Inbred rat strains mimic the disparate human response to rift valley fever virus infection

Abstract

Abstract Rift Valley fever virus (RFFV) has long been a major pathogen of domestic animals and humans in sub‐Saharan Africa. In the last 5 yr it has been recognized that this agent not only causes a self‐limited febrile illness in humans but may also lead to fatal hemorrhagic fever and encephalitis. In 1977 the disease invaded Egypt for the first time in recorded history, resulting in an extensive epizootic/epidemic and threatening additional spread into the Middle East. Because of this unprecedented geographical extension and the florid human disease associated with it, we have studied the pathogenicity of an Egyptian isolate (Zagazig Hospital 501) for laboratory animals. During the course of these studies, inbred rat strains were found to have three distinct patterns of response. Wistar‐Furth and Brown Norway rats were exquisitely susceptible to the virus and died with extensive hepatic necrosis 3 to 5 days after inoculation of only 5 plaque‐forming units (pfu). Lewis, Buffalo, DA, and Fischer 344 rats resisted subcutaneous infection with 5 × 10 5 pfu. ACI and Maxx rats were moderately susceptible to the lethal effects of 5 × 10 3 to 5 × 10 5 pfu of the virus and died within 2 to 3 wk with encephalitis. These findings suggest that the genetic susceptibility of the host is responsible for the markedly different evolution of RVF in the rats. The clinical and virologic events following rat inoculation resembled the course of benign, encephalitic, or fulminant human disease. The inbred rat model may be useful in defining the critical determinants of severe human RVF and suggests that more attention should be directed to host genetic factors.