Rift Valley Fever Virus Infection in Golden Syrian Hamsters

Abstract

Rift Valley fever virus (RVFV) is a formidable pathogen that causes severe disease and abortion in a variety of livestock species and a range of disease in humans that includes hemorrhagic fever, fulminant hepatitis, encephalitis and blindness. The natural transmission cycle involves mosquito vectors, but exposure can also occur through contact with infected fluids and tissues. The lack of approved antiviral therapies and vaccines for human use underlies the importance of small animal models for proof-of-concept efficacy studies. Several mouse and rat models of RVFV infection have been well characterized and provide useful systems for the study of certain aspects of pathogenesis, as well as antiviral drug and vaccine development. However, certain host-directed therapeutics may not act on mouse or rat pathways. Here, we describe the natural history of disease in golden Syrian hamsters challenged subcutaneously with the pathogenic ZH501 strain of RVFV. Peracute disease resulted in rapid lethality within 2 to 3 days of RVFV challenge. High titer viremia and substantial viral loads were observed in most tissues examined; however, histopathology and immunostaining for RVFV antigen were largely restricted to the liver. Acute hepatocellular necrosis associated with a strong presence of viral antigen in the hepatocytes indicates that fulminant hepatitis is the likely cause of mortality. Further studies to assess the susceptibility and disease progression following respiratory route exposure are warranted. The use of the hamsters to model RVFV infection is suitable for early stage antiviral drug and vaccine development studies.

Pathogenesis of Rift Valley Fever Virus Aerosol Infection in STAT2 Knockout Hamsters

“…Consistent with previous work in animal models with the pathogenic ZH501 strain of RVFV [ 7 , 8 , 9 , 13 , 24 , 25 , 26 ], our study found that a variety of tissues are able to support RVFV MP-12 replication in the STAT2 KO hamsters, demonstrating the ability of the virus to cause systemic infection and lethal disease in this model. Notably, however, previous studies with BALB/c mice, Lewis rats, and rhesus macaques challenged with aerosolized RVFV found substantial levels of viremia [ 9 , 13 , 26 ], whereas we found that only two hamsters that were moribund at the time of sacrifice, had detectable low-level viremia.…”

Syrian Hamster as an Animal Model for the Study on Infectious Diseases

“…The infection of RVFV in Syrian hamsters has been well-described (91). The study results have assessed the susceptibility of Syrian hamsters to RVFV infection and shown that viral infection results in viremia, elevation of viral loads in liver, brain, and spleen tissues, observation of severe hepatocellular necrosis in the early stage of infection, and intense immunoreactivity of affected hepatocytes (27, 92, 93). Furthermore, using Syrian hamsters, Scharton et al proved that prophylactic Favipiravir (T-705) can effectively protect infected individuals against RVFV infection and reduce delayed-onset neurologic disease observed with ribavirin treatment (94).…”

Structural and functional similarities in bunyaviruses: Perspectives for pan‐bunya antivirals

“…An alternative rodent model are Golden Syrian hamsters, which are susceptible to RVFV and Hantaviruses. When devoid of functional STAT‐2, they are also highly susceptible to SFTSV, showing thrombocytopenia, typical marked systemic inflammation, and mortality …”