Biology subjects

Louw, J.

Publications and source records attributed to Louw, J..

3 recordsLinked to original sources

bioRxiv2021

Molecular insights into antibody-mediated protection against the prototypic simian immunodeficiency virus

SIVmac239 infection of macaques is a favored model of human HIV infection. However, the SIVmac239 envelope (Env) trimer structure, glycan occupancy, and the targets and ability of neutralizing antibodies (nAbs) to protect against SIVmac239 remain unknown. Here, we report the isolation of SIVmac239 nAbs that recognize a glycan hole and the V1/V4 loop. A high-resolution structure of a SIVmac239 Env trimer-nAb complex shows many similarities to HIV and SIVcpz Envs, but with distinct V4 features and an extended V1 loop. Moreover, SIVmac239 Env has a higher glycan shield density than HIV Env that may contribute to poor or delayed nAb responses in SIVmac239-infected macaques. Passive transfer of a nAb protects macaques from repeated low dose intraveneous SIVmac239 challenge at serum titers comparable to those described for protection of humans against HIV infection. Our results provide structural insights for vaccine design and shed light on antibody-mediated protection in the SIV model.

immunology↗

bioRxiv2020

Human Whole Genome Sequencing in South Africa

The advent and evolution of next generation sequencing has considerably impacted genomic research. Until recently, South African researchers were unable to access affordable platforms capable of human whole genome sequencing locally and DNA samples had to be exported. Here we report the whole genome sequences of the first six human DNA samples sequenced and analysed at the South African Medical Research Council Genomics Centre. We demonstrate that the data obtained is of high quality, with an average sequencing depth of 36.41, and that the output is comparable to data generated internationally on a similar platform. The Genomics Centre creates an environment where African researchers are able to access world class facilities, increasing local capacity to sequence whole genomes as well as store and analyse the data.Competing Interest StatementThe authors have declared no competing interest.View Full Text

genomics↗

bioRxiv2019

Palmitate-induced toxicity is associated with impaired mitochondrial respiration and accelerated oxidative stress in cultured cardiomyocytes: the critical role of Coenzyme Q9/10

Impaired mitochondrial function concomitant to enhanced oxidative stress-induced damage are well established mechanisms involved in hyperlipidemia-induced cardiotoxicity. Coenzyme Q9/10 (CoQ) is known to be a critical component of the mitochondrial electron transport chain that efficiently supports the process of bioenergetics in addition to its antioxidant activities. However, there is very limited information on the direct effect of myocardial lipid overload on endogenous CoQ levels in association with mitochondrial respiration and oxidative stress status. Here, such effects were explored by exposing H9c2 cardiomyocytes to various doses (0.15 to 1 mM) of palmitate for 24 hours. The results demonstrated that palmitate doses [≥] 0.25 mM are enough to impair mitochondrial respiration and cause oxidative stress. Although endogenous CoQ levels are enhanced by palmitate doses [≤] 5 mM, this is not enough to counteract oxidative stress, but is sufficient to maintain cell viability of cardiomyocytes, suggesting a compensation mechanism. Palmitate doses > 5 mM caused severe mitochondrial toxicity, including reduction of cell viability. Interestingly, enhancement of CoQ levels with the lowest dose of palmitate (0.15 mM) was accompanied by a significantly reduction of CoQ oxidation status, as well as low cytosolic production of reactive oxygen species. From the overall findings, it appears that CoQ response may be crucial to improve mitochondrial function and thus protect against hyperlipidemia-induced insult. These results further suggest that therapeutic agents that can stimulate endogenous levels of CoQ may be beneficial in protecting the myocardium against diabetes associated complications.

biochemistry↗