Our paper showing that the South American bunyavirus Oropouche uses Lrp1 for efficient cellular infection is now out in PNAS! This study was led by Maddy Schwarz and is part of our larger collaboration with WashU in St. Louis. Its very intriguing that Oropouche virus (Peribunyaviridae) and Rift Valley fever virus (Phenuiviridae) both use Lrp1 when they are distantly related and have virtually no homology in Gn. This suggest a shared structural motif for reliance on Lrp1. Lots more to come on this subject.
Figure 6 shows that co-infection of mice with OROV and the high-affinity Lrp1 binding protein mRAP can protect mice from lethal disease, illustrating the in vivo relevance of this interaction. The mutant mRAP protein can partially protect mice from OROV, whereas it was not able to protect mice at all from similar Rift Valley fever virus infection.
mRAPD3 protects mice from lethal OROV IC infection and significantly reduces infectious virus in the brain at 3 dpi. (A) Mice were infected with 100 PFU of OROV IC alone or in combination with either mRAPD3, mutant mRAPD3, or the control protein VP30. They were monitored for 15 d to determine percentage of survival in each group. (B) A subset of mice from each group was euthanized at 3 dpi to collect brain tissue, which was processed by viral plaque assay. (C) Immunofluorescent microscopy of brain tissues (cerebral cortex) from mice euthanized at 3 dpi (20×). Scale bars, 250 μm. Statistical significance was determined using a Mantel-Cox test for survival and two-way ANOVA for log-transformed data. Experiments were repeated four times. **P < 0.01; ***P < 0.001; ****P < 0.0001. No tx, No treatment; mut, mutant.
Congrats to Maddy! This paper came together in a relatively short period of time!