Gag-protease driven viral replication capacity among HIV-1 subtypes: Implications for disease progression, epidemic spread and vaccine design.

Doctoral Degree. University of KwaZulu-Natal, Durban.The HIV-1 epidemic in sub-Saharan Africa is heterogeneous with diverse unevenly distributed subtypes and regional differences in prevalence. Subtype-specific differences in disease progression rate and transmission efficiency have been reported, but the underlying biological mechanisms have not been fully characterized. In this study, I tested the hypothesis that the subtypes prevalent in the East African epidemic, where adult prevalence rate is higher, have lower viral replication capacity (VRC) than their West African counterparts where adult prevalence rates are lower. Materials and methods: Gag-protease sequencing was performed on plasma samples from 213 and 160 antiretroviralnaïve participants from West and East Africa, respectively. Online bioinformatic tools were used to infer HIV-1 subtypes and recombination patterns. Replication capacities of patientderived gag-protease chimeric viruses from West (n=178) and East (n=114) Africa were determined using a green fluorescent protein reporter-based cell assay. Subtype and regional differences in viral replication capacity and amino acid variants impacting replication capacity were identified using appropriate statistical methods. Results: Subtypes identified in West Africa were CRF02_AG (65%, n=139), G (7%, n=15), A3 (5%, n=10), other CRFs (12%, n=26), various pure subtypes (9%, n=19) and A1G recombinants (2%, n=4). Subtypes A1 (64%, n=103), D (22%, n=35), AD (11%, n=17) and AC (3%, n=5) were identified in East Africa. Chimeric viruses from West Africa had significantly higher VRC compared to those from East Africa (p < 0.0001), with subtype-specific differences found among strains within West and East Africa (p < 0.0001). Recombination patterns showed a preference for subtypes D, G or J rather than subtype A in the p6 region of gag, with evidence that subtype-specific differences in this region impact viral replication capacity. Furthermore, the Gag A83V polymorphism was associated with reduced viral replication capacity in CRF02_AG (median < 0.86). HLA-A*23:01 (p = 0.0014) and HLA-C*07:01 (p = 0.002) were associated with significantly lower viral replication capacity in subtype A infected individuals from East Africa. Conclusion: Overall, the data showed that viruses from West Africa displayed higher replication capacity than those from East Africa, which is consistent with the hypothesis that lower viral replication capacity is associated with higher population prevalence.Author's keywords: HIV-1 subtypes, Viral replication capacity, Sub-Saharan Africa, Circulating recombinant form, HLA

Subtype-specific differences in Gag-protease replication capacity of HIV-1 isolates from East and West Africa

Abstract Background The HIV-1 epidemic in sub-Saharan Africa is heterogeneous with diverse unevenly distributed subtypes and regional differences in prevalence. Subtype-specific differences in disease progression rate and transmission efficiency have been reported, but the underlying biological mechanisms have not been fully characterized. Here, we tested the hypothesis that the subtypes prevalent in the East Africa, where adult prevalence rate is higher, have lower viral replication capacity (VRC) than their West African counterparts where adult prevalence rates are lower. Results Gag-protease sequencing was performed on 213 and 160 antiretroviral-naïve chronically infected participants from West and East Africa respectively and bioinformatic tools were used to infer subtypes and recombination patterns. VRC of patient-derived gag-protease chimeric viruses from West (n = 178) and East (n = 114) Africa were determined using a green fluorescent protein reporter-based cell assay. Subtype and regional differences in VRC and amino acid variants impacting VRC were identified by statistical methods. CRF02_AG (65%, n = 139), other recombinants (14%, n = 30) and pure subtypes (21%, n = 44) were identified in West Africa. Subtypes A1 (64%, n = 103), D (22%, n = 35), or recombinants (14%, n = 22) were identified in East Africa. Viruses from West Africa had significantly higher VRC compared to those from East Africa (p < 0.0001), with subtype-specific differences found among strains within West and East Africa (p < 0.0001). Recombination patterns showed a preference for subtypes D, G or J rather than subtype A in the p6 region of gag, with evidence that subtype-specific differences in this region impact VRC. Furthermore, the Gag A83V polymorphism was associated with reduced VRC in CRF02_AG. HLA-A*23:01 (p = 0.0014) and HLA-C*07:01 (p = 0.002) were associated with lower VRC in subtype A infected individuals from East Africa. Conclusions Although prevalent viruses from West Africa displayed higher VRC than those from East Africa consistent with the hypothesis that lower VRC is associated with higher population prevalence, the predominant CRF02_AG strain in West Africa displayed higher VRC than other prevalent strains suggesting that VRC alone does not explain population prevalence. The study identified viral and host genetic determinants of virus replication capacity for HIV-1 CRF02_AG and subtype A respectively, which may have relevance for vaccine strategies

Comprehensive Data via Spectroscopy and Molecular Dynamics of Chemically Treated Graphene Nanoplatelets

Graphene nanoplatelets (GnPs) are promising candidates for gas sensing applications because they have a high surface area to volume ratio, high conductivity, and a high temperature stability. The information provided in this data article will cover the surface and structural properties of pure and chemically treated GnPs, specifically with carboxyl, ammonia, nitrogen, oxygen, fluorocarbon, and argon. Molecular dynamics and adsorption calculations are provided alongside characterization data, which was performed with Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) to determine the functional groups present and effects of those groups on the structural and vibrational properties. Certain features in the observed Raman spectra are attributed to the variations in concentration of the chemically treated GnPs. XRD data show smaller crystallite sizes for chemically treated GnPs that agree with images acquired with scanning electron microscopy. A molecular dynamics simulation is also employed to gain a better understanding of the Raman and adsorption properties of pure GnPs

Experimental Spectroscopic Data of SnO2 Films and Powder

Powders and films composed of tin dioxide (SnO2) are promising candidates for a variety of high-impact applications, and despite the material&rsquo;s prevalence in such studies, it remains of high importance that commercially available materials meet the quality demands of the industries that these materials would most benefit. Imaging techniques, such as scanning electron microscopy (SEM), atomic force microscopy (AFM), were used in conjunction with Raman spectroscopy and X-ray photoelectron spectroscopy (XPS) to assess the quality of a variety of samples, such as powder and thin film on quartz with thicknesses of 41 nm, 78 nm, 97 nm, 373 nm, and 908 nm. In this study, the dependencies of the corresponding Raman, XPS, and SEM analysis results on properties of the samples, like the thickness and form (powder versus film) are determined. The outcomes achieved can be regarded as a guide for performing quality checks of such products, and as reference to evaluate commercially available samples

Experimental Spectroscopic Data of SnO₂ Films and Powder

Powders and films composed of tin dioxide (SnO2) are promising candidates for a variety of high-impact applications, and despite the material’s prevalence in such studies, it remains of high importance that commercially available materials meet the quality demands of the industries that these materials would most benefit. Imaging techniques, such as scanning electron microscopy (SEM), atomic force microscopy (AFM), were used in conjunction with Raman spectroscopy and X-ray photoelectron spectroscopy (XPS) to assess the quality of a variety of samples, such as powder and thin film on quartz with thicknesses of 41 nm, 78 nm, 97 nm, 373 nm, and 908 nm. In this study, the dependencies of the corresponding Raman, XPS, and SEM analysis results on properties of the samples, like the thickness and form (powder versus film) are determined. The outcomes achieved can be regarded as a guide for performing quality checks of such products, and as reference to evaluate commercially available samples