DEVELOPMENT OF HUMANIZED MOUSE MODEL FOR STUDYING MOTHER TO CHILD HTLV-1 TRANSMISSION AND PREVENTION WITH HTLV-1 ANTIBODY TREATMENT.
Author(s): ,
Takuo Mizukami
Affiliations:
Department of Safety Research on Blood and Biologicals,National Institute of Infectious Diseases,Tokyo,Japan
,
Kiyoko Nojima
Affiliations:
Department of Safety Research on Blood and Biologicals,National Institute of Infectious Diseases,Tokyo,Japan
,
Yuko Sato
Affiliations:
Department of Safety Research on Blood and Biologicals,National Institute of Infectious Diseases,Tokyo,Japan
,
Keiko Furuhata
Affiliations:
Department of Safety Research on Blood and Biologicals,National Institute of Infectious Diseases,Tokyo,Japan
,
Eita Sasaki
Affiliations:
Department of Safety Research on Blood and Biologicals,National Institute of Infectious Diseases,Tokyo,Japan
,
Sahoko Matsuoka
Affiliations:
Department of Safety Research on Blood and Biologicals,National Institute of Infectious Diseases,Tokyo,Japan
,
Kazu Okuma
Affiliations:
Department of Safety Research on Blood and Biologicals,National Institute of Infectious Diseases,Tokyo,Japan
,
Hiroyuki Moriuchi
Affiliations:
Department of Pediatrics, Graduate School of Biomedical Sciences,Nagasaki University,Nagasaki,Japan
,
Kaoru Uchimaru
Affiliations:
Department of Computational Biology and Medical Sciences,University of Tokyo,Tokyo,Japan
,
Hirofumi Akari
Affiliations:
Primate Research Institute,Kyoto University,Kyoto,Japan
,
Masahiro Satake
Affiliations:
Central Blood Institute, Blood Service Headquarters,Japanese Red Cross Society,Tokyo,Japan
Isao Hamaguchi
Affiliations:
Department of Safety Research on Blood and Biologicals,National Institute of Infectious Diseases,Tokyo,Japan
EHA Library. Mizukami T. Jun 15, 2019; 267490; S907
Dr. Takuo Mizukami
Dr. Takuo Mizukami
Contributions
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Abstract

Abstract: S907

Type: Oral Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 16:45 - 17:00

Location: Hall G104

Background
Human T-cell leukemia virus type 1 (HTLV-1) infects mature T cells and causes adult T-cell leukemia (ATL) and a chronic inflammatory central nervous system disease called HAM/TSP. HTLV-1 transmissions mainly occurred in children via the breast milk of HTLV-1+ carrier mothers. Thus, bottle-feeding or avoiding long term breastfeeding are recommended in the endemic areas of Japan and this resulted in a drastic decrease in new HTLV-1 infections. Previous studies have shown that approximately 3% of children born from HTLV-1+ carrier mothers were still infected even when they were exclusively bottle-fed. This suggested the possible involvement of alternative HTLV-1 transmission routes, such as placental or birth canal transmission.

Aims
Here, we attempted to develop new humanized mouse model of HTLV-1 mother to child (MTC) transmission for evaluating HTLV-1 antibody to prevent HTLV-1 MTC infection.

Methods
NOD/SCID/gammac (null) (NOG) pregnant mice were intraperitoneally injected with human PBMCs before being transplanted with a mitomycin C-treated HTLV-1-infected cell line (MT-2). To evaluate the importance of HTLV-1 infections via breastfeeding or before birth, we designed a study that switched HTLV-1-infected carrier mother (CM) mice with non-infected healthy mother (HM) mice. HTLV-1 infection was determined by the real-time PCR quantification of HTLV-1 DNA isolated from mouse liver, peripheral blood and breastmilk.

Results
Although no HTLV-1-infected T cells were detected in the peripheral blood of newborn mice at day 14, HTLV-1-infected cells were exclusively observed in the liver tissues via FACS and PCR. Furthermore, highly enriched HTLV-1+ cells were still detected in mouse breast milk 26 days after birth by PCR. These data suggest that there might be an enrichment system of HTLV-1 infectious cells in mouse breast tissue. We next performed the mother-pup pair switching study. After switching, CM mice were maintained with HM mice pups (potentially HTLV-1), and HM mice were maintained with CM mice pups (potentially HTLV-1+). This switching at birth resulted in 28% of the potentially HTLV-1 pups to become HTLV-1+, since they were breastfed by an HTLV-1+ mother. Similarly, 42% of the potentially HTLV-1+ pups were HTLV-1+ at 40 days after switching, as they were breastfed by an HTLV-1 mother. These results suggested that both breastfeeding and canal or placental transmissions presented equal risks with respect to HTLV-1 infections. We finally analyzed the HTLV-1 infectious status both in mouse embryo and placenta at E17.5 and found HTLV-1+ cells both in fetal liver (25%) and placenta (37%).

Conclusion
Together, these data suggest that during pregnancy, HTLV-1 cells invade the fetal tissues and might be a potential resource of HTLV-1 infection. We are now trying to assess the effect of HTLV-1 antibody for preventing MTC HTLV-1 infection.

Session topic: 31. Transfusion medicine

Keyword(s): HTLV-1, Infection

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