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

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.

Reduced HIV-1 latent reservoir outgrowth and distinct immune correlates among women in Rakai, Uganda

“…If a larger proportion of proviruses were defective in females, the reduced QVOA viral outgrowth observed in females in this study would truly represent a smaller replication-competent reservoir. One prior study suggested that females have higher levels of hypermutation, but this finding warrants further investigation (22). Alternatively, females may have the same number of cells with replication-competent virus, but these cells may not reactivate as readily ex vivo.…”

Impact of Suboptimal APOBEC3G Neutralization on the Emergence of HIV Drug Resistance in Humanized Mice

“…Nonetheless, the extent to which APOBEC3-driven mutagenesis contributes to viral evolution and HIV/AIDS disease outcome in vivo remains controversial. Some clinical studies have found correlations between the frequency of G-to-A mutations in proviruses and plasma viral loads (7,74,76), whereas others failed to find such associations (17,75,77). Controlled experiments in cell culture, however, provide strong experimental evidence in support of the notion that A3G-driven mutagenesis facilitates HIV diversification and promotes escape from selection pressure (39,61,78).…”

Importance of Fc-mediated functions of anti-HIV-1 broadly neutralizing antibodies

“…Clearly, these studies indicate that the isotype of BnAbs can contribute significantly to protection from mucosal viral challenge, but the contribution of isotype might be epitope specific and too few studies have been conducted to determine how the antibody isotype contributes mechanistically to protection. Similar to IgG, IgA can engage its Fcα receptor that is present on the surfaces of monocytes, macrophages and neutrophils to mediate phagocytosis, respiratory burst, and the release of various cytokines and inflammatory mediators [ 89 ]. The potential of Fc/FcR interactions between IgA and Fcα receptor is an area of research that has not yet been fully explored in terms of its potential for combatting HIV -1.…”