Africans need to think about deadly connection
In 1872, Hungarian dermatologist Moritz Kaposi described an unusual skin cancer which would ultimately become known as Kaposi’s sarcoma, or KS for short. At the time, KS was only really known in specific populations, the uneven geographic distribution hinting at external factors impacting the course of the disease.
In the 1980s, as the HIV epidemic emerged, there was a sharp increase in the number of KS cases in previously low-incidence countries, suggesting that the external factor might be an infectious agent. In 1994, the husband and wife team of Patrick S Moore and Yuan Chang led the identification in KS samples of DNA sequences of a previously unidentified human herpesvirus, now known as the Kaposi’s sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8).
Most people do not think about the link between infection and cancer, particularly with respect to HIV, even though KS was among the first AIDS-associated illnesses to be identified. For those of us in Africa, there is a particular need to be aware of this connection. The rates of KSHV infection in certain parts of Africa, the Mediterranean and South America are naturally higher than elsewhere. Many people will be infected from early childhood, without any effects. This is because, while KSHV is necessary to cause KS, it is not sufficient by itself, and other factors are needed for the disease to manifest.
It was the unfortunate combination of the naturally high occurrence of KSHV infection in the population with the rampant spread of HIV infection that made KS the most common HIV-associated cancer in Africa. In South Africa, KS is in the top 10 of all cancers diagnosed, and is the fifth most common cancer in men, predominantly striking economically active individuals between the ages of 20 and 49. It, therefore, represents both a significant health and economic burden to our nation.
There has been some good news since the introduction of widespread access to antiretroviral therapy (ART). While AIDS-associated KS is aggressive and lacks targeted and effective treatments, ART has led to a decline in KS cases in South Africa since 2008. However, ART is not the complete solution to KS, as many patients with well-controlled HIV infection, including children, still develop progressive KS. Up to a third of KS patients suffer negative side-effects of ART, which can in some cases be fatal. It is clear more understanding of the biology of KSHV, and the factors that influence the development and treatment of KS, is still needed. To date, much of the work on KS and KSHV has been done outside of Africa, or by international scientists on our populations. It is time for African scientists to become more fully involved. A major challenge is that the model systems for working with KS and KSHV in the laboratory are technically challenging and, in some cases, completely lacking. My research group at Rhodes University is fortunate to be part of a new collaborative study with Leeds University and the University of KwaZulu-Natal, funded by grants totalling more than R4 million from the Royal Society UK Challenge-Led scheme, the Newton Advanced Fellowship scheme from the Royal Academy of Sciences UK, and the Poliovirus Research Foundation in SA. We will be working with the leading Whitehouse research group at Leeds University to understand KSHV biology, evaluate a new potential drug target, and train students to work with KSHV models. The project integrates the expertise of the Whitehouse group in KSHV biology with our expertise in understanding how cells respond to stress, which has been developed through the programme of the Department of Science and Technology/National Research Fund (DST/NRF) South African Research Chair in Molecular and Cellular Biology of the Eukaryotic Stress Response. The millions of cells in our body must work together, coordinating the numerous, complex, interconnected biochemical processes with ultimate precision in order for normal life to continue. Any changes in the environment, such as heat or lack of oxygen or chemicals, disrupt this delicate cellular equilibrium and plunge the cell into potentially lethal stress. We and others have worked to describe how the stress response is a pre-programmed genetic reply aimed at correcting imbalances and allowing the cell to survive. And just as we need this stress response system, so do many viruses. And it seems that KSHV is no exception, hijacking aspects of the host cell stress system to allow it to persist. Our project will apply the fundamental understanding of the human system we have developed over the years to determine if we can cripple KSHV by taking out the key components of the system upon which it depends. Through this, we hope to take the first step to find targets and inhibitors which can form the platform for future development of the safe, specific and effective KS antivirals that patients need. Adrienne Edkins is the DST/NRF South African Research Chair in Molecular and Cellular Biology of the Eukaryotic Stress Response and Associate Professor of Biochemistry at Rhodes University.