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Title: In Vivo HIV-1 Hypermutation and Viral Loads Among Antiretroviral-Naive Brazilian Patients
Authors: Lima-Stein, Mariana Leao de [UNIFESP]
Alkmim, Wagner Tadeu [UNIFESP]
Souza Bizinoto, Maria Clara de [UNIFESP]
Lopez, Luis Fernandez
Burattini, Marcelo Nascimento
Maricato, Juliana Terzi [UNIFESP]
Giron, Leila [UNIFESP]
Araripe Sucupira, Maria Cecilia [UNIFESP]
Diaz, Ricardo Sobhie [UNIFESP]
Janini, Luiz Mario [UNIFESP]
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Issue Date: 1-Sep-2014
Publisher: Mary Ann Liebert, Inc
Citation: Aids Research and Human Retroviruses. New Rochelle: Mary Ann Liebert, Inc, v. 30, n. 9, p. 867-880, 2014.
Abstract: 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.
ISSN: 0889-2229
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