Three of the PhDs produced by the College of Health Sciences revealed new mechanisms of HIV-1 immune control by the body and have laid a foundation for how to boost the immune system to overcome HIV through vaccination or novel therapies. Another has validated laboratory and clinical approaches for the rapid diagnosis of tuberculosis meningitis which, if implemented, will reduce costs and save lives.

The studies were conducted by Drs Ravesh Singh, Eshia Moodley-Govender, Dshanta Naicker and Vinod Patel, who graduated on 18 April.

Supervisor of all four projects, Professor Thumbi Ndung’u said the prospect of developing new antiretroviral drugs that target host and viral protein interactions has created a lot of excitement in the HIV research field.  ‘Dr Singh performed groundbreaking work to determine how novel immune factors known as TRIM ligases are regulated and to define how a replication cofactor known as cyclophilin A is regulated.  His work showed that some TRIM E3 ligases can potently block HIV infection and indicates that these factors may be good targets for novel immunotherapy to slow virus replication during HIV-1 infection,’ said Ndung’u.

Moodley-Govender conducted a study resulting in knowledge that may be important for HIV vaccines design to protect children born to HIV-1 infected mothers. It is suggested that in the absence of antiretroviral therapy, HIV infected children maintain high viral loads throughout infection and develop AIDS much faster than adults. Hence, this study investigated the biological determinants of viral control or lack of control in a rare untreated cohort of children.

Findings from the research revealed that genetic factors, immune responses and viral characteristics all contribute to HIV infection and disease outcomes in children.

Naicker conducted a study titled: “Effects and Mechanisms of Interleukin-10 Promoter Polymorphisms on HIV-1 Susceptibility and Pathogenesis” in which she investigated the role of interleukin 10 (IL-10), a powerful immunoregulatory chemical produced by immune cells in HIV infection. She showed in her thesis that IL-10 gene mutations that increase IL-10 levels may be beneficial in protecting against HIV-1 infection.

‘IL-10 may be detrimental during early HIV-1 infection but beneficial in chronic infection, possibly by reducing immune activation.  The mechanisms revealed in this work may help in rational use of IL-10 to boost HIV vaccines or to improve therapeutic strategies,’ said Ndung’u.

Focusing on tuberculosis meningitis (TBM) fuelled by the HIV epidemic, Patel investigated novel laboratory assays and clinical algorithms for the diagnosis of TBM.  A specialist neurologist, Patel’s work revealed novel tools that may aid in the rapid and cost-effective identification of TBM, reducing morbidity and mortality in high burden, resource-poor settings.

Ndung’u congratulated each candidate and encouraged them to continue with their research excellence, in line with the strategic goal of the College of Health Sciences at UKZN.

Ndung’u is Director for UKZN’s HIV Pathogenesis Programme and the Hasso Platner Research Laboratory, as well as Head of the Max Planck Research Institute for Infection Biology and the South African Research Chair in Systems Biology of HIV/AIDS.

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