Dengue, West Nile, Ebola and Zika are just some of the numerous viruses which have come to global notoriety in the last decades. One common characteristic: They are all primarily spread by blood. “Oral or sexual transmission occurs very rarely, although the virus is present in body fluids, like saliva or semen”, explains Dr. Rüdiger Groß from the Institute of Molecular Virology, Ulm University Medical Center. Dr. Groß is the first author of a study just published in “Nature Microbiology”, investigating the reason for preferential spread of these viruses by insects and other bloodborne routes. While it was already known that small cell-membrane derived lipid-bubbles, so called extracellular-vesicles (EVs), play a role in blocking viral infections, the mechanism remained unclear. Now, a collaborative effort of scientists from Ulm, Marburg, Göttingen, Heidelberg, Berlin, Sweden, the UK and the USA revealed why these EVs prevent oral and sexual transmission.

The new study shows that a specific lipid molecule, phosphatidylserine, on the EVs blocks the interaction of several viral pathogens with their cellular receptor. “This new mechanism may explain why Zika- and Dengue viruses are transmitted by blood-sucking insects rather than sexual or oral transmission. Blood lacks phosphatidylserine-exposing vesicles” explains Prof. Janis Müller, senior author of the manuscript. To further validate their hypothesis the team also tested potential inhibitory effects of phosphatidylserine-exposing vesicles on other viruses which are known to spread through oral or sexual transmission, including HIV-1 and SARS-CoV-2. As expected, they did not detect an inhibitory activity against these viruses, which use distinct entry pathways for infection.

Dr. Groß summarized: “Zika and other mosquito-transmissible viruses, like Dengue commonly use phosphatidylserine receptors to bind cells, masquerading as apoptotic cell-derived debris to invade cells. EVs are similarly lipid-enveloped and expose phosphatidylserine – so they compete with viral particles for this entry pathway. Notably, EVs greatly outnumber viral particles, e.g. by up to 10,000-fold in seminal fluid.” For further information see the article and an accompanying commentary by Leonid Margolis discussing these exciting new findings.