Two manuscripts in press:
Walters, A.W., M.R. Kujawa, J.R. Albe, W.B. Klimstra, and A.L. Hartman. Vascular permeability in the brain is a late pathogenic event during Rift Valley fever virus encephalitis in rats. *In press at Virology (accepted 10/19/18)
ABSTRACT: 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. Here, we found that vascular permeability in the brain occurred late in the course of infection and corresponded temporally to expression of matrix metalloproteinase-9 (MMP-9). Virus replication was ongoing within the central nervous system for several days prior to detectable vascular leakage. Based on this study, vascular permeability was not required for entry of RVFV into the brain of rats. Prevention of vascular leakage late in infection may be an important component for prevention of lethal neurological disease in the rat model.
McMillen, C.M., N. Arora, D.A. Boyles, J.R. Albe, M.R. Kujawa, J.F. Bonadio, C.B. Coyne, and A.L. Hartman. Rift Valley fever virus induces fetal demise through direct placental infection. BioRxiv 383745. [Preprint]. August 2, 2018 [cited 9/22/18]. Available from: https://doi.org/10.1101/383745.
*currently in press at Science Advances (accepted 10/9/18)
ABSTRACT: Rift Valley fever virus (RVFV) infections in pregnant livestock cause high rates of fetal demise; miscarriage in pregnant women have 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 non-pregnant counterparts and that RVFV infection resulted in intrauterine fetal death and severe congenital abnormalities, even in pups from infected asymptomatic pregnant rats. Virus distribution in infected dams was widespread, with a previously unrecognized preference for infection, replication, and tissue damage in the placenta. In human mid-gestation placental tissue, RVFV directly infected placental chorionic villi, with replication detected in the outermost syncytial layer. Our work identifies direct placental infection by RVFV as a mechanism for vertical transmission. This is the first study to show vertical transmission with a lethal outcome in a species other than livestock. This study highlights the potential impact of a future epidemic of this emerging mosquito-borne virus.
New Review article available online 5/31/18: Read about the history of Rift Valley Fever
McMillen & Hartman: Antiviral Research