High Rates of Human Immunodeficiency Virus Type 1 Mutational Profiles by Single-Genome Amplification after 48-Hour Propagation in Peripheral Blood Mononuclear Cells at Different Levels of Cell Activation

High Rates of Human Immunodeficiency Virus Type 1 Mutational Profiles by Single-Genome Amplification after 48-Hour Propagation in Peripheral Blood Mononuclear Cells at Different Levels of Cell Activation

Author Russo, Cristiano Teodoro Google Scholar
Alkmim, Wagner Autor UNIFESP Google Scholar
Munerato, Patricia Autor UNIFESP Google Scholar
Zukurov, Jean Autor UNIFESP Google Scholar
Maricato, Juliana Terzi Autor UNIFESP Google Scholar
Sucupira, M. Cecilia Autor UNIFESP Google Scholar
Diaz, Ricardo S. Autor UNIFESP Google Scholar
Janini, Luiz Mario Autor UNIFESP Google Scholar
Institution Pontif Catholic Univ Parana
Universidade Federal de São Paulo (UNIFESP)
Abstract Human immunodeficiency virus type 1 (HIV-1) genetic diversity is one of the most important features of HIV-1 infections and the result of error accumulation during reverse transcription and of high viral turnover. HIV-1 reverse transcription is influenced by factors such as the level of nucleotides and/or the cellular activation state. HIV-1 diversity was investigated after 48 h of viral propagation in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors in three different cell culture conditions: (1) resting PBMCs, (2) simultaneous infection and PBMC activation, and (3) PBMC activation 72 h before infection. Cellular DNA was extracted and proviruses of each culture condition were amplified. Single-genonne PCR clones were obtained and the protease and reverse transcriptase of the pol gene were sequenced. An elevated number of nucleotide substitutions in all three culture conditions were observed. in condition 1, the mutational rate observed ranged from 1.0 x 10(-3) to 2.1 x 10(-2), the genetic diversity was 0.6%, and hypermutation was observed in 7.1% of sequenced clones. in condition 2, the mutational rate ranged from 1.0 x 10(-3) to 1.0 x 10(-2), the genetic diversity was 0.8%, and hypermutation affected 6.7% of clones. in condition 3, the mutational rate ranged from 2.8 x 10(-3) to 1.1 x 10(-2), the genetic diversity was 1%, and 5.9% of clones were hypermutated. Substitutions occurred more frequently in some specific nucleotide stretches, and a common pattern for substitutions in all the different conditions was identified. There was a significant accumulation of mutations during the initial periods of in vitro HIV-1 propagation irrespective of culture conditions. the rapid accumulation of virus diversity might represent a viral strategy when colonizing new hosts. Complementary studies are necessary to allow for a better understanding of the initial periods of infection, which represent a crucial event related to disease progression. (C) 2014 S. Karger AG, Basel
Keywords HIV-1
Pol region
Viral propagation
Peripheral blood
Mononuclear cells
Mutation
Genetic diversity
Language English
Date 2014-01-01
Published in Intervirology. Basel: Karger, v. 57, n. 5, p. 277-288, 2014.
ISSN 0300-5526 (Sherpa/Romeo, impact factor)
Publisher Karger
Extent 277-288
Origin http://dx.doi.org/10.1159/000362415
Access rights Closed access
Type Article
Web of Science ID WOS:000340812800005
URI http://repositorio.unifesp.br/handle/11600/37290

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