Ngo, Thuy Bao Tran

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博士(獣医学)山口大学Yamaguchi Universit

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学 位 論 文 要 旨氏名: Ngo Thuy Bao Tran題 目： Studies on zoonotic infection of novel tick-borne viruses in Japan（ 日本における新規マダニ媒介性ウイルスのヒトへの感染に関する研究）論文要旨：Tick-borne viruses are carried by ticks and cause severe diseases in human and animals, resulting in signif icant public health problem in the world. In Japan, three human pathogenic tick-borne viruses, tick-borne encephali tis virus (TBEV), severe fever with thrombocytopenia syndrome virus (SFTSV) and Yezo virus (YEZV) have been reported unti l  now. The f irst case of TBEV infection was diagnosed in the southern area of Hokkaido in 1993, and TBEV infection was also reported in domestic animals, l ivestock, and wild animals in Hokkaido. Since the f irst case of  infection, SFTSV has been reported from 23 provinces of Japan and 498 cases of  SFTS were reported unti l 2020. YEZV was first identif ied from two patients in Hokkaido who showed acute febri le i l lness with thrombocytopenia and leukopenia af ter tick bite in 2019 and 2020, and antibodies to YEZV were also found in wild deers and raccoons.In recent years, several novel tick-borne viruses have been isolated or detected in Japan as Tarumizu tick virus, genus Coltivirus, K abuto M ountain virus (KAM V), genus Uukuvirus, family Phenuivir idae, Oz virus, genus Thogotovirus, M ukawa virus, genus Phlebovirus, and Yamaguchi virus, genus Flavivirus. However, the informations on their pathogenesis and transmission cycle are sti l l  l imited. In this thesis, serosurveil lance of novel tick-borne viruses which were isolated in Japan in 2018, Oz virus and KAM V, were performed among mammalians including humans to understand the potential as zoonotic pathogens.For survei l lance of Oz virus, sera of 24 humans, 40 monkeys, 124 wild boars and 76 Sika deer in Yamaguchi prefecture were analyzed by VN test, resulting in positive ratio of 8.3%, 47.5%, 60.5% and 74%, respectively. An ELISA using an Oz virus-infected cel l  extract was established for the survei l lance of Oz virus infection among variousmammalians in Japan. The results were compared to those of the VN test to determine the correlation between the ELISA and the VN test, resulting the correlation coeff icient between established ELISA and VN test in monkeys, wild boars, and Sika deer were 0.9163, 0.8807, and 0.7569, respectively. Since the results from EL ISA and V N test are correlated signif icantly, the established ELISA was applied for the serosurveil lance of  Oz virus infection in various samples in Japan. The nationwide surveil lance of Oz virus infection indicated that Oz virus was distributed mainly in the southern and western parts of Japan, but not in the northern and eastern parts of Japan. In addition, two hunters were positive for antibodies against Oz virus, suggesting Oz virus might be a zoonotic pathogen.Serological surveil lance of K AM V infection among humans and wild mammalians including monkey, wild boar, Sika deer, bear and nutria in Yamaguchi prefecture was conducted by VN test and indirect immunofluorescence assay (IFA). Sera of 24 humans, 59 monkeys, 171 wild boars, 233 Sika deer, 7 bears, and 27 nutria in Yamaguchi prefecture were analyzed by VN test. The positive ratio of humans, monkeys, wild boars, and Sika deerwere 20.8 %, 3.4 %, 33.9 % and 4.7 %, respectively. No positive samples were detected in bears and nutria. Though VN test was less sensitive than IFA especiall y in monkey sera, al l  VN-positive sera were confirmed to be positive by IFA using infected cel ls. The correlation coeff icients between VN test and IFA in human, monkey, wild boar, and Sika deer sera were 0.5745, 0.7198, 0.9967 and 0.9525, respectively. Since several hunters were seropositive against KAM V, KAM V might be a potential tick-borne zoonotic pathogen. In addition, KAM V was detected  in a nymphal pool of Haemaphysalis formosensis ticks col lected f rom vegetation by flagging in Wakayama Prefecture. H. flava seems to be a vector tick for KAM V, but also H. formosensis tick might be considered a candidate vector. In conclusion, our resul ts showed that Oz virus and K abuto M ountain virus are circulating among wild mammalians and ticks in Japan and sometimes infected human, suggesting that these two viruses might be the tick-borne zoonotic viruses. Furtherinvestigation is required to clari fy whether Oz virus and K abuto M ountain virus can cause diseases in human.

日本における新規マダニ媒介性ウイルスのヒトへの感染に関する研究

http://petit.lib.yamaguchi-u.ac.jp/29052/files/166174

日本における新規マダニ媒介性ウイルスのヒトへの感染に関する研究

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