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Contribution of APOBEC3G/F activity to the development of low-abundance drug-resistant human immunodeficiency virus type 1 variants.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Noguera-Julian M, Cozzi-Lepri A, Di Giallonardo F, Schuurman R, Däumer M, Aitken S, Ceccherini-Silberstein F, D'Arminio Monforte A, Geretti A M, Booth C L, Kaiser R, Michalik C, Jansen K, Masquelier B, Bellecave P, Kouyos R D, Castro E, Furrer H, Schultze A, Günthard H F, Brun-Vezinet F, Metzner K J, Paredes R, CHAIN Minority HIV-1 Variants Working group,
Project Swiss HIV Cohort Study (SHCS)
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Original article (peer-reviewed)

Journal Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
Volume (Issue) 22(2)
Page(s) 191 - 200
Title of proceedings Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
DOI 10.1016/j.cmi.2015.10.004

Open Access

Type of Open Access Publisher (Gold Open Access)


Plasma drug-resistant minority human immunodeficiency virus type 1 variants (DRMVs) increase the risk of virological failure to first-line non-nucleoside reverse transcriptase inhibitor antiretroviral therapy (ART). The origin of DRMVs in ART-naive patients, however, remains unclear. In a large pan-European case-control study investigating the clinical relevance of pre-existing DRMVs using 454 pyrosequencing, the six most prevalent plasma DRMVs detected corresponded to G-to-A nucleotide mutations (V90I, V106I, V108I, E138K, M184I and M230I). Here, we evaluated if such DRMVs could have emerged from apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3G/F (APOBEC3G/F) activity. Out of 236 ART-naive subjects evaluated, APOBEC3G/F hypermutation signatures were detected in plasma viruses of 14 (5.9%) individuals. Samples with minority E138K, M184I, and M230I mutations, but not those with V90I, V106I or V108I, were significantly associated with APOBEC3G/F activity (Fisher's P < 0.005), defined as the presence of > 0.5% of sample sequences with an APOBEC3G/F signature. Mutations E138K, M184I and M230I co-occurred in the same sequence as APOBEC3G/F signatures in 3/9 (33%), 5/11 (45%) and 4/8 (50%) of samples, respectively; such linkage was not found for V90I, V106I or V108I. In-frame STOP codons were observed in 1.5% of all clonal sequences; 14.8% of them co-occurred with APOBEC3G/F signatures. APOBEC3G/F-associated E138K, M184I and M230I appeared within clonal sequences containing in-frame STOP codons in 2/3 (66%), 5/5 (100%) and 4/4 (100%) of the samples. In a re-analysis of the parent case control study, the presence of APOBEC3G/F signatures was not associated with virological failure. In conclusion, the contribution of APOBEC3G/F editing to the development of DRMVs is very limited and does not affect the efficacy of non-nucleoside reverse transcriptase inhibitor ART.