Universität zu Köln

Noguera-Julian, M., Cozzi-Lepri, A., Di Giallonardo, F., Schuurman, R., Daumer, M., Aitken, S., Ceccherini-Silberstein, F., Monforte, A. D'Arminio, 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., Guenthard, H. F., Brun-Vezinet, F., Metzner, K. J. and Paredes, R. (2016). Contribution of APOBEC3G/F activity to the development of low-abundance drug-resistant human immunodeficiency virus type I variants. Clin. Microbiol. Infect., 22 (2). S. 191 - 201. OXFORD: ELSEVIER SCI LTD. ISSN 1469-0691

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Abstract

Plasma drug-resistant minority human immunodeficiency virus type I 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, V1061, VI 081, E 138K, MI841 and M2301). 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, M1841, and M2301 mutations, but not those with V901, V1061 or VI 081, 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, M1841 and M2301 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, V1061 or VI081. 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 E I38K, M1841 and M2301 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. Clinical Microbiology and Infection (C) 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Noguera-Julian, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cozzi-Lepri, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Di Giallonardo, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schuurman, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Daumer, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Aitken, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ceccherini-Silberstein, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Monforte, A. D'Arminio UNSPECIFIED UNSPECIFIED UNSPECIFIED Geretti, A. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Booth, C. L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaiser, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Michalik, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jansen, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Masquelier, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bellecave, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kouyos, R. D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Castro, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Furrer, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schultze, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Guenthard, H. F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brun-Vezinet, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Metzner, K. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Paredes, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-286175
DOI:	10.1016/j.cmi.2015.10.004
Journal or Publication Title:	Clin. Microbiol. Infect.
Volume:	22
Number:	2
Page Range:	S. 191 - 201
Date:	2016
Publisher:	ELSEVIER SCI LTD
Place of Publication:	OXFORD
ISSN:	1469-0691
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CYTIDINE DEAMINATION; HIV-1 REPLICATION; DNA; MUTATIONS; PROTEINS; LYMPHOCYTES; MUTAGENESIS; INFECTION; THERAPY; FAILURE Multiple languages Infectious Diseases; Microbiology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28617