Tetsuro Ikegami, Ph.D.
||Field of Study
||Azabu University, Kanagawa, Japan
||University of Tokyo, Tokyo, Japan
The James W. McLaughlin postdoctoral fellowship. The University of Texas Medical Branch.
||Japanese Society of Veterinary Science
||Japanese Society for Virology
||American Society for Virology
||American Society for Microbiology
Rift Valley fever virus (RVFV), which belongs to family Bunyaviridae, genus Phlebovirus, circulates between mosquitoes and ruminants in sub-Saharan African countries, and causes abortion and fetal malformation in pregnant ewes or other ruminants. RVFV outbreaks have been reported in several African countries and Arabian Peninsula, and after temporal febrile period, human patients exhibited hemorrhagic fever, encephalitis or blindness caused by retinal vasculitis. Future introduction of RVFV into U.S. or other non-endemic countries is one of important public health concerns. The pathogenesis of Rift valley fever is less characterized, and there are no available RVFV vaccines for general public.
RVFV has tripartite negative-stranded genomic RNA named S, M and L-segments. S-segment encodes N and NSs protein in ambi-sense manner. M-segment encodes single M ORF, and produces NSm, 78kD, G1 and G2 proteins by utilizing several start codons and co-translational cleavage, whereas L-segment encodes RNA-dependent RNA polymerase. Among those 7 viral proteins, NSs and NSm are known to be nonstructural proteins, which are not incorporated into virions. N and L proteins are essential for viral RNA replication, whereas G1 and G2 are major envelope proteins. The functions of 78kD and NSm are less characterized. NSs is known to be a major virulence factor with multiple functions, and inhibits cellular general transcription by inhibiting transcription factor IIH, interferon-b gene induction and dsRNA-dependent protein kinase (PKR).
Formalin-inactivated RVFV vaccine has been developed previously, yet several booster shots are required to get sufficient protection against wild-type RVFV. Highly immunogenic vaccine is more suitable to prevent the spread of RVFV in case of RVFV introduction. MP-12, which is a candidate of live-attenuated vaccine, has been generated by serial 12 times passages of Egyptian wild-type isolate, ZH548 strain, in MRC-5 cells in the presence of chemical mutagen 5-fluorouracil. MP-12 is proven to be highly immunogenic in ruminants and human volunteers. MP-12 carries several mutations in M and L-segments, yet MP-12 NSs is still as functional as wild-type RVFV NSs.
Our lab uses a well-established reverse genetics system of RVFV MP-12, and currently studies on the immunological significance of MP-12 NSs as a vaccine, as well as the detailed mechanisms of RVFV NSs multifunctions. We are also exploring next generation human RVFV vaccine candidates and better countermeasures against RVFV
- Ikegami T, Shirota K, Une Y, Nomura Y, Wada Y, Goto K, Takakura A, Itoh T, Fujiwara K. 1999. Naturally occurring Tyzzer’s disease in a calf. Vet. Pathol. 36:253-5. (PMID: 10332834)
- Ikegami T, Shirota K, Goto K, Takakura A, Itoh T, Kawamura S, Une U, Nomura Y, Fujiwara K. 1999. Enterocolitis associated with dual infection by Clostridium piliforme and feline panleukopenia virus in three kittens. Vet. Pathol. 36:613-5.( PMID: 10568445)
- Niikura M, Ikegami T, Saijo M, Kurane I, Miranda ME, Morikawa S. 2001. Detection of Ebola viral antigen by enzyme-linked immunosorbent assay using a novel monoclonal antibody to nucleoprotein. J Clin Microbiol. 39:3267-71. (PMID: 11526161)
- Ikegami T, Calaor AB, Miranda ME, Niikura M, Saijo M, Kurane I, Yoshikawa Y, Morikawa S. 2001. Genome structure of Ebola virus subtype Reston: differences among Ebola subtypes. Arch. Virol. 146:2021-7. (PMID: 11722021)
- Miranda ME, Yoshikawa Y, Manalo DL, Calaor AB, Miranda NL, Cho F, Ikegami T, Ksiazek TG.. 2002. Chronological and spatial analysis of the 1996 Ebola Reston virus outbreak in a monkey breeding facility in the Philippines. Exp. Anim. 51:173-9. (PMID: 12012728)
- Ikegami T, Miranda MEG, Calaor AB, Manalo DL, Miranda NJ, Niikura M, Saijo M, Une Y, Nomura Y, Kurane I, Ksiazek TG, Yoshikawa Y, Morikawa S. 2002. Histopathology of cynomolgus macaques naturally infected with Ebola virus subtype Reston in the Philippine outbreak in 1996. Exp Anim. 51:447-55. (PMID: 12451705 )
- Saijo M, Qing T, Niikura M, Maeda A, Ikegami T, Prehaud C, Kurane I, Morikawa S. 2002. Recombinant nucleoprotein-based enzyme-linked immunosorbent assay for detection of immunoglobulin G antibodies to Crimean-Congo hemorrhagic fever virus. J Clin Microbiol. 40:1587-91. (PMID: 11980926)
- Ikegami T, Saijo M, Niikura M, Miranda ME, Calaor AB, Hernandez M, Manalo DL, Kurane I, Yoshikawa Y, Morikawa S. 2002. Development of an immunofluorescence method for the detection of antibodies to Ebola virus subtype Reston by the use of recombinant nucleoprotein-expressing HeLa cells. Microbiol Immunol. 46:633-8. (PMID: 12437031)
- Ikegami T, Saijo M, Niikura M, Miranda ME, Calaor AB, Hernandez M, Manalo DL, Kurane I, Yoshikawa Y, Morikawa S. 2003. Immunoglobulin G enzyme-linked immunosorbent assay using truncated nucleoproteins of Reston Ebola virus. Epidemiol Infect. 130:533-9. (PMID: 12825739)
- Ikegami T, Saijo M, Niikura M, Miranda ME, Calaor AB, Hernandez M, Acosta L, Manalo DL, Kurane I, Yoshikawa Y, Morikawa S. 2003. Antigen capture enzyme-linked immunosorbent assay for specific detection of Reston Ebola virus nucleoprotein. Clin Diagn Lab Immunol. 10:552-7. (PMID: 12853385)
- Niikura M, Ikegami T, Saijo M, Kurata T, Kurane I, Morikawa S. 2003. Analysis of linear B-cell epitopes of the nucleoprotein of ebola virus that distinguish Ebola virus subtypes. Clin Diagn Lab Immunol. 10:83-7. (PMID: 12522044)
- Ikegami T, Peters CJ, Makino S. 2005. Rift Valley fever virus nonstructural protein NSs promotes viral RNA replication and transcription in a minigenome system. J. Virol. 79: 5606-15. (PMID: 15827175)
- Ikegami T, Won S, Peters CJ, Makino S. 2005. Rift Valley fever virus NSs mRNA is transcribed from an incoming antiviral sense S RNA segment. J. Virol. 79: 12106-11. (PMID: 16140788)
- Ikegami T, Won S, Peters CJ, Makino S. 2006. Rescue of infectious Rift Valley fever virus entirely from cDNA, analysis of virus lacking NSs gene, and expression of a foreign gene. J. Virol. 80: 2933-40. (PMID: 16501102)
- Won S, Ikegami T, Peters CJ, Makino S. 2006. NSm and 78-kilodalton proteins of Rift Valley fever virus are nonessential for viral replication in cell culture. J. Virol. 80: 8274-8. (PMID: 16873285)
- Kamitani W, Narayanan K, Huang C, Lokugamage K, Ikegami T, Ito N, Kubo H, Makino S. 2006. Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression by promoting host mRNA degradation. Proc. Natl. Acad. Sci. U.S.A. 103: 12885-12890. (PMID: 16912115)
- Ikegami T, Won S, Peters CJ, Makino S. 2007. Characterization of Rift Valley fever virus transcriptional terminations. J.Virol. 81: 8421-38. (PMID: 17537856)
- Won S, Ikegami T, Peters CJ, Makino S. 2007. NSm protein of Rift Valley fever virus suppresses virus-induced apoptosis. J.Virol. 81: 13335-45 (PMID: 17913816).
- Ikegami T, Narayanan K, Won S, Kamitani W, Peters CJ, and Makino S. 2009. Rift Valley fever virus NSs protein promotes post-transcriptional downregulation of protein kinase PKR and inhibits eIF2a phosphorylation. PLoS Pathog 5: e1000287 (PMID: 19197350).
- Ikegami T, and Makino S. 2009. Rift Valley fever vaccines. Vaccine. In press.