Lrp1 is a host entry factor for Rift Valley fever virus.

Rift Valley fever virus (RVFV) is a zoonotic pathogen with pandemic potential. RVFV entry is mediated by the viral glycoprotein (Gn), but host entry factors remain poorly defined. Our genome-wide CRISPR screen identified low-density lipoprotein receptor-related protein 1 (mouse Lrp1/human LRP1), heat shock protein (Grp94), and receptor-associated protein (RAP) as critical host factors for RVFV infection.

Neutrophil and macrophage influx into the central nervous system are inflammatory components of lethal Rift Valley fever encephalitis in rats.

Rift Valley fever virus (RVFV) causes severe disease in livestock concurrent with zoonotic transmission to humans. A subset of people infected with RVFV develop encephalitis, and significant gaps remain in our knowledge of how RVFV causes pathology in the brain. We previously found that, in Lewis rats, subcutaneous inoculation with RVFV resulted in subclinical disease while inhalation of RVFV in a small particle aerosol caused fatal encephalitis.

Rift Valley fever virus induces fetal demise in Sprague-Dawley rats through direct placental infection.

Rift Valley fever virus (RVFV) infections in pregnant livestock cause high rates of fetal demise; miscarriage in pregnant women has also been associated with RVFV infection. To address how RVFV infection during pregnancy causes detrimental effects on the fetus, we developed a pregnant rodent model of RVFV infection. We found that pregnant rats were more susceptible to RVFV-induced death than their nonpregnant counterparts and that RVFV infection resulted in intrauterine fetal death and severe congenital abnormalities, even in pups from infected asymptomatic pregnant rats.

Vascular permeability in the brain is a late pathogenic event during Rift Valley fever virus encephalitis in rats.

Rift Valley fever virus (RVFV) is a zoonotic disease of livestock that causes several clinical outcomes in people including febrile disease, hemorrhagic fever, and/or encephalitis. After aerosol infection with RVFV, Lewis rats develop lethal encephalitic disease, and we use this as a model for studying disease mechanisms of RVFV infection in the brain. Permeability of the brain vasculature in relation to virus invasion and replication is not known.

Inflammatory Biomarkers Associated with Lethal Rift Valley Fever Encephalitis in the Lewis Rat Model.

Rift Valley fever (RVF) is an emerging viral disease that causes significant human and veterinary illness in Africa and the Arabian Peninsula. Encephalitis is one of the severe complications arising from RVF virus (RVFV) infection of people, and the pathogenesis of this form of RVF is completely unknown. We use a novel reproducible encephalitic disease model in rats to identify biomarkers of lethal infection.