Location: Arthropod-borne Animal Diseases ResearchTitle: Distinct virulence of Rift Valley fever virus strains from different genetic lineages in a mouse model
|IKEGAMI, TETSURO - University Of Texas Medical Branch|
|BALOGH, AARON - Kansas State University|
|NISHIYAMA, SHOKO - University Of Texas Medical Branch|
|LOKUGAMAGE, NANDADEVA - University Of Texas Medical Branch|
|SAITO, TAIS - University Of Texas Medical Branch|
|MORRILL, JOHN - University Of Texas Medical Branch|
|SHIVANNA, VINAY - Kansas State University|
|INDRAN, SABARISH - Kansas State University|
|ZHANG, LIHONG - University Of Texas Medical Branch|
|SMITH, JENNIFER - University Of Texas Medical Branch|
|PEREZ, DAVID - University Of Texas Medical Branch|
|JUELICH, TERRY - University Of Texas Medical Branch|
|MOROZOV, IGOR - Kansas State University|
|FRIEBERG, ALEXANDER - University Of Texas Medical Branch|
|RICHT, JEURGEN - Kansas State University|
Submitted to: PLOS Neglected Tropical Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/23/2017
Publication Date: 12/21/2017
Citation: Ikegami, T., Balogh, A., Nishiyama, S., Lokugamage, N., Saito, T., Morrill, J., Shivanna, V., Indran, S., Zhang, L., Smith, J., Perez, D., Juelich, T., Morozov, I., Wilson, W.C., Frieberg, A., Richt, J. 2017. Distinct virulence of Rift Valley fever virus strains from different genetic lineages in a mouse model . PLOS Neglected Tropical Diseases. Dec. 21, 2017: 1-17. https://doi.org/10.1371/journal.pone.0189250.
Interpretive Summary: Rift Valley fever (RVF) is a mosquito-borne zoonotic disease that presents substantial threat to human and public health. The causative virus has slowly evolved over time. This study examined the differences of pathogenicity of different genetic lineages in a mouse model. It also examined whether sera from attenuated vaccinate animals would be effective mitigation tools for these distinct genetic lineages. The results suggests that the vaccines should be effective against different genetic strains of the virus.
Technical Abstract: Rift Valley fever virus (RVFV) causes hemorrhagic disease and high rates of abortions in ruminants, and hemorrhagic fever, encephalitis, or blindness in humans. Viral transmission occurs via mosquito vectors in endemic areas, which necessitates regular vaccination of susceptible livestock animals. Although ZH501 strain has been used as a challenge strain for past vaccine efficacy studies, further characterization of other RVFV strains is important to optimize ruminant and nonhuman primate RVFV challenge models. This study aimed to characterize the virulence of wild-type RVFV strains belonging to different genetic lineages in outbred CD1 mice. Among mice subcutaneously infected with 1x103 PFU of wild-type ZH501, Kenya 9800523, Kenya 90058, Saudi Arabia 200010911, OS1, OS7, SA75, Entebbe, or SA51 strains, those infected with SA51, Entebbe, or OS7 strain showed rapid dissemination of virus in livers and peracute necrotic hepatitis at 2-3 dpi. Additionally, recombinant SA51 (rSA51) and Zinga (rZinga) strains were subsequently recovered by reverse genetics, and their virulence tested in CD1 mice. rSA51 but not rZinga reproduced peracute RVF disease in mice. This study showed that RVFV strains in different genetic lineages display distinct virulence in outbred mice. Importantly, since wild-type RVFV strains contain defective-interfering RNA or various genetic subpopulations during passage from original viral isolations, recombinant RVFV strains, rSA51 and rZinga, generated by reverse genetics will be better suitable for reproducible challenge studies for vaccine development. It is a concern whether animals vaccinated with a single RVFV strain can be protected against different RVFV challenge strains. This study showed that sera derived from sheep or cattle vaccinated with MP-12 or rMP12-'NSm21/384 successfully neutralized plaque formation of Kenya 199800523, rZinga, OS1, Entebbe, and SA51 strains, suggesting that the currently available MP-12 vaccine strain may be able to protect against heterologous RVFV strains.