Discordant Impact of HLA on Viral Replicative Capacity and Disease Progression in Pediatric and Adult HIV Infection

HLA class I polymorphism has a major influence on adult HIV disease progression. An important mechanism mediating this effect is the impact on viral replicative capacity (VRC) of the escape mutations selected in response to HLA-restricted CD8+ T-cell responses. Factors that contribute to slow progression in pediatric HIV infection are less well understood. We here investigate the relationship between VRC and disease progression in pediatric infection, and the effect of HLA on VRC and on disease outcome in adult and pediatric infection. Studying a South African cohort of >350 ART-naïve, HIV-infected children and their mothers, we first observed that pediatric disease progression is significantly correlated with VRC. As expected, VRCs in mother-child pairs were strongly correlated (p = 0.004). The impact of the protective HLA alleles, HLA-B*57, HLA-B*58:01 and HLA-B*81:01, resulted in significantly lower VRCs in adults (p<0.0001), but not in children. Similarly, in adults, but not in children, VRCs were significantly higher in subjects expressing the disease-susceptible alleles HLA-B*18:01/45:01/58:02 (p = 0.007). Irrespective of the subject, VRCs were strongly correlated with the number of Gag CD8+ T-cell escape mutants driven by HLA-B*57/58:01/81:01 present in each virus (p = 0.0002). In contrast to the impact of VRC common to progression in adults and children, the HLA effects on disease outcome, that are substantial in adults, are small and statistically insignificant in infected children. These data further highlight the important role that VRC plays both in adult and pediatric progression, and demonstrate that HLA-independent factors, yet to be fully defined, are predominantly responsible for pediatric non-progression

Essential food safety management points in the supply chain of game meat in South Africa

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Spoilage potential of a novel group of bacteria isolated from dairy products: research article

Cold-tolerant bacteria, also known as psychrotrophic bacteria, are notorious contaminants of milk in the refrigerated dairy food chain. These organisms, especially the pseudomonads, may produce heat-resistant enzymes that are responsible for the breakdown of proteins and lipids in milk and dairy products. Such reactions result in a variety of defects in the raw or unprocessed milk that may affect the suitability of such milk for further processing. The enzymes produced may cause defects in long-life dairy products such as cheese, butter and long-life milk. In the present study, a range of 18 yellow pigmented psychrotrophic bacteria, collectively known as flavobacteria, were isolated from local dairy products. One aim of this study was to identify these bacteria to species level using molecular techniques. A second aim was to determine the spoilage potential of these organisms based on profiles generated by the BIOLOG system (that may relate to hydrolytic enzymes produced). Of the 18 isolates, 14 belonged to the genus Chryseobacterium while 4 were identified as Empedobacter isolates. The most active spoilage organisms in this group were shown to be C. bovis, C. shigense and E. brevis. These findings illustrate that enzymatically catalysed defects in dairy products should not be attributed solely to acknowledged psychrotrophic bacteria such as the pseudomonads, but that flavobacterial species may also be actively involved

Consumer acceptability of a synbiotic version of the maize beverage mageu

This study examined the possibility of converting mageu, a fermented maize beverage popular throughout southern Africa, into a health-promoting and affordable alternative to probiotic dairy products. A range of probiotic Lactobacillus species was compared with a control species traditionally used to prepare mageu. Prebiotic oligosaccharide (soluble fibre), which enhances the growth of beneficial bacteria, was also included. The resulting beverages were compared in two ways: sensory attributes were determined by a trained panel using quantitative descriptive analysis (QDA), and consumer acceptability was assessed by 53 untrained volunteers. The QDA results suggest that mageu fermented by Lb. acidophilus or Lb. rhamnosus was most similar to the control mageu, while Lb. paracasei mageu and Lb. casei mageu were least similar. The consumer acceptability data confirmed that Lb. acidophilus or Lb. rhamnosus mageu did not differ significantly from the control, suggesting that either of these is suitable for commercial production of probiotic mageu

Chemical composition, storage stability and effect of cold-pressed flaxseed oil cake inclusion on bread quality

Abstract Flaxseed oil cake from a South African factory was screened for proximate composition, mineral content, fatty acid profile and storage stability. The oil cake was included at 10 and 15% levels (w/w) in brown bread and evaluated using a 96-member consumer panel. The oil cake contained between 38.0 and 47.3% protein, 12.8 and 26.1% crude fat and 3.7 and 5.1% ash. The total carbohydrates were mostly dietary fiber. Calcium, magnesium, phosphorus and potassium were in the range of 3.3 to 3.8, 4.8 to 5.9, 6.4 to 8.2 and 9.0 to 10.1 (mg/g), respectively. The oil from the flaxseed oil cake contained 58.5 to 59.7% of C18 omega-3 fatty acids. Peroxide levels of the flaxseed oil cake were below the threshold limits after 6 months storage. Thiobarbituric acid threshold values were exceeded after 5 months aerobic storage at 20C. Bread samples with inclusion levels of 10 and 15% flaxseed oil cake were acceptable to the consumer sensory panel

HLA-A*7401-mediated control of HIV viremia is independent of its linkage disequilibrium with HLA-B*5703.

The potential contribution of HLA-A alleles to viremic control in chronic HIV type 1 (HIV-1) infection has been relatively understudied compared with HLA-B. In these studies, we show that HLA-A*7401 is associated with favorable viremic control in extended southern African cohorts of &gt;2100 C-clade-infected subjects. We present evidence that HLA-A*7401 operates an effect that is independent of HLA-B*5703, with which it is in linkage disequilibrium in some populations, to mediate lowered viremia. We describe a novel statistical approach to detecting additive effects between class I alleles in control of HIV-1 disease, highlighting improved viremic control in subjects with HLA-A*7401 combined with HLA-B*57. In common with HLA-B alleles that are associated with effective control of viremia, HLA-A*7401 presents highly targeted epitopes in several proteins, including Gag, Pol, Rev, and Nef, of which the Gag epitopes appear immunodominant. We identify eight novel putative HLA-A*7401-restricted epitopes, of which three have been defined to the optimal epitope. In common with HLA-B alleles linked with slow progression, viremic control through an HLA-A*7401-restricted response appears to be associated with the selection of escape mutants within Gag epitopes that reduce viral replicative capacity. These studies highlight the potentially important contribution of an HLA-A allele to immune control of HIV infection, which may have been concealed by a stronger effect mediated by an HLA-B allele with which it is in linkage disequilibrium. In addition, these studies identify a factor contributing to different HIV disease outcomes in individuals expressing HLA-B*5703