Old and New World arenaviruses can cause severe hemorrhagic fever in humans. There are currently no FDA approved vaccines or drugs to battle arenavirus infection. The mechanism of arenavirus-cell fusion mediated by the glycoprotein complex (GPC) is not well understood. Using single virus labeling and imaging tools to examine entry pathways and the fusion mechanism of arenaviruses, such as Lassa, LCMV and Junin viruses. Our data suggest that arenavirus fusion is uniquely preceded by a viral membrane permeabilization step (Figure 6 and Movie 5), which likely promotes subsequent uncoating of arenaviral core. We also discovered that the late endosome-resident lipid, BMP, specifically promotes late steps of arenavirus fusion. We are also working on defining the preferred sites of SARS-CoV-2 fusion in cells expressing or lacking the TMPRSS2 protease and the impact of IFITM expression using single pseudovirus tracking in living cells.
