The dominant-negative inhibition of double-stranded RNA-dependent protein kinase PKR increases the efficacy of Rift Valley fever virus MP-12 vaccine.

Journal of Virology
Olga LihoradovaTetsuro Ikegami

Abstract

Rift Valley fever virus (RVFV), belonging to the genus Phlebovirus, family Bunyaviridae, is endemic to sub-Saharan Africa and causes a high rate of abortion in ruminants and hemorrhagic fever, encephalitis, or blindness in humans. MP-12 is the only RVFV strain excluded from the select-agent rule and handled at a biosafety level 2 (BSL2) laboratory. MP-12 encodes a functional major virulence factor, the NSs protein, which contributes to its residual virulence in pregnant ewes. We found that 100% of mice subcutaneously vaccinated with recombinant MP-12 (rMP12)-murine PKRN167 (mPKRN167), which encodes a dominant-negative form of mouse double-stranded RNA (dsRNA)-dependent protein kinase (PKR) in place of NSs, were protected from wild-type (wt) RVFV challenge, while 72% of mice vaccinated with MP-12 were protected after challenge. rMP12-mPKRN167 induced alpha interferon (IFN-α) in sera, accumulated RVFV antigens in dendritic cells at the local draining lymph nodes, and developed high levels of neutralizing antibodies, while parental MP-12 induced neither IFN-α nor viral-antigen accumulation at the draining lymph node yet induced a high level of neutralizing antibodies. The present study suggests that the expression of a dominant-ne...Continue Reading

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Citations

Mar 22, 2014·PLoS Neglected Tropical Diseases·Shin MurakamiShinji Makino
Mar 13, 2013·Current Opinion in Virology·Adolfo García-Sastre, Ignacio Mena
Mar 22, 2013·The Journal of General Virology·Sabarish V IndranTetsuro Ikegami
May 30, 2015·Virus Research·Kaori TerasakiShinji Makino
Dec 20, 2012·Expert Review of Vaccines·Olga Lihoradova, Tetsuro Ikegami
Oct 7, 2020·EFSA Journal·Søren Saxmose NielsenGabriele Zancanaro

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