Manipulation of Human Immunodeficiency Virus Restriction Factors: RPRD2, SERINC3 and SERINC5

Background: There is a need for a newer approach to tackle human immunodeficiency virus (HIV) due to limitations of the current antiretrovirals, innate cell restriction factors offer such opportunity. This study seeks to characterise three novel HIV restriction factors and explore their therapeutic potentials. Methods: Jurkat cell line was treated with polyinosinic-polycytidylic acid (poly I:C), a toll-like receptor-3 agonist (TLR3), at different concentrations (5 µg/ml, 10 µg/ml, 20 µg/ml) and (4 µg/ml, 8 µg/ml, 12 µg/ml) and untreated controls. Its effects on cellular proliferation were observed over many hours. A bioinformatic search of Regulation of nuclear pre-mRNA domain-containing 2 (RPRD2) and Serine incorporator 3 and 5 (SERINC3 and SERINC5) were conducted to predict for nuclear localisation signal (NLS) and potential ubiquitination and Sumoylation sites in the proteins using online NLS Mapper, UbPred and GPS-SUMO tools respectively. Small interference RNA (siRNA) transfection of Jurkat cell line was done to knockdown karyopherin alpha 2 (KPNA2) using Lipofectamine 3000. Western blot analysis was done to assess transfection efficiency. Results: Jurkat cells treated with 5 µg/ml, 10 µg/ml and 20 µg/ml proliferated more than the control while those treated with 4 µg/ml, 8 µg/ml and 12 µg/ml proliferated less with statistical significance between the untreated and 4 µg/ml concentration at 72 hours (p = 0.021).RPRD2 was the only protein that has NLS (RDPFHSLKRPRPPFARGPPFFAPKRPFFP)at position 1430 with a score of 9.8. RPRD2 has a site predicted each for SUMO interaction and sumoylation consensus (p = 0.022), SERINC3 had six sites for SUMO interactions and 2 for sumoylation non-consensus, all with no statistical significance and SERINC5 has a significant SUMO interaction site at position 44-48 (p = 0.049). The predicted ubiquitination sites for RPRD2 were 44 (ten with high, 27 with medium and seven with low confidence respectively), SERINC3 had four sites (two with medium and low confidence each) and SERINC5 had three (one with high, medium and low confidence each). The KPNA2 knockdown was not successful. Conclusion: HIV restriction factors present a potential therapeutic target; adequate characterisation of these proteins is important towards fashioning drugs in this regard. Keywords: Toll-like receptor 3, Polyinosinic-polycytidylic acid (poly I:C), Nuclear localisation signal, Sumoylation, Ubiquitination, Karyopherin alpha 2 (KPNA2

Use of long-acting injectable antiretroviral agents for human immunodeficiency Virus: A review

The development of potent antiretroviral drugs has significantly reduced morbidity and mortality associated with human immunodeficiency virus infection, however, the effectiveness of these medications depends upon consistent daily oral intake. Non-adherence can lead to the emergence of resistance, treatment failure and disease progression. This has necessitated the development of long-acting antiretroviral formulations administrable via an infrequent dosing regimen. Long-acting injectable forms of cabotegravir and rilpivirine have reached various stages in clinical trials both for the treatment and prevention of HIV. Other long-acting agents are at various stages of development. This review evaluates the current research on the development of long-acting injectable antiretroviral agents for the treatment and prevention of HIV

Challenges of Residency Training and Early Career Doctors in Nigeria Phase II: Update on Objectives, Design, and Rationale of Study

Background: Early career doctors (ECDs) are a dynamic and highly mobile group of medical and dental practitioners who form a significant proportion of the health workforce in Nigeria. The challenges of residency training and ECDs in Nigeria CHARTING Phase I study explored limited challenges affecting ECDs under the broad themes of demography, workplace issues, and psychosocial issues. The CHARTING II was expanded to provide wider insight into the challenges of ECDs in Nigeria. Objective: This protocol aims to provide clear objectives including description of objectives, design, and rationale for the conduct of the proposed CHARTING II study which seeks to explore other components under the various themes of demographic, workplace, psychosocial issues affecting the ECDs in Nigeria, and which were not explored under CHARTING I.   Methodology: This shall be a mixed study design that will combine qualitative and quantitative methods, to investigate 27 subthemes among 2000 ECDs spread across 31 centers, accredited by the Nigerian Association of Resident Doctors. Participants shall be selected using the multistage sampling method. The primary data will be generated using structured proforma and validated questionnaires,while administrative sources would serve as a source of secondary data. Data will be entered and analyzed using appropriate statisticalsoftware. Conclusion: CHARTING II study would provide more robust data and insight into the problems encountered by ECDs in Nigeria. This would in turn build a platform for institutional engagement and advocacy in order to drive relevant policies to mitigate these challenges. Keywords: Early career doctors, Nigeria, residency, resident doctors, trainin

Use of long-acting injectable antiretroviral agents for human immunodeficiency Virus: A review

From Elsevier via Jisc Publications RouterHistory: accepted 2021-11-21, epub 2021-12-06, issued 2022-01-31Article version: AMPublication status: PublishedFunder: authorsThe development of potent antiretroviral drugs has significantly reduced morbidity and mortality associated with human immunodeficiency virus infection, however, the effectiveness of these medications depends upon consistent daily oral intake. Non-adherence can lead to the emergence of resistance, treatment failure and disease progression. This has necessitated the development of long-acting antiretroviral formulations administrable via an infrequent dosing regimen. Long-acting injectable forms of cabotegravir and rilpivirine have reached various stages in clinical trials both for the treatment and prevention of HIV. Other long-acting agents are at various stages of development. This review evaluates the current research on the development of long-acting injectable antiretroviral agents for the treatment and prevention of HIV