?????????Division of Medical Virology
Students
Rochelle Croucamp
Title: An investigation into Rocahepevirus ratti among rodents and shrews in South Africa.
Supervisor: Dr Tongai Maponga
Co-supervisor: Prof Wolfgang Preiser
This research project focuses on the detection of Rocahepevirus ratti (RHEV) in rodent and shrew populations across South Africa. Utilizing advanced molecular techniques, specifically quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays, this study aims to detect the presence of both RHEV and Paslahepevirus balayani in stored liver tissue samples. The findings will correlate the presence of these viruses with various host species and their geographical locations, providing a comprehensive overview of their distribution patterns. Testing for both viruses is crucial because they are zoonotic pathogens capable of infecting humans and have been detected in rodent populations. Currently, the distribution and transmission dynamics of RHEV in South Africa are poorly understood, limiting our knowledge of the virus's epidemiology and potential health impact. Therefore, this research will provide critical insights into the epidemiology of RHEV in South Africa. A better understanding of the distribution and transmission dynamics of these viruses will also aid in developing targeted interventions, particularly for immunocompromised individuals who are vulnerable to severe outcomes.?
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Tara-Lee von Mollendorff
Title: Investigating HIV Drug Resistance Profiles through High-Throughput Ion Torrent Sequencing Technology for Improved Antiretroviral Therapy Strategies
Supervisor: Prof Gert Van Zyl
Co-supervisor: Ms Mathilda Claassen
Dolutegravir in new HIV treatment regimens has shown low failure rates, but patients with prior treatment and virologic failure still face a high risk of drug resistance. HIV drug resistance (HIVDR) testing is crucial for patient management, and its future involves a shift from Sanger Sequencing to next-generation sequencing (NGS) methods. NGS offers advantages like detecting low abundance variants and potential cost-efficiency through sample pooling but faces challenges like high start-up costs and lengthy runtimes. The Ion-Torrent assay, using an AmpliSeq library panel, has various advantages in HIV drug resistance surveillance. The study aims to validate Ion-Torrent sequencing accuracy against Sanger Sequencing and proficiency panel standards. Additionally, the utility of Ion-Torrent NGS will be compared to Oxford Nanopore Technology Sequencing in terms of time, costs, and efficiency for routine drug resistance testing and surveillance. In the early stages of HIV-1 infection, infected CD4+ T cells migrate to the central nervous system (CNS) across the blood-brain barrier. Compartmentalization occurs due to limited antiretroviral drug penetration into the CNS, leading to prolonged accumulation of HIVDR mutations and poor ART response. Limited evidence exists for the utility of drug resistance testing in various body compartments. Env and Pol in blood plasma and cell-free cerebrospinal fluid will be compared, further exploring the application of drug resistance testing.?
Sarah Sallie
Title: Are warthogs (Phacochoerus africanus) infected by members of the genus Paslahepevirus?
Supervisor: Dr Tongai Maponga
Co-supervisor: Prof Wolfgang Preiser
Hepatitis E virus (HEV) has been shown in human beings as well as a wide range of animal species. HEV is widespread in domestic pigs Sus domesticus and wild boar Sus scrofa that are common sources of human infection but has not yet been identified in closely related warthogs Phacochoerus africanus. This study aims to determine whether warthogs may be infected by HEV. This will be achieved by testing warthog serum samples for HEV antibodies as a marker of past infection and for the presence of HEV genome as a marker of current infection. PCR-positive samples will undergo Oxford Nanopore Technologies (ONT) sequencing to characterize Paslahepevirus strains present. If tissue samples can also be obtained from infected warthogs, we would attempt isolating the virus using cell culture techniques which would allow further studying e.g., of the virus's pathogenesis. This research has the potential to contribute to agriculture by enhancing our understanding of zoonotic diseases and their implications for public health and food safety. By assessing the prevalence of HEV in warthogs and noting the species as a HEV reservoir, the agricultural sector can implement comprehensive strategies to minimize disease transmission.?
Nicky-Louise Byrne
Title: Undiagnosed viral infections in cerebrospinal fluid
Supervisor: Prof Gert van Zyl
Co-Supervisors: Prof Corena de Beer & Ms Mathilda Claassen
In South Africa, central nervous system (CNS) infections like meningitis in SUDI cases are underexplored. Cerebrospinal fluid (CSF) composition typically remains constant (Hrishi and Sethuraman, 2019), making its pathogen detection crucial. Investigation into the presence of Human Parechovirus (HPeV) -, Enterovirus (HeV) and Adenovirus (HAdV) in CSF specimens remain unexplored and underreported despite recent research implicating these viruses in CNS infections. A sensitive screening assay targeting conserved viral genome regions would increase the detection of these potentially underreported viruses in CSF. Assays targeting more hypervariable regions of the viral genome for HPeV and HeV would allow for the determination of molecular epidemiology. The study further has a stratified age sampling design to enrich for potentially interesting cases.?
Kayla Delaney
Title: Characterising HIV-1 reservoirs and evolution using a novel third-generation single genome sequencing approach
Main supervisor: Prof Gert van Zyl
Co-supervisors: Prof Mark Cotton and Prof Susan Engelbrecht
This project aims to investigate the evolution of the highly variable HIV-1 envelope, a target for alternative long-acting treatments such as broadly neutralising antibodies (bNAbs), in early treated infants. In addition, the presence of bNAb escape mutations present as minor variants which may lead to bNAb escape before treatment initiation may also be determined. This project further aims to elucidate whether persistent low-level viraemia can be explained by the presence of minor variants with drug resistance mutations in HIV-1 polymerase or by the presence of mutations outside of the drug gene target that confer resistance and are missed by conventional diagnostic assays.??
