INFECTIOUS DISEASES / Virology
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.
Blumenthal MJ, Cornejo Castro E, Whitby D, Katz AA, Schäfer G. Evidence for altered host genetic factors in KSHV infection and KSHV-related disease development. Rev Med Virol. 2020 (in press) doi:10.1002/rmv.2160
Ujma S, Carse S, Chetty A, Horsnell W, Clark H, Madsen J, Mackay RM, Watson A, Griffiths M, Katz AA, Schäfer G. Surfactant Protein A Impairs Genital HPV16 Pseudovirus Infection by Innate Immune Cell Activation in A Murine Model. Pathogens. 2019 Dec 6;8(4):288. doi: 10.3390/pathogens8040288. PMID: 31817644
Blumenthal MJ, Schutz C, Barr D, Locketz M, Marshall V, Whitby D, Katz AA, Uldrick T, Meintjes G, Schäfer G. The Contribution of Kaposi’s Sarcoma-Associated Herpesvirus to Mortality in Hospitalized Human Immunodeficiency Virus-Infected Patients Being Investigated for Tuberculosis in South Africa. J Infect Dis. 2019 Jul 31;220(5):841-851. doi: 10.1093/infdis/jiz180. PMID: 31004430
Blumenthal MJ, Schutz C, Meintjes G, Mohamed Z, Mendelson M, Ambler JM, Whitby D, Mackelprang RD, Carse S, Katz AA, Schäfer G. EPHA2 sequence variants are associated with susceptibility to Kaposi’s sarcoma-associated herpesvirus infection and Kaposi’s sarcoma prevalence in HIV-infected patients. Cancer Epidemiol. 2018 Oct;56:133-139. doi: 10.1016/j.canep.2018.08.005. Epub 2018 Aug 31. PMID: 30176543
Jacobs BA, Chetty A, Horsnell WGC, Schäfer G, Prince S, Smith KA. Hookworm exposure decreases human papillomavirus uptake and cervical cancer cell migration through systemic regulation of epithelial-mesenchymal transition marker expression. Sci Rep. 2018 Aug 1;8(1):11547. doi: 10.1038/s41598-018-30058-9. PMID: 30069018
Schäfer G, Graham LM, Lang DM, Blumenthal MJ, Bergant Marušič M, Katz AA. Vimentin Modulates Infectious Internalization of Human Papillomavirus 16 Pseudovirions. J Virol. 2017 Jul 27;91(16):e00307-17. doi: 10.1128/JVI.00307-17. Print 2017 Aug 15. PMID: 28566373