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M van Niekerk

Publications and source records attributed to M van Niekerk.

6 recordsLinked to original sources
PubMed2003

Variation in the NS3 gene and protein in South African isolates of bluetongue and equine encephalosis viruses.

Bluetongue virus (BTV) and equine encephalosis virus (EEV) are agriculturally important orbiviruses transmitted by biting midges of the genus Culicoides. The smallest viral genome segment, S10, encodes two small nonstructural proteins, NS3 and NS3A, which mediate the release of virus particles from infected cells and may subsequently influence the natural dispersion of these viruses. The NS3 gene and protein sequences of South African isolates of these viruses were determined, analysed and compared with cognate orbivirus genes from around the world. The South African BTV NS3 genes were found to have the highest level of sequence variation for BTV (20 %), while the highest level of protein variation of BTV NS3 (10 %) was found between South African and Asian BTV isolates. The inferred NS3 gene phylogeny of the South African BTV isolates grouped them with BTV isolates from the United States, while the Asian BTV isolates grouped into a separate lineage. The level of variation found in the NS3 gene and protein of EEV was higher than that found for BTV and reached 25 and 17 % on the nucleotide and amino acid levels, respectively. The EEV isolates formed a lineage independent from that of the other orbiviruses. This lineage segregated further into two clusters that corresponded to the northern and southern regions of South Africa. The geographical distribution of these isolates may be related to the distribution of the Culicoides subspecies that transmit them.

African Horse Sickness Virus↗
PubMed2001

Membrane association of African horsesickness virus nonstructural protein NS3 determines its cytotoxicity.

The smallest RNA genome segment of African horsesickness virus (AHSV) encodes the nonstructural protein NS3 (24K). NS3 localizes in areas of plasma membrane disruption and is associated with events of viral release. Conserved features in all AHSV NS3 proteins include the synthesis of a truncated NS3A protein from the same open reading frame as that of NS3, a proline-rich region, a region of strict sequence conservation and two hydrophobic domains. To investigate whether these features are associated with the cytotoxicity of NS3 or altered membrane permeability, a series of mutants were constructed and expressed in the BAC-TO-BAC baculovirus-expression system. Our results indicate that mutations in either of the two hydrophobic domains do not prevent membrane targeting of the mutant proteins but abolish their membrane anchoring. This prevents their localization to the cell surface and obviates their cytotoxic effect. The cytotoxicity of NS3 is therefore dependent on its membrane topography and thus involves both hydrophobic domains. NS3 has many of the characteristics of lytic viral proteins that play a central role in viral pathogenesis through modifying membrane permeability.

African Horse Sickness Virus↗
PubMed2001

Variation of African horsesickness virus nonstructural protein NS3 in southern Africa.

NS3 protein sequences of recent African horsesickness virus (AHSV) field isolates, reference strains and current vaccine strains in southern Africa were determined and compared. The variation of AHSV NS3 was found to be as much as 36.3% across serotypes and 27.6% within serotypes. NS3 proteins of vaccine and field isolates of a specific serotype were found to differ between 2.3% and 9.7%. NS3 of field isolates within a serotype differed up to 11.1%. Our data indicate that AHSV NS3 is the second most variable AHSV protein, the most variable being the major outer capsid protein, VP2. The inferred phylogeny of AHSV NS3 corresponded well with the described NS3 phylogenetic clusters. The only exception was AHSV-8 NS3, which clustered into different groups than previously described. No obvious sequence markers could be correlated with virulence. Our results suggest that NS3 sequence variation data could be used to distinguish between field isolates and live attenuated vaccine strains of the same serotype.

African Horse Sickness Virus↗
PubMed2000

Vitamin A status in relation to electroretinographic and electrooculographic findings in HIV infection.

OBJECTIVES: To investigate the electrooculogram (EOG) and an expanded battery of electroretinograms (ERGs) in HIV-infected subjects without retinopathy at two different levels of immunosuppression. Consideration was given to the possible effects of serum levels of vitamin A. METHODS: Two groups of neurologically normal HIV-positive subjects with CD4+ cell counts of <200 (n=17) or >400 (n=19) were contrasted with 20 HIV-negative controls. Rod ERGs, oscillatory potentials and cone ERGs were obtained using ganzfeld stimulation. A sequence of dark- and light-adapted EOG recordings was analyzed to obtain light/dark ratios. The HIV-positive subjects underwent a comprehensive ophthalmologic examination. RESULTS: Intergroup comparisons failed to reveal any significant intergroup differences. Abnormal ERG findings, those exceeding the 98% confidence limits, occurred in 11% (4/36) of the HIV-positive subjects. One of these subjects was hyporetinemic and another had a subnormal retinol level. No subjects had abnormal EOGs. CONCLUSIONS: HIV infection influenced retinal function in 11% of a group of neurologically normal subjects without clinical signs of retinopathy. The profile of electrophysiological findings suggested predominant functional deficits involving middle or inner retinal layers. Vitamin A deficiency and possible vascular changes could account for the observed ERG abnormalities.

Adolescent↗
PubMed1994

The excretion of radiopharmaceuticals in human breast milk: additional data and dosimetry.

The amount of radioactivity excreted in breast milk following administration of 11 different radiopharmaceuticals, including technetium-99m labelled microspheres, pyrophosphate, diisopropyl-iminodiacetic acid (DISIDA) and sestamibi, has been measured. This report summarises the data collected from 60 patients. An effective decay constant for the series of samples from each patient was calculated from exponential curves fitted by least squares to the data. It is difficult to compare values from individual patients, since times of expression, volumes of milk and the activity administered are not uniform. In order to formulate reliable guidelines, we therefore calculated the total activity theoretically excreted in milk until complete decay of the radionuclide, which is usually higher than that actually measured over the actual period of collection. Of the various 99mTc compounds, pertechnetate clearly reaches the highest concentrations in breast milk. The wide variability of data from different patients who received the same radiopharmaceutical despite identical methods of sample collection and data processing confirms the impression gained from literature that transfer of radionuclides into milk varies greatly between individuals. Although we have calculated average values for each compound, very large standard deviations were obtained, and we believe that for radiation protection purposes, a "worst case" approach is the most appropriate. With new data available and the revision of ICRP recommendations, the guidelines applicable when radiopharmaceuticals are administered to breast-feeding mothers are reviewed. The effective dose resulting from close contact between patient and infant was included in these calculations. Breast feeding need not be interrupted after administration of 99mTc-DISIDA, -sulphur colloid, -gluconate and -methoxyisobutylisonitrile (MIBI). However, after administration of 99mTc-MIBI, close contact should be restricted. 99mTc-pyrophosphate and -microspheres require interruption periods of several hours. High activities of 99mTc-pertechnetate may require interruption longer than 2 days. For pertechnetate and 99mTc-labelled red blood cells, interruption of breast feeding with measurement of activity in expressed milk samples is recommended. Breast feeding is contra-indicated after administration of 67Ga and 131I. General guidelines regarding breast feeding after administration of radiopharmaceuticals are summarised.

Female↗