Fukushi S

References (3)

Title : Acute Respiratory Infection in Human Dipeptidyl Peptidase 4-Transgenic Mice Infected with Middle East Respiratory Syndrome Coronavirus - Iwata-Yoshikawa_2019_J.Virol_93_
Author(s) : Iwata-Yoshikawa N , Okamura T , Shimizu Y , Kotani O , Sato H , Sekimukai H , Fukushi S , Suzuki T , Sato Y , Takeda M , Tashiro M , Hasegawa H , Nagata N
Ref : J Virol , 93 : , 2019
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) infection can manifest as a mild illness, acute respiratory distress, organ failure, or death. Several animal models have been established to study disease pathogenesis and to develop vaccines and therapeutic agents. Here, we developed transgenic (Tg) mice on a C57BL/6 background; these mice expressed human CD26/dipeptidyl peptidase 4 (hDPP4), a functional receptor for MERS-CoV, under the control of an endogenous hDPP4 promoter. We then characterized this mouse model of MERS-CoV. The expression profile of hDPP4 in these mice was almost equivalent to that in human tissues, including kidney and lung; however, hDPP4 was overexpressed in murine CD3-positive cells within peripheral blood and lymphoid tissues. Intranasal inoculation of young and adult Tg mice with MERS-CoV led to infection of the lower respiratory tract and pathological evidence of acute multifocal interstitial pneumonia within 7 days, with only transient loss of body weight. However, the immunopathology in young and adult Tg mice was different. On day 5 or 7 postinoculation, lungs of adult Tg mice contained higher levels of proinflammatory cytokines and chemokines associated with migration of macrophages. These results suggest that the immunopathology of MERS-CoV infection in the Tg mouse is age dependent. The mouse model described here will increase our understanding of disease pathogenesis and host mediators that protect against MERS-CoV infection.IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) infections are endemic in the Middle East and a threat to public health worldwide. Rodents are not susceptible to the virus because they do not express functional receptors; therefore, we generated a new animal model of MERS-CoV infection based on transgenic mice expressing human DPP4 (hDPP4). The pattern of hDPP4 expression in this model was similar to that in human tissues (except lymphoid tissue). In addition, MERS-CoV was limited to the respiratory tract. Here, we focused on host factors involved in immunopathology in MERS-CoV infection and clarified differences in antiviral immune responses between young and adult transgenic mice. This new small-animal model could contribute to more in-depth study of the pathology of MERS-CoV infection and aid development of suitable treatments.
ESTHER : Iwata-Yoshikawa_2019_J.Virol_93_
PubMedSearch : Iwata-Yoshikawa_2019_J.Virol_93_
PubMedID: 30626685

Title : Non Susceptibility of Neonatal and Adult Rats against the Middle East Respiratory Syndrome Coronavirus - Iwata-Yoshikawa_2016_Jpn.J.Infect.Dis_69_510
Author(s) : Iwata-Yoshikawa N , Fukushi S , Fukuma A , Suzuki T , Takeda M , Tashiro M , Hasegawa H , Nagata N
Ref : Jpn J Infect Dis , 69 :510 , 2016
Abstract : The present study examined the susceptibility of rats to the Middle East respiratory syndrome coronavirus (MERS-CoV) and determined whether this animal is a suitable model for MERS-CoV infection. Immunohistochemical analysis identified dipeptidyl peptidase 4 (DPP4), a known receptor for MERS-CoV on type I pneumocytes from infected rats. Whereas adult rats developed antibodies against MERS-CoV spike protein after intranasal inoculation, there was no evidence of viral replication in the lungs of adult, young, or neonatal rats after intranasal inoculation with MERS-CoV. In addition, human DPP4-expressing rat kidney fibroblasts, but not rat DPP4-expressing cells, were susceptible to MERS-CoV. Taken together, these results suggest that the rat is not a useful animal model for studying MERS-CoV infection.
ESTHER : Iwata-Yoshikawa_2016_Jpn.J.Infect.Dis_69_510
PubMedSearch : Iwata-Yoshikawa_2016_Jpn.J.Infect.Dis_69_510
PubMedID: 27000459

Title : Inability of rat DPP4 to allow MERS-CoV infection revealed by using a VSV pseudotype bearing truncated MERS-CoV spike protein - Fukuma_2015_Arch.Virol_160_2293
Author(s) : Fukuma A , Tani H , Taniguchi S , Shimojima M , Saijo M , Fukushi S
Ref : Arch Virol , 160 :2293 , 2015
Abstract : Middle East respiratory syndrome (MERS) coronavirus (Co-V) contains a single spike (S) protein, which binds to a receptor molecule, dipeptidyl peptidase 4 (DPP4; also known as CD26), and serves as a neutralizing antigen. Pseudotyped viruses are useful for measuring neutralization titers against highly infectious viruses as well as for studying their mechanism of entry. In this study, we constructed a series of cytoplasmic deletion mutants of MERS-CoV S and compared the efficiency with which they formed pseudotypes with vesicular stomatitis virus. A pseudotype bearing an S protein with the C-terminal 16 amino acids deleted (MERSpv-St16) reached a maximum titer that was approximately tenfold higher than that of a pseudotype bearing a non-truncated full-length S protein. Using MERSpv-St16, we demonstrated the inability of rat DPP4 to serve as a functional receptor for MERS-CoV, suggesting that rats are not susceptible to MERS-CoV infection. This study provides novel information that enhances our understanding of the host range of MERS-CoV.
ESTHER : Fukuma_2015_Arch.Virol_160_2293
PubMedSearch : Fukuma_2015_Arch.Virol_160_2293
PubMedID: 26138557