Rift valley fever virus MP-12 vaccine encoding toscana virus NSs retains neuroinvasiveness in mice

Sabarish V. Indran, Olga A. Lihoradova, Inaia Phoenix, Nandadeva Lokugamage, Birte Kalveram, Jennifer A. Head, Bersabeh Tigabu, Jennifer K. Smith, Lihong Zhang, Terry L. Juelich, Bin Gong, Alexander Freiberg, Tetsuro Ikegami

Research output: Contribution to journalArticle

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Abstract

Rift Valley fever is a mosquito-borne zoonotic disease endemic to sub-Saharan Africa. Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) causes high rates of abortion and fetal malformation in pregnant ruminants, and haemorrhagic fever, neurological disorders or blindness in humans. The MP-12 strain is a highly efficacious and safe live-attenuated vaccine candidate for both humans and ruminants. However, MP-12 lacks a marker to differentiate infected from vaccinated animals. In this study, we originally aimed to characterize the efficacy of a recombinant RVFV MP-12 strain encoding Toscana virus (TOSV) NSs gene in place of MP-12 NSs (rMP12- TOSNSs). TOSV NSs promotes the degradation of dsRNA-dependent protein kinase (PKR) and inhibits interferon-b gene up-regulation without suppressing host general transcription. Unexpectedly, rMP12-TOSNSs increased death in vaccinated outbred mice and inbred BALB/c or C57BL/6 mice. Immunohistochemistry showed diffusely positive viral antigens in the thalamus, hypothalamus and brainstem, including the medulla. No viral antigens were detected in spleen or liver, which is similar to the antigen distribution of moribund mice infected with MP-12. These results suggest that rMP12-TOSNSs retains neuroinvasiveness in mice. Our findings demonstrate that rMP12-TOSNSs causes neuroinvasion without any hepatic disease and will be useful for studying the neuroinvasion mechanism of RVFV and TOSV.

Original languageEnglish (US)
Pages (from-to)1441-1450
Number of pages10
JournalJournal of General Virology
Volume94
Issue numberPART7
DOIs
StatePublished - Jul 1 2013

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Sandfly fever Naples virus
Rift Valley fever virus
Vaccines
Viral Antigens
Ruminants
Phlebovirus
Rift Valley Fever
Bunyaviridae
eIF-2 Kinase
Attenuated Vaccines
Induced Abortion
Africa South of the Sahara
Liver
Zoonoses
Blindness
Nervous System Diseases
Culicidae
Thalamus
Inbred C57BL Mouse
Interferons

ASJC Scopus subject areas

  • Virology

Cite this

Indran, S. V., Lihoradova, O. A., Phoenix, I., Lokugamage, N., Kalveram, B., Head, J. A., ... Ikegami, T. (2013). Rift valley fever virus MP-12 vaccine encoding toscana virus NSs retains neuroinvasiveness in mice. Journal of General Virology, 94(PART7), 1441-1450. https://doi.org/10.1099/vir.0.051250-0

Rift valley fever virus MP-12 vaccine encoding toscana virus NSs retains neuroinvasiveness in mice. / Indran, Sabarish V.; Lihoradova, Olga A.; Phoenix, Inaia; Lokugamage, Nandadeva; Kalveram, Birte; Head, Jennifer A.; Tigabu, Bersabeh; Smith, Jennifer K.; Zhang, Lihong; Juelich, Terry L.; Gong, Bin; Freiberg, Alexander; Ikegami, Tetsuro.

In: Journal of General Virology, Vol. 94, No. PART7, 01.07.2013, p. 1441-1450.

Research output: Contribution to journalArticle

Indran, SV, Lihoradova, OA, Phoenix, I, Lokugamage, N, Kalveram, B, Head, JA, Tigabu, B, Smith, JK, Zhang, L, Juelich, TL, Gong, B, Freiberg, A & Ikegami, T 2013, 'Rift valley fever virus MP-12 vaccine encoding toscana virus NSs retains neuroinvasiveness in mice', Journal of General Virology, vol. 94, no. PART7, pp. 1441-1450. https://doi.org/10.1099/vir.0.051250-0
Indran SV, Lihoradova OA, Phoenix I, Lokugamage N, Kalveram B, Head JA et al. Rift valley fever virus MP-12 vaccine encoding toscana virus NSs retains neuroinvasiveness in mice. Journal of General Virology. 2013 Jul 1;94(PART7):1441-1450. https://doi.org/10.1099/vir.0.051250-0
Indran, Sabarish V. ; Lihoradova, Olga A. ; Phoenix, Inaia ; Lokugamage, Nandadeva ; Kalveram, Birte ; Head, Jennifer A. ; Tigabu, Bersabeh ; Smith, Jennifer K. ; Zhang, Lihong ; Juelich, Terry L. ; Gong, Bin ; Freiberg, Alexander ; Ikegami, Tetsuro. / Rift valley fever virus MP-12 vaccine encoding toscana virus NSs retains neuroinvasiveness in mice. In: Journal of General Virology. 2013 ; Vol. 94, No. PART7. pp. 1441-1450.
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