HIV Pathogenesis Programme Salutes its Graduates

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One of the major goals of the HIV Pathogenesis Programme (HPP) is to be a training programme that will invest in South Africans, enabling them to develop the expertise to be world leaders in the fields of basic and translational research.

This approach has resulted in three graduates (one PhD and three master’s) who will be graduated on the 6 May 2024.

Graduating with a PhD, Dr Zakithi Mkhize grew up with a love and passion for science. As a result, obtaining this PhD seemed the only natural course. She completed her master’s and PhD at HPP under the supervision of Dr Paradise Madlala (HPP Faculty Member and UKZN senior lecturer).

According to Mkhize, ‘Doing a PhD is like eating an elephant one bite at a time.’ Her research began by investigating the genetic variation of the transactivator of transcription (tat) during acute HIV-1 infection. The Tat plays an important role in HIV replication, where it binds to the transactivation response (TAR) element found in the HIV-1 promoter. Changes in Tats amino acid sequence affect its functionality. It has been shown that Tat also interacts with host transcription factors, most importantly the positive elongation factor b (P-TEFb). Further research focused on whether the presence of an Alanine at position 21 (TatA21), which has been shown to decrease functionality, affects its ability to bind to the TAR element and recruit the P-TEFb during replication. Results revealed that although TatA21 is able to efficiently recruit to the P-TEFb, its ability to bind the TAR element is lower than Tat with a Proline at position 21. This may explain the decreased functionality of TatA21. During her studies, Mkhize also had the opportunity to travel to two labs abroad: Gladstone Institute at the University of California, San Francisco; and Erasmus Medical Centre in the Netherlands where she learnt specialised techniques which assisted in the project and made lifelong collaborations.

She said, ‘Grabbing opportunities which came my way during my PhD played a huge role in my success. My passion for science communication also made me the regional winner of the FameLab competition in 2021 and this propelled me to heights I could have never imagined. I will continue to be a Black Girl Scientist and advocate for all the Black women scientists out there.’

Ms Thandeka Khubeka born and raised at Manzana farm, Newcastle, KwaZulu-Natal, will be graduating with a master’s degree. Her science journey began in 2017 with a Bachelor of Science degree, majoring in Microbiology and Biochemistry at the University of KwaZulu-Natal. In 2021, Thandeka completed her Honours in Medical Microbiology at UKZN. That research looked at HIV-1 Nef-mediated SERINC5 downregulation for therapeutic vaccines. That’s when she discovered her interest in HIV research that will contribute to the prevention, diagnosis and treatment of HIV, which affects millions of people. She was then given an opportunity at the HIV Pathogenesis Programme (HPP) to pursue her master’s degree under the supervision of Dr Nompumelelo P Mkhwanazi (HPP Faculty Member and UKZN lecturer). Thandeka was encouraged by the saying: “It’s now or never, so make up your mind” whenever in doubt or discouraged during the master’s journey. Her study investigated the evolution of HIV-1 anti-Tat antibodies from HIV-1 early treated individuals using ELISA and associate them with the size of the reservoirs, immune activation and also investigated how the HIV-1 Tat protein impacts the anti-Env antibody neutralisation ability. These findings suggested that Tat-specific IgM and IgG antibodies in combination with cART could be a better strategy to improve HIV-1 vaccine. This work is currently under review for publication.

She said: ‘I want to recognise and express my sincere gratitude to my supervisor, Dr Nompumelelo P Mkhwanazi, whose support made this work achievable. Her guidance and advice carried me through all the stages of writing my project. I also want to extend heartfelt appreciation to Professor Thumbi Ndung’u for his support, help, and brilliant comments and suggestions. The journey was not easy but by God’s grace and all the support I got from my family and the HPP team made everything possible.’

Also supervised by Dr Nompumelelo P Mkhwanazi, Ms Mbali Kubheka will be graduating with a master’s degree. After completing her BSc Honours in Medical Biochemistry, Mbali joined HPP in January 2022. Her work focused on anti-HIV and Immunomodulatory Properties of the Fractionated Crude Extracts Isolated from Alternaria alternata. This novel research was presented at the South African AIDS Conference in June last year by Mbali. In addition, her research findings are submitted for publication in the Microorganism journal.

Another master’s graduate, a Durban native Ms Suhina Sirkisson has always been interested in human genetics and physiology. After high school, she earned a scholarship to Stellenbosch University, achieving a BSc in Physiology and Psychology, with a minor in Genetics, and continued to complete a BSc Honours in Physiology.

‘Serendipity led me to the HPP. HPP’s work aligned with the forefront of HIV research and offered an opportunity to deepen my understanding of and burgeoning interest in human pathology while learning new and relevant techniques prevalent in this field.’

Initially under the guidance and supervision of Dr Katlego Sojane and, later, Dr Bongiwe Ndlovu (HPP Faculty Member and UKZN senior lecturer), the focus of Sirkisson’s research was aimed at determining and comparing the coreceptor usage of HIV-1 subtype C in Cryptococcal Meningitis (CM) chronically co-infected participants, between the central nervous system (represented by cerebrospinal fluid) and the peripheral blood (represented by plasma). Another objective was to identify genotypic characteristics (motifs or sequences) associated with the observed coreceptor usage profiles and to evaluate the accuracy of Coreceptor Prediction Algorithms (CPAs) in predicting this usage.

These findings improved the understanding of coreceptor prevalence, particularly CCR3 and CXCR4, in South African CM co-infected patients. These findings have implications for the eligibility of these patients for coreceptor-targeted therapies like Maraviroc and the reliability of Coreceptor Prediction Algorithms (CPAs) in this context. This clarifies the eligibility of South African CM co-infected patients for coreceptor-targeted therapies like Maraviroc by revealing the accuracy of Coreceptor Prediction Algorithms (CPAs) in this context.

According to Sirkisson, ‘In addition to the technical skills I developed, I experienced significant personal growth. The COVID-19 pandemic challenged my resilience, adaptability, confidence, and flexibility. I learned to truly “expect the unexpected” and developed a newfound strength and perseverance. My master’s journey cultivated remarkable resilience and a knack for navigating seemingly impossible situations, which has become a cornerstone of my skillset. R Collier’s quote, “Success is the sum of small efforts, repeated” perfectly reflects my master’s journey.’

HPP is incredibly proud of these outstanding students and wish them every success in their future endeavours.

Words: NdabaOnline

Photograph: Sethu Dlamini