Nef performs multiple cellular activities that enhance HIV-1 pathogenesis. The role of Nef-mediated down-regulation of the host restriction factor SERINC5 in HIV-1 pathogenesis is not well-defined. We aimed to investigate if SERINC5 down-regulation activity contributes to HIV-1 subtype C disease progression, to assess the relative contribution of this activity to overall Nef function, and to identify amino acids required for optimal activity. We measured the SERINC5 down-regulation activity of 106 subtype C Nef clones, isolated from individuals in early infection, for which the Nef activities of CD4 and HLA-I down-regulation as well as alteration of TCR signalling were previously measured. The relationship between SERINC5 down-regulation and markers of disease progression, and the relative contribution of SERINC5 down-regulation to a Nef fitness model-derived E value (a proxy for overall Nef fitness in vivo), were assessed. No overall relationship was found between SERINC5 down-regulation and viral load set point (p = 0.28) or rate of CD4+ T cell decline (p = 0.45). CD4 down-regulation (p = 0.02) and SERINC5 down-regulation (p = 0.003) were significant determinants of E values in univariate analyses, with the greatest relative contribution for SERINC5 down-regulation, and only SERINC5 down-regulation remained significant in the multivariate analysis (p = 0.003). Using a codon-by-codon analysis, several amino acids were significantly associated with increased (10I, 11V, 38D, 51T, 65D, 101V, 188H and, 191H) or decreased (10K, 38E, 65E, 135F, 173T, 176T and, 191R) SERINC5 down-regulation activity. Site-directed mutagenesis experiments of selected mutants confirmed a substantial reduction in SERINC5 down-regulation activity associated with the mutation 173T, while mutations 10K, 135F, and 176T were associated with more modest reductions in activity that were not statistically significant. These results suggest that SERINC5 down-regulation is a significant contributor to overall Nef function and identify potential genetic determinants of this Nef function that may have relevance for vaccines or therapeutics.
Emerging highly transmissible viral infections such as SARS-CoV-2 pose a significant global threat to human health and the economy. Since its first appearance in December 2019 in the city of Wuhan, Hubei province, China, SARS-CoV-2 infection has quickly spread across the globe, with the first case reported on the African continent, in Egypt on February 14th, 2020. Although the global number of COVID-19 infections has increased exponentially since the beginning of the pandemic, the number of new infections and deaths recorded in African countries have been relatively modest, suggesting slower transmission dynamics of the virus on the continent, a lower case fatality rate, or simply a lack of testing or reliable data. Notably, there is no significant increase in unexplained pneumonias or deaths on the continent which could possibly indicate the effectiveness of interventions introduced by several African governments. However, there has not yet been a comprehensive assessment of sub-Saharan Africa’s (SSA) preparedness and response to the COVID-19 pandemic that may have contributed to prevent an uncontrolled outbreak so far. As a group of early career scientists and the next generation of African scientific leaders with experience of working in medical and diverse health research fields in both SSA and resource-rich countries, we present a unique perspective on the current public health interventions to fight COVID-19 in Africa. Our perspective is based on extensive review of the available scientific publications, official technical reports and announcements released by governmental and non-governmental health organizations as well as from our personal experiences as workers on the COVID-19 battlefield in SSA. We documented public health interventions implemented in seven SSA countries including Uganda, Kenya, Rwanda, Cameroon, Zambia, South Africa and Botswana, the existing gaps and the important components of disease control that may strengthen SSA response to future outbreaks.
Emerging highly transmissible viral infections such as SARS-CoV-2 pose a significant global threat to human health and the economy Since its first appearance in December 2019 in the city of Wuhan, Hubeprovince, China, SARS-CoV-2 infection has quickly spread across the globe, with the first case reported on the African continent, in Egypt on February 14th, 2020 Although the global number of COVID-19 infections has increased exponentially since the beginning of the pandemic, the number of new infections and deaths recorded in African countries have been relatively modest, suggesting slower transmission dynamics of the virus on the continent, a lower case fatality rate, or simply a lack of testing or reliable data Notably, there is no significant increase in unexplained pneumonias or deaths on the continent which could possibly indicate the effectiveness of interventions introduced by several African governments However, there has not yet been a comprehensive assessment of sub-Saharan Africa’s (SSA) preparedness and response to the COVID-19 pandemic that may have contributed to prevent an uncontrolled outbreak so far As a grouof early career scientists and the next generation of African scientific leaders with experience of working in medical and diverse health research fields in both SSA and resource-rich countries, we present a unique perspective on the current public health interventions to fight COVID-19 in Africa Our perspective is based on extensive review of the available scientific publications, official technical reports and announcements released by governmental and non-governmental health organizations as well as from our personal experiences as workers on the COVID-19 battlefield in SSA We documented public health interventions implemented in seven SSA countries including Uganda, Kenya, Rwanda, Cameroon, Zambia, South Africa and Botswana, the existing gaps and the important components of disease control that may strengthen SSA response to future outbreaks
Emerging highly transmissible viral infections such as SARS-CoV-2 pose a significant global threat to human health and the economy. Since its first appearance in December 2019 in the city of Wuhan, Hubei province, China, SARS-CoV-2 infection has quickly spread across the globe, with the first case reported on the African continent, in Egypt on February 14th, 2020. Although the global number of COVID-19 infections has increased exponentially since the beginning of the pandemic, the number of new infections and deaths recorded in African countries have been relatively modest, suggesting slower transmission dynamics of the virus on the continent, a lower case fatality rate, or simply a lack of testing or reliable data. Notably, there is no significant increase in unexplained pneumonias or deaths on the continent which could possibly indicate the effectiveness of interventions introduced by several African governments. However, there has not yet been a comprehensive assessment of sub-Saharan Africa’s (SSA) preparedness and response to the COVID-19 pandemic that may have contributed to prevent an uncontrolled outbreak so far. As a group of early career scientists and the next generation of African scientific leaders with experience of working in medical and diverse health research fields in both SSA and resource-rich countries, we present a unique perspective on the current public health interventions to fight COVID-19 in Africa. Our perspective is based on extensive review of the available scientific publications, official technical reports and announcements released by governmental and non-governmental health organizations as well as from our personal experiences as workers on the COVID-19 battlefield in SSA. We documented public health interventions implemented in seven SSA countries including Uganda, Kenya, Rwanda, Cameroon, Zambia, South Africa and Botswana, the existing gaps and the important components of disease control that may strengthen SSA response to future outbreaks.
Emerging highly transmissible viral infections such as SARS-CoV-2 pose a significant global threat to human health and the economy. Since its first appearance in December 2019 in the city of Wuhan, Hubei province, China, SARS-CoV-2 infection has quickly spread across the globe, with the first case reported on the African continent, in Egypt on February 14th, 2020. Although the global number of COVID19 infections has increased exponentially since the beginning of the pandemic, the number of new infections and deaths recorded in African countries have been relatively modest, suggesting slower transmission dynamics of the virus on the continent, a lower case fatality rate, or simply a lack of testing or reliable data. Notably, there Open Peer Review
Phytotherapeutic treatments have been on the ascendancy over the years as the quest for alternate and easily accessible health care is on the rise. Tulbaghia acutiloba has been used by both traditional healers and the South African population for the management of chronic conditions, but lacks scientific authentication. Hydro-methanolic extracts (roots, rhizomes, leaves and flowers) of the plant were evaluated for their antioxidant activities, biochemical and phytochemical profile. Additionally, the heavy metal content and antihypertensive effects including Angiotensin 1-Converting Enzyme Inhibitory (ACEI) activities were investigated. The antioxidant ability of the hydro-methanolic extracts were determined by 2, 2- diphenyl-1-picryl hydrazyl ( DPPH ), hydrogen peroxide and nitric oxide scavenging activities. Phytochemical profile was assessed using qualitative and quantitative methods whereas the heavy metal toxicity was determined by using Inductively- Coupled Plasma-Optical Emission Spectrometry (ICP-OES). In vitro ACEI activity was determined by the hydrolysis of the tripeptide, hippuryl –L-Histidyl-L-leucine (Hip-His-Leu ). All the extracts showed potent antioxidant activities which was concentration dependent. Phytochemical analysis showed the presence of phenols, amino acids and alkaloids in all the extracts. The leaves showed a relatively higher total phenolic content of 43.26±1.15 mgGAE/g. Gas Chromatography–Mass Spectrometry (GC-MS) analysis showed the presence of major compounds such as α-linolenic acid in the leaves as well as oleic acid and palmitic acid in other parts of the plants. Toxicity of heavy metal was undetected in all extracts of the plant. All the extracts of the plants showed a >50% ACE inhibition at different concentrations with the leaves showing a relatively higher inhibitory activity (76.66 ± 1.65, IC50 ; 154.23 μg/ml) compared with the other parts of the plants. It is therefore concluded in this study that the biological activities and phytochemical component of the hydro-methanolic extracts of T. acutiloba is indicative of its possible use for the treatment as well as prevention of hypertension and oxidative stressrelated diseases.
This study describes the geochemical and physico-chemical characterization of contaminant status of six wetlands of the lower uMngeni River floodplain, KwaZulu-Natal Province, South Africa. At all sites, organic matter content, calcium carbonate and metal concentrations were highest within the fine-sediment dominated surface laminae, decreasing with depth. Exceptions were displayed by arsenic (As), nickel (Ni) and vanadium (V), presumed to be derived from normal geochemical processes. Geochemical indicies indicated high contamination factors for lead (Pb) and V, pointing to moderate anthropogenic metal pollution contribution. Most conspicuous are the contamination high factors for Pb across most sites. Fe and Pb contamination is ubiquitous in all surface laminae, with contamination factors being either border-line, moderate or of high contamination. Enrichment factors for As, Mn and P at site S6 indicate possible anthropogenic sources. The data also shows a possibility of anthropogenic input of P and Zn at site S3. Apart from the enrichment factors established for Ni across all sites, all other metals indicate some degree of enrichment. A range of variable results for the mid to deeper laminae are indicative of natural processes with some human influence. Results of ANOVA confirm the above. Principal component analysis reveals a 46.4% variance from component 1 elements (Al, Ca, Cr, Cu, Fe, Mg, Mn and Zn) and a 17.8% variance from component 2 (Al, Cu and Fe). Given the rapid rate of development in this region, the protection of these floodplain wetlands must receive high conservation priority from the local municipality.