The L, M, and S segments of Rift Valley fever virus MP-12 vaccine independently contribute to a temperature-sensitive phenotype

Shoko Nishiyama, Nandadeva Lokugamage, Tetsuro Ikegami

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Rift Valley fever (RVF) is endemic to Africa, and the mosquito-borne disease is characterized by "abortion storms" in ruminants and by hemorrhagic fever, encephalitis, and blindness in humans. Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) has a tripartite negative-stranded RNA genome (L, M, and S segments). A live-attenuated vaccine for RVF, the MP-12 vaccine, is conditionally licensed for veterinary use in the United States. MP-12 is fully attenuated by the combination of the partially attenuated L, M, and S segments. Temperature sensitivity (ts) limits viral replication at a restrictive temperature and may be involved with viral attenuation. In this study, we aimed to characterize the ts mutations for MP-12. The MP-12 vaccine showed restricted replication at 38°C and replication shutoff(100-fold or greater reduction in virus titer compared to that at 37°C) at 39°C in Vero and MRC-5 cells. Using rZH501 reassortants with either the MP-12 L, M, or S segment, we found that all three segments encode a temperature-sensitive phenotype. However, the ts phenotype of the S segment was weaker than that of theMor L segment. We identified Gn-Y259H, Gc-R1182G, L-V172A, and L-M1244I as major ts mutations for MP-12. The ts mutations in the L segment decreased viral RNA synthesis, while those in theMsegment delayed progeny production from infected cells. We also found that a lack of NSs and/or 78kD/NSm protein expression minimally affected the ts phenotype. Our study revealed that MP-12 is a unique vaccine carrying ts mutations in the L, M, and S segments.

Original languageEnglish (US)
Pages (from-to)3735-3744
Number of pages10
JournalJournal of Virology
Volume90
Issue number7
DOIs
StatePublished - 2016

Fingerprint

Rift Valley fever virus
Vaccines
vaccines
Phenotype
phenotype
Temperature
temperature
Rift Valley Fever
Rift Valley fever
mutation
Mutation
live vaccines
Phlebovirus
Bunyaviridae
mosquito-borne diseases
RNA
Attenuated Vaccines
abortion (animals)
blindness
Viral RNA

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

The L, M, and S segments of Rift Valley fever virus MP-12 vaccine independently contribute to a temperature-sensitive phenotype. / Nishiyama, Shoko; Lokugamage, Nandadeva; Ikegami, Tetsuro.

In: Journal of Virology, Vol. 90, No. 7, 2016, p. 3735-3744.

Research output: Contribution to journalArticle

@article{bb648e90af114b579d4eb0a06a9ff062,
title = "The L, M, and S segments of Rift Valley fever virus MP-12 vaccine independently contribute to a temperature-sensitive phenotype",
abstract = "Rift Valley fever (RVF) is endemic to Africa, and the mosquito-borne disease is characterized by {"}abortion storms{"} in ruminants and by hemorrhagic fever, encephalitis, and blindness in humans. Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) has a tripartite negative-stranded RNA genome (L, M, and S segments). A live-attenuated vaccine for RVF, the MP-12 vaccine, is conditionally licensed for veterinary use in the United States. MP-12 is fully attenuated by the combination of the partially attenuated L, M, and S segments. Temperature sensitivity (ts) limits viral replication at a restrictive temperature and may be involved with viral attenuation. In this study, we aimed to characterize the ts mutations for MP-12. The MP-12 vaccine showed restricted replication at 38°C and replication shutoff(100-fold or greater reduction in virus titer compared to that at 37°C) at 39°C in Vero and MRC-5 cells. Using rZH501 reassortants with either the MP-12 L, M, or S segment, we found that all three segments encode a temperature-sensitive phenotype. However, the ts phenotype of the S segment was weaker than that of theMor L segment. We identified Gn-Y259H, Gc-R1182G, L-V172A, and L-M1244I as major ts mutations for MP-12. The ts mutations in the L segment decreased viral RNA synthesis, while those in theMsegment delayed progeny production from infected cells. We also found that a lack of NSs and/or 78kD/NSm protein expression minimally affected the ts phenotype. Our study revealed that MP-12 is a unique vaccine carrying ts mutations in the L, M, and S segments.",
author = "Shoko Nishiyama and Nandadeva Lokugamage and Tetsuro Ikegami",
year = "2016",
doi = "10.1128/JVI.02241-15",
language = "English (US)",
volume = "90",
pages = "3735--3744",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "7",

}

TY - JOUR

T1 - The L, M, and S segments of Rift Valley fever virus MP-12 vaccine independently contribute to a temperature-sensitive phenotype

AU - Nishiyama, Shoko

AU - Lokugamage, Nandadeva

AU - Ikegami, Tetsuro

PY - 2016

Y1 - 2016

N2 - Rift Valley fever (RVF) is endemic to Africa, and the mosquito-borne disease is characterized by "abortion storms" in ruminants and by hemorrhagic fever, encephalitis, and blindness in humans. Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) has a tripartite negative-stranded RNA genome (L, M, and S segments). A live-attenuated vaccine for RVF, the MP-12 vaccine, is conditionally licensed for veterinary use in the United States. MP-12 is fully attenuated by the combination of the partially attenuated L, M, and S segments. Temperature sensitivity (ts) limits viral replication at a restrictive temperature and may be involved with viral attenuation. In this study, we aimed to characterize the ts mutations for MP-12. The MP-12 vaccine showed restricted replication at 38°C and replication shutoff(100-fold or greater reduction in virus titer compared to that at 37°C) at 39°C in Vero and MRC-5 cells. Using rZH501 reassortants with either the MP-12 L, M, or S segment, we found that all three segments encode a temperature-sensitive phenotype. However, the ts phenotype of the S segment was weaker than that of theMor L segment. We identified Gn-Y259H, Gc-R1182G, L-V172A, and L-M1244I as major ts mutations for MP-12. The ts mutations in the L segment decreased viral RNA synthesis, while those in theMsegment delayed progeny production from infected cells. We also found that a lack of NSs and/or 78kD/NSm protein expression minimally affected the ts phenotype. Our study revealed that MP-12 is a unique vaccine carrying ts mutations in the L, M, and S segments.

AB - Rift Valley fever (RVF) is endemic to Africa, and the mosquito-borne disease is characterized by "abortion storms" in ruminants and by hemorrhagic fever, encephalitis, and blindness in humans. Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) has a tripartite negative-stranded RNA genome (L, M, and S segments). A live-attenuated vaccine for RVF, the MP-12 vaccine, is conditionally licensed for veterinary use in the United States. MP-12 is fully attenuated by the combination of the partially attenuated L, M, and S segments. Temperature sensitivity (ts) limits viral replication at a restrictive temperature and may be involved with viral attenuation. In this study, we aimed to characterize the ts mutations for MP-12. The MP-12 vaccine showed restricted replication at 38°C and replication shutoff(100-fold or greater reduction in virus titer compared to that at 37°C) at 39°C in Vero and MRC-5 cells. Using rZH501 reassortants with either the MP-12 L, M, or S segment, we found that all three segments encode a temperature-sensitive phenotype. However, the ts phenotype of the S segment was weaker than that of theMor L segment. We identified Gn-Y259H, Gc-R1182G, L-V172A, and L-M1244I as major ts mutations for MP-12. The ts mutations in the L segment decreased viral RNA synthesis, while those in theMsegment delayed progeny production from infected cells. We also found that a lack of NSs and/or 78kD/NSm protein expression minimally affected the ts phenotype. Our study revealed that MP-12 is a unique vaccine carrying ts mutations in the L, M, and S segments.

UR - http://www.scopus.com/inward/record.url?scp=84960969660&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84960969660&partnerID=8YFLogxK

U2 - 10.1128/JVI.02241-15

DO - 10.1128/JVI.02241-15

M3 - Article

VL - 90

SP - 3735

EP - 3744

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 7

ER -