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In vitro study of the mutation rate of human immunodeficiency virus type 1 (HIV-1) in a single replication round.

Abstract

Human Immunodeficiency Virus types 1 and 2 (HIV-1 and 2) are retroviruses in which genetic diversity is especially high. Such diversity is due to virus properties, and the main aspect contributing to this is the lack of proofreading activity of the enzyme reverse transcriptase (RT). Recombination of different strains of HIV and the high titers of virus produced in the infected host are examples of others elements playing a role in generating the genetic heterogeneity. That genetic diversity enables the virus to i) evade the responses from the human immune system, ii) overcome the effects of current antiretroviral drugs, and iii) impose a major difficulty in developing an effective vaccine or new drugs. The mutation rate was already calculated for HIV-1, but the use of purified reverse transcriptase, short sequences of nucleic acid derived from others organisms, or bacterial phenotypic characteristics based method for mutant virus detection could all induce to a misunderstanding of the phenomenon in this virus species. For these reasons, we propose to re-evaluate the mutation rate of HIV-1 by direct examination of long provirus sequences. We plan to obtain the sequences from peripheral blood mononuclear cells infected in vitro with virus prepared to perform a single replication cycle, to sequence a region of 600 base-pairs long from the env gene, and then calculate the frequency of mutation/ base/ replication cycle. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ZUKUROV, JEAN P.; DO NASCIMENTO-BRITO, SIEBERTH; VOLPINI, ANGELA C.; OLIVEIRA, GUILHERME C.; JANINI, LUIZ MARIO R.; ANTONELI, FERNANDO. Estimation of genetic diversity in viral populations from next generation sequencing data with extremely deep coverage. Algorithms for Molecular Biology, v. 11, . (09/14543-0)
NASCIMENTO-BRITO, SIEBERTH; ZUKUROV, JEAN PAULO; MARICATO, JULIANA T.; VOLPINI, ANGELA C.; SALIM, ANNA CHRISTINA M.; ARAUJO, FLAVIO M. G.; COIMBRA, RONEY S.; OLIVEIRA, GUILHERME C.; ANTONELI, FERNANDO; JANINI, LUIZ MARIO R.. HIV-1 Tropism Determines Different Mutation Profiles in Proviral DNA. PLoS One, v. 10, n. 9, . (09/14543-0)

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