir and the frequency of defective genomes was assessed.RESULTS:
Defective genomes were systematically detected in all patients on long-term HAART in both compartments (PBMCs and rectal tissues), with a higher level of defective genomes per sample compared with PBMCs of untreated patients. A high level of defective genomes was correlated with a small size of HIV proviral DNA. Regarding the nucleotide context, guanine (G) to adenine (A) substitution at tryptophan positions was responsible for the appearance of 89% of all in-frame stop codons in the context of G-to-A hypermutation, likely reflecting APOBEC3 footprints on the viral genome.CONCLUSIONS:
We propose a scenario whereby defective genomes accumulate during HAART treatment, eventually reaching a viral extinction threshold. In the context of viral eradication, measurement of the relative amounts of defective and non-defective viruses (by molecular cloning and ultradeep sequencing) should be used as a new criterion for eradicating HIV.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucócitos Mononucleares
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Infecções por HIV
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HIV-1
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Terapia Antirretroviral de Alta Atividade
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Vírus Defeituosos
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Citosina Desaminase
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Mucosa Intestinal
Limite:
Adolescent
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
J Antimicrob Chemother
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
França