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UKZN students advance HIV research in Africa

April 24, 2012

Research conducted by seven students at UKZN’s HIV Pathogenesis Programme (HPP) has shed new light on how HIV is transmitted and either manifests itself or is brought under control by the immune system. Five of the students have graduated with PhDs while the other two attained Master of Medical Science degrees. The PhD students are Dr Jaclyn Wright, Dr Christina Thobakgale, Dr Derseree Archary, Dr Paradise Madlala and Dr Danni Ramduth. Mr Bongiwe Ndlovu and Mr Shivan Chetty received Masters degrees.

Pioneering HIV research in Africa are five PhD graduates from UKZN's HIV Pathogenesis Programme,
Dr Christina Thobakgale; Dr Derseree Archary; Dr Paradise Madlala; Supervisor and Head of HPP,
Professor Thumbi Ndung'u; Dr Danni Ramduth and Dr Jaclyn Wright.

 

Wright investigated the impact of immune-driven Sequence variation in human immunodeficiency virus type 1 (HIV-1) infection subtype C Gag-Protease on viral fitness and disease progression. Gag is an important viral protein that the virus needs to replicate in human cells. 

 

Wright found that HLA proteins associated with slower HIV-1 disease progression selected for slower HIV-1 replication capacity through driving mutations in Gag. The data supports the concept of an HIV-1 vaccine in which immune responses are directed towards several conserved regions of HIV-1 Gag with the aim to constrain immune escape mutations and slow HIV-1 replication thereby resulting in slower disease progression. Slower disease progression results in reduced HIV-1 transmission in the population.

 

Wright said: ‘I’m grateful for the opportunity to do this research project and achieve a PhD degree. It has been a wonderful experience, allowing me to travel and contribute to science.’ Wright is currently a post-doctoral fellow in the HPP.

 

Thobakgale’s study investigated whether age at the time of HIV-1 infection, the viral proteins targeted by the immune system, the functionality of the generated responses, genetic make-up and the maternal immune responses to HIV, influenced disease progression in children.

 

Thobakgale found that slow progression to disease in a group of children can be attributed to genetic make-up, the acquisition of low fitness viruses from the mother or crippling of the virus by the child’s own immune responses. She also found that some infants had the ability to induce CD8+ T cell responses early in life. This information is encouraging for vaccine development.

 

Archary’s study was titled: Neutralizing Antibody Responses and Viral Evolution in a Longitudinal Cohort of HIV subtype C Infected Antiretroviral-naïve Individuals. Neutralizing antibodies (NAbs) typically play a key role in controlling viral infections and contribute to the protective effect of many successful vaccines, however, their role in HIV/AIDS disease progression remains unknown.

 

Archary profiled the ability of antibodies from people with slow disease against those with fast disease progression to inhibit the replication of diverse HIV-1 isolates.  She found that irrespective of disease progression status, antibodies from HIV infected people in Durban generally had a low range of viruses that they could neutralize with most of the responses biased towards local HIV-1 strains.  She also identified patterns of mutations in the HIV envelope glycoprotein.  This information may be useful for HIV vaccine design. 

 

Madlala examined genetic variation in cellular proteins required for HIV replication.  He found that genetic variation in these host proteins, particularly in the regulatory regions that impact expression levels of these proteins can affect susceptibility to HIV infection and viral control in those already affected.  These data lend support to ongoing efforts to develop a new class of antiretroviral drugs that can block the interaction of HIV proteins with cellular proteins as a way to disrupt the virus life cycle.

 

Ramduth’s study focused on CD4+ T cells, ‘helper’ cells that are required for effective antiviral immune responses.  She found that in HIV-1 infection, CD4+ T helper cells were almost always less frequent that their cytototoxic or killer counterparts, CD8+ T cells.  CD4+ T cell responses were mainly directed against the viral protein Gag, and the stronger the responses to Gag, the better the level of viral control in HIV infected individuals.  CD4 responses in children (who exhibit very poor viral control) were relatively rare.  This study suggests that it will be important to induce virus-specific CD4 T helper cells for an effective HIV vaccine.

   

                                                                                                                                                    - Go to UKZN for original article

by MaryAnn Francis