INFECTIOUS DISEASES / Virology
Research Interests
Host-pathogen interactions, oncogenic viruses, cancer biology
Description of Research
Our research primarily focuses on oncogenic viruses relevant in the Sub-Saharan African context, an area that is additionally burdened by an HIV/AIDS epidemic of massive proportions. We are particularly interested in host-pathogen interactions of Kaposi’s sarcoma herpesvirus (KSHV) and Human papillomavirus (HPV), both viruses being associated with AIDS-defining malignancies, with the long-term aim of developing novel preventative and diagnostic tools. Our research comprises both basic laboratory-based in vitro and in vivo studies as well as clinical studies involving national and international collaborations.
Supported by funding from various sources such as the EDCTP, the NRF, the MRC, CANSA and the PRF, we have discovered novel molecules modulating the early events during HPV infection, such as vimentin and surfactant protein A. Additionally, we have identified genetic variants of the KSHV entry receptor, EPHA2, in a South African HIV-infected patient cohort that were associated with susceptibility to KSHV infection and Kaposi’s sarcoma prevalence. Moreover, we recently found that elevated KSHV viral load in the blood was associated with mortality in critically ill HIV-infected patients with suspected but not microbiologically confirmed tuberculosis. These findings provide opportunities for a) targeting virus entry to prevent cancers with KSHV or HPV etiology; and b) for developing novel diagnostics/prognostics tools for virus-associated cancers relevant in high-burden HIV settings.
Based on our expertise in virology and in response to the recent Covid-19 outbreak, we have supported the Institute of Infectious Diseases and Molecular Medicine (IDM) at the University of Cape Town in setting up a diagnostic pipeline to ramp up national SARS-CoV2 testing capacities. Moreover, current research efforts focus on elucidating and targeting SARS-CoV2 entry mechanisms with the aim to develop cost-effective inhalant preventative means during seasonal coronavirus outbreaks.
The Group has also recently started several new research activities in response to the global COVID-19 pandemic.
Proposed genetic factors associated with KSHV infection and/or development of Kaposi’s Sarcoma (KS). KSHV infects endothelial cells and following lytic infection, establishes latency from which reactivation events can occur; KS develops from latently infected endothelial cells (grey box). Gene names in green text indicate an association with decreased risk; red text an association with increased risk.
*Various HLA haplotypes are either protective or increase risk of KS development as detailed in Blumenthal et al., 2020 (Reviews in Medical Virology). Figure created with BioRender.com
Recent Publications
Lesmes-Rodriguez LC, Lambarey H, Chetram A, Riou C, Wilkinson RJ, Joyimbana W, Jennings L, Orrell C, Jaramillo-Hernandez DA and Schäfer G (2023). Previous exposure to common coronavirus HCoV-NL63 is associated with reduced COVID-19 severity in patients from Cape Town, South Africa. Front Virol (3):1125448. doi: 10.3389/fviro.2023.1125448.
du Bruyn E, Stek C, Daroowala R, Said-Hartley Q, Hsiao M, Schäfer G, Goliath RT, Abrahams F, Jackson A, Wasserman S, Allwood BW, Davis AG, Lai RP, Coussens AK, Wilkinson KA, de Vries J, Tiffin N, Cerrone M, Ntusi NAB; HIATUS consortium; Riou C and Wilkinson RJ (2023). Effects of tuberculosis and/or HIV-1 infection on COVID-19 presentation and immune response in Africa. Nat Commun 14(1):188. doi: 10.1038/s41467-022-35689-1.
Lambarey H, Blumenthal MJ, Chetram A, Joyimbana W, Jennings L, Tincho MB, Burgers WA, Orrell C and Schäfer G (2022). SARS-CoV-2 Infection Is Associated with Uncontrolled HIV Viral Load in Non-Hospitalized HIV-Infected Patients from Gugulethu, South Africa. Viruses 14(6):1222. doi: 10.3390/v14061222.
Blumenthal MJ, Lambarey H, Chetram A, Riou C, Wilkinson RJ and Schäfer G (2022). Kaposi’s Sarcoma-Associated Herpesvirus, but Not Epstein-Barr Virus, Co-infection Associates With Coronavirus Disease 2019 Severity and Outcome in South African Patients. Front Microbiol 12:795555. doi: 10.3389/fmicb.2021.795555.
Riou C, Schäfer G, du Bruyn E, Goliath RT, Stek C, Mou H, Hung D, Wilkinson KA and Wilkinson RJ (2022). Rapid, simplified whole blood-based multiparameter assay to quantify and phenotype SARS-CoV-2-specific T-cells. Eur Respir J 59(1):2100285. doi: 10.1183/13993003.00285-2021.
Carse S, Lang D, Katz AA and Schäfer G (2021). Exogenous Vimentin Supplementation Transiently Affects Early Steps during HPV16 Pseudovirus Infection. Viruses 13(12):2471. doi: 10.3390/v13122471.
Blumenthal MJ, Cornejo Castro EM, Whitby D, Katz AA and Schäfer G (2021). Evidence for altered host genetic factors in KSHV infection and KSHV-related disease development. Rev Med Virol 31(2):e2160. doi: 10.1002/rmv.2160.
