Virology – Emerging Viruses

INFECTIOUS DISEASES / Virology

Research Interests

Host-pathogen interactions, oncogenic viruses, cancer biology

Description of Research

The Group’s research centres around the infection dynamics of oncogenic viruses, particularly in high HIV-prevalence regions of Sub-Saharan Africa (SSA). Adopting a translational research approach and with the long-term aim to develop novel preventative and diagnostic tools, we are focusing on host-pathogen interactions of three major contributors to cancer in HIV-infected individuals who are at considerably higher risk of developing virus-associated malignancies: Kaposi’s sarcoma herpesvirus (KSHV), Epstein-Barr virus (EBV), and Human papillomavirus (HPV).

Due to the dysregulated nature of gammaherpesvirus (KSHV and EBV) infection, particularly in HIV co-infected individuals, the viruses often present with inflammatory symptoms which are frequently misdiagnosed as other prevalent infectious diseases. The group has provided strong clinical evidence linking blood KSHV viral load (VL) to adverse disease outcomes in critically ill South African HIV-infected patients presenting with suspected tuberculosis, and more recently, in hospitalised severely ill COVID-19 patients [1]. These studies were pivotal in establishing KSHV as a critical pathogen in the differential diagnosis of infectious diseases presenting with inflammation. The clinical significance of determining KSHV VL was also demonstrated in HIV-related KS patients, where we showed that those with extremely high blood KSHV VL had worse disease outcomes, potentially due to concurrent undiagnosed KSHV-associated conditions. We further demonstrated how repeated SARS-CoV-2 exposure led to KSHV reactivation in non-hospitalised, unvaccinated HIV-infected individuals [2], particularly in those with elevated EBV VL [3], potentially increasing their risk for developing post-pandemic KSHV/EBV-associated diseases. Intriguingly, while their HIV VL and CD4 count responded to antiretroviral therapy, selected patients displayed persistent and uncontrolled KSHV viremia and increasing inflammatory markers. In contrast, we demonstrated that immunocompetent HIV-negative paediatric patients displayed effective immunological control of their KSHV and/or EBV infections, even in the presence of inflammation as a potential trigger for lytic reactivation [4].This research underscores the need for gammaherpesvirus diagnostics in clinical HIV care to improve early diagnosis and management of gammaherpesvirus related diseases in high-risk populations.

Our work on HPV has focused on identifying novel molecules involved in the early stages of infection. We discovered vimentin as a novel cell-surface restriction factor against HPV infection [5], and found that surfactant protein A enhanced HPV immune recognition and clearance [6]. This research has laid the foundation for potential new HPV prophylactics, especially given the limited cross-protection provided by existing vaccines.

In summary, our research provides opportunities for a) developing novel diagnostics/prognostics tools for virus-associated cancers relevant in high-burden HIV settings; and b) targeting virus entry to prevent cancers with KSHV, EBV or HPV etiology. Ultimately, this work contributes to improving global health by tackling cancers caused by viruses in vulnerable populations.

Recent Publications