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Project A2: Stefanie Heym, associated doctoral researcher (PhD)

Impact of breast milk on transmission of the human T-cell leukaemia virus type 1 (HTLV-1)

Breastfeeding is recommended by the World Health Organization for at least 6 months up to 2 years of age, and it is proven that breast milk protects against several diseases and viral infections. Intriguingly, few viruses are preferentially transmitted via breastfeeding including human T-cell leukaemia virus type 1 (HTLV-1). HTLV-1 is a highly oncogenic yet neglected retrovirus that causes incurable diseases like adult T-cell leukaemia (ATL) after lifelong viral persistence. Worldwide, at least 5-10 million people are HTLV-1-infected and most of them are unaware of their infection. Breast milk constitutes the major route of mother-to-child transmission of HTLV-1. Other cell-containing body fluids relevant for HTLV-1 infection are blood products and semen. The risk of mother-to-child transmission increases with the duration of breastfeeding, however, abstinence from breastfeeding is not an option in resource-limited settings or underrepresented areas or populations. Despite significant progress in understanding details of cell-to-cell transmission, not very much is known about the oral route of infection. The overarching goal of my PhD project is to uncover the impact of breast milk on HTLV-1 mother-to-child transmission. Therefore, different fractions of milk will first be tested for their impact on HTLV-1 transmission in a flow cytometry-based co-culture assay. Since components of the breast milk whey showed a high inhibitory effect on viral transmission, we seek to identify metabolites that block vertical transmission using a mass spectrometry-based metabolomic approach. Identified candidates will further be evaluated for their inhibitory potential and compared with commercially available human milk oligosaccharides (HMOs). HMOs have been postulated to have broad antiviral effects studied for a variety of viruses, including rotaviruses, noroviruses, influenza viruses, and human immunodeficiency viruses, and potential protective and therapeutic applications are discussed. Finally, we will test whether breast milk also affects HTLV-1 transmission via the oral route in tonsil and epithelial barrier model systems. In the future, the inhibitory metabolites identified in this project can hopefully be further optimized as a possible prevention strategy of oral transmission that might ultimately allow infants to benefit from breastfeeding while reducing the risk of HTLV-1 transmission.