In Vivo HIV-1 Hypermutation and Viral Loads Among Antiretroviral-Naive Brazilian Patients

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art_LIMA-STEIN_In_Vivo_HIV1_Hypermutation_and_Viral_Loads_Among_2014.PDF (464.9 KB)
Citações na Scopus
5
Tipo de produção
article
Data de publicação
2014
Editora
MARY ANN LIEBERT, INC
DOI
Indexadores
Scopus
Web of Science
Título da Revista
ISSN da Revista
Título do Volume
Autores
LIMA-STEIN, Mariana Leao de
ALKMIM, Wagner Tadeu
BIZINOTO, Maria Clara de Souza
MARICATO, Juliana Terzi
GIRON, Leila
SUCUPIRA, Maria Cecilia Araripe
DIAZ, Ricardo Sobhie
JANINI, Luiz Mario
Autor de Grupo de pesquisa
Editores
Coordenadores
Organizadores
Citação
AIDS RESEARCH AND HUMAN RETROVIRUSES, v.30, n.9, p.867-880, 2014
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Hypermutation alludes to an excessive number of specific guanine-to-adenine (G- > A) substitutions in proviral DNA and this phenomenon is attributed to the catalytic activity of cellular APOBECs. Population studies relating hypermutation and the progression of infection by human immunodeficiency virus type 1 (HIV-1) have been performed to elucidate the effect of hypermutation on the natural course of HIV-1 infection. However, the many different approaches employed to assess hypermutation in nucleotide sequences render the comparison of results difficult. This study selected 157 treatment-naive patients and sought to correlate the hypermutation level of the proviral sequences in clinical samples with demographic variables, HIV-1 RNA viral load, and the level of CD4(+) T cells. Nested touchdown polymerase chain reaction (PCR) was performed with specific primers to detect hypermutation in the region of HIV-1 integrase, and the amplified sequences were run in agarose gels with HA-Yellow. The analysis of gel migration patterns using the k-means clustering method was validated by its agreement with the results obtained with the software Hypermut. Hypermutation was found in 31.2% of the investigated samples, and a correlation was observed between higher hypermutation levels and higher viral load levels. These findings suggest a high frequency of hypermutation detection in a Brazilian cohort, which can reflect a particular characteristic of this population, but also can result from the method approach by aiming at hypermutation-sensitive sites. Furthermore, we found that hypermutation events are pervasive during HIV-1 infection as a consequence of high viral replication, reflecting its role during disease progression.
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URI
https://observatorio.fm.usp.br/handle/OPI/8471
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MLS
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - LIM/01
Artigos e Materiais de Revistas Científicas - ODS/03