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. 2022 Jun 7;84(7):992–1000. doi: 10.1292/jvms.22-0237

Nationwide survey of hepatitis E virus infection among wildlife in Japan

Milagros Virhuez MENDOZA 1,2, Kenzo YONEMITSU 2, Keita ISHIJIMA 2, Yudai KURODA 2, Kango TATEMOTO 1,2, Yusuke INOUE 1,2, Hiroshi SHIMODA 1, Ryusei KUWATA 3, Ai TAKANO 1, Kazuo SUZUKI 4, Ken MAEDA 1,2,*
PMCID: PMC9353082  PMID: 35675975

Abstract

In Japan, hepatitis E virus (HEV) causes hepatitis in humans through the consumption of raw or undercooked meat, including game meat. In the present study, nationwide surveillance of HEV infection among a total of 5,557 wild animals, including 15 species, was conducted in Japan. The prevalence of anti-HEV antibodies in wild boar was 12.4%, with higher positive rates in big boars (over 50 kg, 18.4%) than in small individuals (less than 30 kg, 5.3%). Furthermore, HEV RNA was more frequently detected in piglets than in older boars. Interestingly, the detection of HEV among wildlife by ELISA and RT-PCR suggested that HEV infection in Sika deer was a very rare event, and that there was no HEV infection among wild animals except for wild boar, Sika deer and Japanese monkeys. In conclusion, wild boar, especially piglets, are at high risk of HEV infection, while other wild animals showed less risk or no risk of HEV transmission.

Keywords: hepatitis E virus, seroprevalence, Sika deer, wild animal, wild boar

Worldwide, hepatitis E virus (HEV) is the causative agent of acute viral hepatitis. HEV outbreaks have been described in developing countries, with mortality rates reaching 20–30% in pregnant women [38, 40]. In industrialized countries, zoonotic food-borne transmission due to the ingestion of infected animal meat is considered to be the main route of infection, but solid organ transplantation and blood transfusion routes have also been described [15, 60]. Although HEV infection is generally self-limited, it can cause chronic hepatitis in immunocompromised patients [15].

HEV is a non-enveloped, single stranded positive sense RNA virus with a genome length of approximately 7.2 kb, which encodes 3 opening reading frames (ORFs). HEV belongs to the family Hepeviridae with two assigned genera: Othohepevirus with four species (A to D) and Piscihepevirus with a single species [42, 54]. Until now, Othohepevirus A has been classified into 8 genotypes. Genotypes 1 and 2 are found exclusively in humans, genotypes 3 and 4 are zoonotic and have been reported from various mammals [7, 41, 63]. Genotypes 5 and 6 were detected in Japanese wild boar, while genotypes 7 and 8 were described in dromedary and bactrian camels, respectively [50, 66].

In Japan, HEV genotypes 3 and 4 are predominant in human and animal populations, and domestic pigs are the main reservoir [36]. Food-borne transmission from game meat was first reported by the consumption of Sika deer meat (Cervus nippon) in 2003 [61]. Since then, HEV infections in humans were mainly linked to the consumption of pork and wild boar meat and several epidemiological surveys suggested that wild boar are highly susceptible to HEV infection [21, 50, 55, 58]. Furthermore, the HEV genome and antibodies have been found in companion, feral and wild animals, showing that the other species are also exposed to HEV infection by unknown route(s) [14, 27, 32, 67].

Despite increasing reports of zoonotic transmission from game meat, the distribution, and characteristics of HEV strains circulating among wild animals, including wild boar and Sika deer populations have not been fully understood. In addition, the shedding of the virus in wild boar feces has been observed [51], indicating that cohabiting wild animals are at risk of HEV infection.

In this study, a nationwide survey was conducted in order to assess the risk of zoonotic HEV infection among wild animals as well as to characterize the genotypes of the HEV strains in Japan.

MATERIALS AND METHODS

Serum samples

A total of 5,557 serum samples were collected from wild boar (Sus scrofa), Sika deer (Cervus nippon), raccoons (Procyon lotor), mice (Apodemus speciosus, Apodemus argenteus and Myodes smithii), Japanese monkeys (Macaca fuscata), raccoon dogs (Nyctereutes procyonoides), Japanese badgers (Meles anakuma), mask palm civets (Paguma larvata), nutrias (Myocastor coypus), weasels (Mustela itatsi and Mustela sibirica), Japanese black bears (Ursus thibetanus), Japanese martens (Martes melampus), Japanese hares (Lepus brachyurus), red foxes (Vulpes vulpes) and Reeve’s muntjac (Muntiacus reevesi).

A total of 2,375 serum samples from wild boar were collected in Aomori (n=4), Chiba (n=91), Ehime (n=311), Gifu (n=144), Gunma (n=48), Hyogo (n=44), Kagawa (n=116), Kagoshima (n=5), Kumamoto (n=182), Oita (n=92), Okinawa (n=97), Tochigi (n=163), Toyama (n=183), Wakayama (n=457), and Yamaguchi (n=438) prefectures (Fig. 1). From Sika deer, 2,250 serum samples were collected from Aomori (n=39), Chiba (n=107), Ehime (n=45), Gifu (n=339), Gunma (n=106), Hokkaido (n=49), Kagawa (n=65), Kagoshima (n=29), Nagano (n=47), Oita (n=12), Wakayama (n=347), Yamaguchi (n=1,000) and Yamanashi (n=65) prefectures. In addition, 275, 160, 149, 115, 110, 36, 24, 22, 13, 13, 8, 6 and 1 serum samples were collected from raccoons, mice, monkeys, racoon dogs, badgers, mask palm civets, nutrias, weasels, bears, martens, hares, foxes and muntjac, respectively. The collection and location are described in Fig. 1 and Table 1. These wild animals were found dead (roadkill or unknown reasons) or were mainly captured as countermeasures under the official population control program. All collected serum samples were stored at −20°C until use. There was no overlap in examined animals between this study and our previous reports [13, 67].

Fig. 1.

Fig. 1.

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Geographic distribution of wild boar sampling areas in Japan. The number of anti-hepatitis E virus antibody-positive animals, the number of examined animals and percentage of positive animals are indicated by prefecture. The percentages are indicated by shading.

Table 1. Seroprevalence of hepatitis E virus (HEV) infection among wild animals in Japan.

Species Prefecture Year Percentage of positive animals
(Number of HEV-positive animals/
Number of examined animals)
Wild boar Aomori 2021 0% (0/4)
Chiba 2015–2019 49.5% (45/91)
Ehime 2016–2021 8.7% (27/311)
Gifu 2014–2018 5.6% (8/144)
Gunma 2015–2019 41.7% (20/48)
Hyogo 2015–2016 31.8% (14/44)
Kagawa 2016–2021 19.0% (22/116)
Kagoshima 2016 20.0% (1/5)
Kumamoto 2017–2018 3.3% (6/182)
Oita 2012–2019 18.5% (17/92)
Okinawa 2019–2020 0% (0/97)
Tochigi 2011–2012 6.7% (11/163)
Toyama 2014–2021 9.8% (18/183)
Wakayama 2015–2021 9.2% (42/457)
Yamaguchi 2016–2021 14.4% (63/438)
Deer Aomori 2019–2021 0% (0/39)
Chiba 2014–2020 0% (0/107)
Ehime 2016–2019 0% (0/45)
Gifu 2014–2021 0% (0/339)
Gunma 2015–2021 0% (0/106)
Hokkaido 2012 0% (0/49)
Kagawa 2016–2021 1.5% (1/65)
Kagoshima 2015–2017 0% (0/29)
Nagano 2015–2016 0% (0/47)
Oita 2008–2012 0% (0/12)
Wakayama 2020–2021 0% (0/347)
Yamaguchi 2010–2021 0% (0/1,000)
Yamanashi 2014–2015 0% (0/65)
Raccoon Gunma 2013–2014 0% (0/5)
Hyogo 2015–2016 0% (0/23)
Wakayama 2009–2015 0% (0/247)
Mouse Ehime 2016–2018 0% (0/63)
Yamaguchi 2015–2019 0% (0/97)
Monkey Fukuoka 2014–2016 6.3% (2/32)
Wakayama 2012–2017 0% (0/50)
Yamaguchi 2018–2019 0% (0/67)
Raccoon dog Gunma 2013–2014 0% (0/9)
Wakayama 2014–2015 0% (0/88)
Yamaguchi 2016–2019 0% (0/18)
Badger Kagoshima 2016–2017 0% (0/13)
Wakayama 2008–2020 0% (0/94)
Yamaguchi 2018 0% (0/3)
Masked palm civet Gunma 2013–2014 0% (0/3)
Kagoshima 2017 0% (0/1)
Wakayama 2012–2015 0% (0/32)
Nutria Yamaguchi 2015–2016 0% (0/24)
Weasel Wakayama 2007–2015 0% (0/21)
Yamaguchi 2018 0% (0/1)
Bear Akita 2017 0% (0/13)
Marten Wakayama 2008–2015 0% (0/13)
Hare Wakayama 2008–2019 0% (0/7)
Yamaguchi 2018 0% (0/1)
Fox Wakayama 2008 0% (0/2)
Yamaguchi 2017–2018 0% (0/4)
Muntjac Chiba 2015 0% (0/1)
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Detection of anti-HEV antibodies among animal sera

Anti-HEV antibodies in wild animal sera were detected using our established ELISA [67], with a minor modification. ELISA antigen was prepared from HEV capsid protein expressing cells by transfection with the expression plasmid [67]. Peroxidase Conjugated Purified Recomb® Protein AG (Thermo Fisher Scientific, Waltham, MA, USA) was added as a secondary antibody. Following three washes with PBS-T, 100 µl of substrate agent (ABTS Microwell Peroxidase Substrate, Sera Care Life Sciences, Milford, MA, USA) was added to each well and the plates were gently shaken for 30 min at room temperature. Finally, the enzymatic reaction was stopped by adding 100 µl per well of 1% sodium dodecyl sulfate and the absorbance at a wavelength of 405 nm was measured using a spectrophotometer (Bio-Rad, Hercules, CA, USA). According to our previous report, the cut-off value was set at 0.437 for wild boar sera. For the other mammals, the cut-off value was tentatively set at 0.500.

Detection of HEV RNA in wild animals

A total of 3,489 samples were screened for the presence of HEV genomes. RNA was extracted from 140 µl of each serum sample using the QIAamp Viral RNA Mini kit (QIAGEN, Hilden, Germany) in accordance with the manufacturer’s instructions. Nested reverse transcription (RT)-polymerase chain reaction (PCR) was performed for the detection of HEV RNA using OneStep RT-PCR Kit (QIAGEN) and KOD-Plus-NEO (Toyobo, Osaka, Japan) according to the kit protocols. Primers to detect ORF 2 gene of HEV genotypes 1, 3 and 4 [21] were used for HEV detection [27]. The 378 bp amplicon was purified using a QIAquick Gel Extraction Kit (QIAGEN) and the sequence was determined using BigDye Terminator v.3.1 technology (FASMAC, Atsugi, Japan). The obtained sequences were deposited in the DNA Data Bank of Japan (DDBJ accession number: LC706485-LC706506).

Sequence analysis of mitochondrial DNA from sera

DNA extraction was performed using 100 µl of deer serum samples that were found to be positive for HEV RNA or anti-HEV antibodies, using the DNeasy Blood & Tissue Kit (QIAGEN). To determine the host genome, we used a set of primers (Mammalian-1 and Mammalian-2) targeting the cytochrome b gene region of the mitochondrial DNA, as described previously [17].

Phylogenetic analysis

The phylogenetic analysis was performed by using the MEGA7 software program [20] based on the partial ORF2 sequences (338 bp) and the phylogenetic tree was generated by the neighbor-joining method based on 1,000 replicates, using the Kimura’s two-parameter model. Updated HEV subtype reference strains were included for comparison [54].

Statistical analysis

Pearson’s χ2 analysis was performed to evaluate the associations among HEV seroprevalence, HEV genome detection, and the variables of sex and body weight. P values of <0.05 were considered to be statistically significant.

RESULTS

Prevalence of anti-HEV antibodies among wild boar

Sera were obtained from 2,375 wild boar captured in 15 prefectures in Japan between 2012 and 2021 and were tested for the presence of anti-HEV antibodies (Fig. 1). The overall seroprevalence of anti-HEV antibodies in the wild boar population was 12.4% (294/2,375) and the prevalence by prefecture ranged from 0% to 49.5% (Table 1). The seroprevalence in wild boar of >50 kg in body weight (18.4%) was significantly higher in comparison to that among wild boars of <30 kg in body weight (5.3%) (P<0.001). No significant difference was observed between males (12.1%) and females (13.6%) (Table 2).

Table 2. Prevalence of anti-hepatitis E virus (HEV) antibodies in wild boar in Japan.

Sex
 Body weight (kg)
 Total
Male Female No record <30 30–50 >50 No record
No. of examined animals 1,151 1,027 197 637 772 538 428 2,375
No. of positive animals 139 140 15 34 115 99 46 294
Percentage of anti-HEV antibody-positive animals 12.1% 13.6% 7.6% 5.3% 14.9% 18.4% 10.7% 12.4%
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Prevalence of anti-HEV antibodies among Sika deer

Serum samples from 2,250 Sika deer captured in 13 prefectures between 2008 and 2021, were screened for antibodies against HEV. The total seroprevalence was 0.04% (1/2,250). The seropositive deer was captured in Kagawa Prefecture (1/65) and was negative for HEV RNA (Table 1). The anti-HEV antibody-positive serum was confirmed to have originated from deer by a sequence analysis of mitochondrial DNA in the serum.

Prevalence of anti-HEV antibodies in other wild animals

Sera of various wild animals collected between 2008 and 2020 were tested for the presence of anti-HEV antibodies. Two of 149 Japanese monkeys (1.4%) possessed anti-HEV antibodies and both were captured in Fukuoka Prefecture, resulting in a local prevalence of 6.3% (2/32). Sera collected from 275 raccoons, 160 mice, 115 raccoon dogs, 110 Japanese badgers, 36 mask palmed civets, 24 nutrias, 22 weasels, 13 Japanese black bears, 13 Japanese martens, 8 Japanese hares, 6 red foxes and 1 Reeve’s muntjac were negative for anti-HEV antibodies (Table 1).

HEV RNA detection in sera of wild boar, deer and other wild animals in Japan

HEV RNA was detected from 21 wild boar serum samples (1.2%). The prevalence in the different prefectures ranged from 0% to 5.5% (Table 3), and a significant difference was observed between males (1.8%) and females (0.6%) (P<0.05). In addition, the prevalence of HEV RNA in wild boars of <30 kg in body weight (2.2%) was significantly higher than that in wild boars of >50 kg in body weight (0%) (P<0.001) (Table 4).

Table 3. Detection of hepatitis E virus (HEV) genome in wild animals in Japan.

Species Prefecture Year Percentage of positive animals
(Number of HEV-positive animals/
Number of examined animals)
Wild boar Aomori 2021 0% (0/4)
Chiba 2015–2019 5.5% (5/91)
Ehime 2016–2019 0% (0/115)
Gifu 2014–2018 0% (0/140)
Gunma 2015–2019 2.1% (1/48)
Hyogo 2009–2011 2.6% (2/77)
Kagawa 2016–2021 0.9% (1/116)
Oita 2012–2019 2.9% (2/68)
Toyama 2014–2021 0% (0/183)
Wakayama 2020–2021 0% (0/354)
Yamaguchi 2012–2021 1.7% (10/582)
Deer Aomori 2019–2021 0% (0/39)
Chiba 2014–2020 0% (0/108)
Ehime 2016–2019 0% (0/45)
Gifu 2014–2021 0% (0/339)
Gunma 2015–2021 0% (0/106)
Kagawa 2016–2021 0% (0/65)
Yamaguchi 2010–2021 0.1% (1/986)
Bear Akita 2017 0% (0/12)
Raccoon dog Yamaguchi 2018–2019 0% (0/7)
Fox Yamaguchi 2018 0% (0/2)
Badger Yamaguchi 2018 0% (0/1)
Hare Wakayama 2019 0% (0/1)
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Table 4. Detection of hepatitis E virus (HEV) RNA in wild boar in Japan.

Sex
 Body weight (kg)
 Total
Male Female No record <30 30–50 >50 No record
No. of examined animals 873 826 79 460 614 519 185 1,778
No. of positive animals 16 5 0 10 8 0 3 21
Percentage of HEV RNA-positive animals 1.8% 0.6% 0.0% 2.2% 1.3% 0.0% 1.6% 1.2%
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The HEV genome prevalence among Sika deer was 0.06% (1/1,688). The HEV-positive deer was captured in Yamaguchi prefecture. This HEV-positive serum was confirmed to have originated from Sika deer by a sequence analysis of mitochondrial DNA.

HEV RNA was not detected in serum samples from 12 Japanese black bears, 7 racoon dogs, 2 red foxes, 1 Japanese badger and 1 Japanese hare.

Phylogenetic analysis of HEV

The phylogenetic analysis of the 338 bp amplicons showed that 9 strains of HEV in wild boar and 1 strain of HEV in Sika deer belonged to genotype 4, while 12 belonged to genotype 3 (Fig. 2, Table 5). The Sika deer strain formed one cluster together with the other wild boar strains collected in the same area, and the cluster was tentatively classified as cluster 4j (Fig. 2).

Fig. 2.

Fig. 2.

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Phylogenetic analyses based on the partial open reading frame (ORF) 2 sequences (338 bp). Hepatitis E viruses from 21 wild boars and one deer (bold) were compared to the reference strains proposed by Smith et al. [54] and the closest strains available in GenBank. The phylogenetic tree with 1,000 bootstrap replicates was generated by the neighbor-joining method. Reference sequences were labeled as “host/country/strain/year (GenBank accession number) subtype”.

Table 5. Information on the hepatitis E virus (HEV) strains detected in the sera of wild animals.

Species Prefecture Year Isolate Accession number HEV genotype Sex Body weight
(kg)
Wild boar Hyogo 2010 HEV/wb/Hyogo/W10178/10 LC706485 3b ♂ 32
Hyogo 2011 HEV/wb/Hyogo/W10192/11 LC706486 3b ♂ 16
Yamaguchi 2012 HEV/wb/Shimonoseki/10/12 LC706487 4j ♂ 41
Yamaguchi 2014 HEV/wb/Shimonoseki/174/14 LC706489 4j ♀ 10
Yamaguchi 2014 HEV/wb/Shimonoseki/176/14 LC706490 4j ♂ 10
Chiba 2015 HEV/wb/Chiba/116/15 LC706494 3b ♂ 50
Yamaguchi 2015 HEV/wb/Shimonoseki/265/15 LC706491 4j ♂ 27
Yamaguchi 2015 HEV/wb/Shimonoseki/267/15 LC706492 4j ♂ 23
Yamaguchi 2015 HEV/wb/Shimonoseki/276/15 LC706493 4j ♂ 16
Yamaguchi 2015 HEV/wb/Shimonoseki/90/15 LC706495 4j ♂ 25
Chiba 2016 HEV/wb/Chiba/132/16 LC706496 3b ♂ 30
Chiba 2016 HEV/wb/Chiba/237/16 LC706498 3b ♀ 35
Gunma 2016 HEV/wb/Gunma/202/16 LC706497 3a ♀ 15
Yamaguchi 2017 HEV/wb/Shimonoseki/52/17 LC706499 4j ♂ 40
Chiba 2018 HEV/wb/Chiba/479/18 LC706500 3b ♂ 26
Yamaguchi 2018 HEV/wb/Iwakuni/81/18 LC706501 3b ♂ 31
Chiba 2019 HEV/wb/Chiba/934/19 LC706502 3b ♂ 40
Oita 2019 HEV/wb/Oita/1206/19 LC706503 3b ♂ No record
Oita 2019 HEV/wb/Oita/1211/19 LC706504 3b ♀ No record
Kagawa 2020 HEV/wb/Kagawa/1289/20 LC706505 3k ♀ 10
Yamaguchi 2021 HEV/wb/Shimonoseki/77/21 LC706506 4j ♂ No record
Deer Yamaguchi 2013 HEV/deer/Shimonoseki/19/13 LC706488 4j ♀ 40
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DISCUSSION

In this study, the prevalence of HEV infection among wild mammals was compared, indicating that HEV mainly circulated among wild boar populations, while the other mammals showed less or no susceptibility to HEV infection.

In Japan, the prevalence of the anti-HEV antibody-positive wild boar was 12.4% (294/2,375). The prevalence of anti-HEV antibodies in the wild boar population ranged from 4.9% to 57.6% in Europe [1, 2, 6, 11, 18, 19, 43, 56, 68], and from 4.5% to 38.1% in Asian countries [8, 22, 46]. In Japan, HEV seropositivity rates among wild boar varied by prefecture, ranging from 4.5% to 42% [13, 29, 31, 46]. In this study, the prefectures of Chiba and Gunma, which are located in the Kanto region showed higher rates of seropositivity in comparison to other regions (Fig. 1). This HEV geographical distribution was similar to the one observed in human patients in Japan [36, 48, 60]. Nonetheless, wild boars have not been found in Hokkaido prefecture, which is a highly endemic area for HEV infection [47]. Therefore, the relationship between seropositivity in wild boar and the number of HEV patients remains unclear.

In this study, small wild boar (<30 kg) were infected with HEV, while heavy wild boar (>50 kg) possessed anti-HEV antibodies. These results indicated that small wild boar were infected with HEV and that big boar developed antibodies after recovering from HEV infection. The previous studies in wild boar also showed an association between body weight and the prevalence of anti-HEV antibodies or with HEV RNA detection [5, 33]. These results are similar to those in domestic pigs [28]. On the other hand, there was no significant difference in detection of anti-HEV antibody between male and female, similar to our previous reports [67]. However, HEV RNA was detected in male more than in female. In the previous reports, there was significant association between sex and HEV infection in human, but not in pigs and wild boar [10, 25, 30, 39, 52, 62]. Further study will be required to resolve this discordance in detection between HEV RNA and anti-HEV antibody.

In Sika deer, the seroprevalence was only 0.04% (1/2,250), which was consistent with previous reports showing a low prevalence of anti-HEV antibodies, ranging from 0% to 6.8% in Sika deer, roe deer (Capreolus capreolus), red deer (Cervus elaphus) and fallow deer (Dama dama) populations [1, 24, 34, 44, 59, 64, 65, 70]. We confirmed that this antibody-positive deer serum originated from a Sika deer by sequencing of mitochondrial DNA and reperforming the ELISA. In this study, the HEV gene was also detected in one Sika deer, indicating the risk of HEV infection by consumption of deer meat. Therefore, it seems likely that Sika deer can be infected with HEV, but that such events must be very rare. In addition, other studies reported higher HEV seroprevalence in moose (Alces alces), reindeer (Rangifer tarandus) and red deer, which showed seroprevalence rates of 9.1–19.5%, 12–23.1% and 10–12.85%, respectively [3, 4, 23, 45, 53]. The variation in seroprevalence among the family Cervidae may be influenced by animal behavior or cohabiting species.

Genotypes 3 and 4 are predominant in Asia [7, 41]. Moreover, subtypes 3a, 3b, 3e, 3f and 3k and subtypes 4c, 4d, 4f and 4i have been detected in humans, pigs, wild boar, and deer in Japan [35, 49, 54]. Our results showed that genotype 3 has a wide distribution among wild boar populations. Ten of our strains formed a cluster (subtype 3b) with Japan-indigenous strains from swine, rat, wild boar and human origin. One strain from Gunma Prefecture and one from Kagawa Prefecture were more closely related to subtypes 3a and 3k, respectively. The genotype 4 strains, detected from 9 wild boar and 1 Sika deer in Yamaguchi Prefecture, formed one cluster with previously reported strains of wild boar and a human zoonotic case in Yamaguchi prefecture [13, 37]. The continuous circulation of similar strains in this area since 2011 and the formation of a cluster distinct from previously reported genotype 4 subtypes, suggests the presence of an endemic subtype, which was tentatively named 4j.

Until now, only genotype 3 strains have been detected from deer [1, 12, 35, 57]. Two genotype 4 human cases linked to consumption of deer meat were reported in South Korea and Japan [9, 16], but HEV RNA in the meat was not analyzed. Therefore, this study is the first to report genotype 4 infection in deer.

Some wild animals have been shown to be susceptible to HEV infection [36, 63]. In this survey, we found seropositive rates of 1.4% (2/149) in Japanese monkeys, which was in consistent with previous reports in non-human primates that showed HEV circulation among macaques [14, 26, 69]. However, the other wild animals were negative for anti-HEV antibodies or HEV RNA. The primers used in this study could detect strains belonging to the Orthohepevirus A species, so we cannot deny the circulation of other species, like Orthohepevirus C. Overall, our findings, which were based on a nationwide survey of wild animals, indicated that the wild boar population is the dominant reservoir of HEV in Japan.

In conclusion, the wild boar population is the dominant reservoir for HEV infection in the field in Japan. In addition, young wild boars were more frequently infected with HEV, suggesting the risk of HEV infection from piglets. Sika deer were rarely infected with HEV, indicating that there is a low, but not zero, risk of HEV infection from Sika deer.

POTENTIAL CONFLICTS OF INTEREST

The authors have nothing to disclose.

Acknowledgments

Sampling of wild animal sera was performed by Dr. Tsutomu Takeda in Utsunomiya University, Dr. Masako Ando in Kagoshima University and Dr. Mayumi Yokoyama in University of Hyogo, many hunters in Yamaguchi and Wakayama prefectures, and the Japan Livestock Industry Association (Ehime, Kagawa, Gifu, Toyama, Chiba, Aomori). This research was funded by AMED Grant (JP20wm0225009, JP22fk0108634), and Health Labour Sciences Research Grant (21HA2006, 21KA1003, H30-shokuhin-ippan-004). MVM is supported by MEXT scholarship.

REFERENCES

  • 1.Anheyer-Behmenburg H. E., Szabo K., Schotte U., Binder A., Klein G., Johne R.2017. Hepatitis E virus in wild boars and spillover infection in red and roe deer, Germany, 2013–2015. Emerg. Infect. Dis. 23: 130–133. doi: 10.3201/eid2301.161169 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Barroso P., Risalde M. A., García-Bocanegra I., Acevedo P., Barasona J. Á., Caballero-Gómez J., Jiménez-Ruiz S., Rivero-Juárez A., Montoro V., Vicente J.2021. Long-term determinants of the seroprevalence of the hepatitis E virus in wild boar (Sus scrofa). Animals (Basel) 11: 1805. doi: 10.3390/ani11061805 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Bartolo I., Ponterio E., Angeloni G., Morandi F., Ostanello F., Nicoloso S., Ruggeri F. M.2017. Presence of hepatitis E virus in a RED deer (Cervus elaphus) population in central Italy. Transbound. Emerg. Dis. 64: 137–143. doi: 10.1111/tbed.12353 [DOI] [PubMed] [Google Scholar]
  • 4.Boadella M., Casas M., Martín M., Vicente J., Segalés J., de la Fuente J., Gortázar C.2010. Increasing contact with hepatitis E virus in red deer, Spain. Emerg. Infect. Dis. 16: 1994–1996. doi: 10.3201/eid1612.100557 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Burri C., Vial F., Ryser-Degiorgis M. P., Schwermer H., Darling K., Reist M., Wu N., Beerli O., Schöning J., Cavassini M., Waldvogel A.2014. Seroprevalence of hepatitis E virus in domestic pigs and wild boars in Switzerland. Zoonoses Public Health 61: 537–544. [DOI] [PubMed] [Google Scholar]
  • 6.Caruso C., Modesto P., Bertolini S., Peletto S., Acutis P. L., Dondo A., Robetto S., Mignone W., Orusa R., Ru G., Masoero L.2015. Serological and virological survey of hepatitis E virus in wild boar populations in northwestern Italy: detection of HEV subtypes 3e and 3f. Arch. Virol. 160: 153–160. doi: 10.1007/s00705-014-2246-5 [DOI] [PubMed] [Google Scholar]
  • 7.Casares-Jimenez M., Lopez-Lopez P., Caballero-Gomez J., Frias M., Perez-Hernando B., Oluremi A. S., Risalde M. A., Ruiz-Caceres I., Opaleye O. O., Garcia-Bocanegra I., Rivero-Juarez A., Rivero A.2021. Global molecular diversity of Hepatitis E virus in wild boar and domestic pig. One Health 13: 100304. doi: 10.1016/j.onehlt.2021.100304 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Choe S., Song S., Park G. N., Shin J., Kim K. S., Cha R. M., Hyun B. H., Park B. K., An D. J.2020. Detection of subtypes (3a, 4a and 4d) and high prevalence of hepatitis E virus in Korean wild boar. Vet. Microbiol. 240: 108531. doi: 10.1016/j.vetmic.2019.108531 [DOI] [PubMed] [Google Scholar]
  • 9.Choi J. Y., Lee J. M., Jo Y. W., Min H. J., Kim H. J., Jung W. T., Lee O. J., Yun H., Yoon Y. S.2013. Genotype-4 hepatitis E in a human after ingesting roe deer meat in South Korea. Clin. Mol. Hepatol. 19: 309–314. doi: 10.3350/cmh.2013.19.3.309 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Dalton H. R., Kamar N., Baylis S. A., Moradpour D., Wedemeyer H., Negro F., European Association for the Study of the Liver. Electronic address: easloffice@easloffice.euEuropean, Association for the Study of the Liver. 2018. EASL Clinical Practice Guidelines on hepatitis E virus infection. J. Hepatol. 68: 1256–1271. doi: 10.1016/j.jhep.2018.03.005 [DOI] [PubMed] [Google Scholar]
  • 11.de Deus N., Peralta B., Pina S., Allepuz A., Mateu E., Vidal D., Ruiz-Fons F., Martín M., Gortázar C., Segalés J.2008. Epidemiological study of hepatitis E virus infection in European wild boars (Sus scrofa) in Spain. Vet. Microbiol. 129: 163–170. doi: 10.1016/j.vetmic.2007.11.002 [DOI] [PubMed] [Google Scholar]
  • 12.Forgách P., Nowotny N., Erdélyi K., Boncz A., Zentai J., Szucs G., Reuter G., Bakonyi T.2010. Detection of hepatitis E virus in samples of animal origin collected in Hungary. Vet. Microbiol. 143: 106–116. doi: 10.1016/j.vetmic.2009.11.004 [DOI] [PubMed] [Google Scholar]
  • 13.Hara Y., Terada Y., Yonemitsu K., Shimoda H., Noguchi K., Suzuki K., Maeda K.2014. High prevalence of hepatitis E virus in wild boar (Sus scrofa) in Yamaguchi Prefecture, Japan. J. Wildl. Dis. 50: 378–383. doi: 10.7589/2013-06-144 [DOI] [PubMed] [Google Scholar]
  • 14.Hirano M., Ding X., Tran H. T. T., Li T. C., Takeda N., Sata T., Nakamura S., Abe K.2003. Prevalence of antibody against hepatitis E virus in various species of non-human primates: evidence of widespread infection in Japanese monkeys (Macaca fuscata). Jpn. J. Infect. Dis. 56: 8–11. [PubMed] [Google Scholar]
  • 15.Kamar N., Selves J., Mansuy J. M., Ouezzani L., Péron J. M., Guitard J., Cointault O., Esposito L., Abravanel F., Danjoux M., Durand D., Vinel J. P., Izopet J., Rostaing L.2008. Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N. Engl. J. Med. 358: 811–817. doi: 10.1056/NEJMoa0706992 [DOI] [PubMed] [Google Scholar]
  • 16.Kawamura K., Kobayashi Y., Takahashi K., Souda K., Sumiyoshi S., Kawata K., Takahashi Y., Makino S., Noritake H., Nakamura H., Abe N., Masahiro A.2010. Three cases of hepatitis E after eating deer meat or wild boar liver in West Shizuoka, Japan. Japan Soc. Hepatol. 51: 418–424. [Google Scholar]
  • 17.Kim K. S., Tsuda Y., Yamada A.2009. Bloodmeal identification and detection of avian malaria parasite from mosquitoes (Diptera: Culicidae) inhabiting coastal areas of Tokyo Bay, Japan. J. Med. Entomol. 46: 1230–1234. doi: 10.1603/033.046.0535 [DOI] [PubMed] [Google Scholar]
  • 18.Kozyra I., Jabłoński A., Bigoraj E., Rzeżutka A.2020. Wild boar as a sylvatic reservoir of hepatitis E virus in Poland: A cross-sectional population study. Viruses 12: 1–9. doi: 10.3390/v12101113 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Kukielka D., Rodriguez-Prieto V., Vicente J., Sánchez-Vizcaíno J. M.2016. Constant hepatitis E virus (HEV) circulation in wild boar and red deer in Spain: an increasing concern source of HEV zoonotic transmission. Transbound. Emerg. Dis. 63: e360–e368. doi: 10.1111/tbed.12311 [DOI] [PubMed] [Google Scholar]
  • 20.Kumar S., Stecher G., Tamura K.2016. MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol. Biol. Evol. 33: 1870–1874. doi: 10.1093/molbev/msw054 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Li T. C., Chijiwa K., Sera N., Ishibashi T., Etoh Y., Shinohara Y., Kurata Y., Ishida M., Sakamoto S., Takeda N., Miyamura T.2005. Hepatitis E virus transmission from wild boar meat. Emerg. Infect. Dis. 11: 1958–1960. doi: 10.3201/eid1112.051041 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Liang Q. L., Nie L. B., Zou Y., Hou J. L., Chen X. Q., Bai M. J., Gao Y. H., Hu G. X., Zhu X. Q.2019. Serological evidence of hepatitis E virus and influenza A virus infection in farmed wild boars in China. Acta Trop. 192: 87–90. doi: 10.1016/j.actatropica.2019.02.004 [DOI] [PubMed] [Google Scholar]
  • 23.Loikkanen E., Oristo S., Hämäläinen N., Jokelainen P., Kantala T., Sukura A., Maunula L.2020. Antibodies against hepatitis E virus (HEV) in European moose and white-tailed deer in Finland. Food Environ. Virol. 12: 333–341. doi: 10.1007/s12560-020-09442-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Matsuura Y., Suzuki M., Yoshimatsu K., Arikawa J., Takashima I., Yokoyama M., Igota H., Yamauchi K., Ishida S., Fukui D., Bando G., Kosuge M., Tsunemitsu H., Koshimoto C., Sakae K., Chikahira M., Ogawa S., Miyamura T., Takeda N., Li T. C.2007. Prevalence of antibody to hepatitis E virus among wild sika deer, Cervus nippon, in Japan. Arch. Virol. 152: 1375–1381. doi: 10.1007/s00705-007-0965-6 [DOI] [PubMed] [Google Scholar]
  • 25.Meester M., Tobias T. J., Bouwknegt M., Kusters N. E., Stegeman J. A., van der Poel W. H. M.2021. Infection dynamics and persistence of hepatitis E virus on pig farms - a review. Porcine Health Manag. 7: 16. doi: 10.1186/s40813-021-00189-z [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Melegari I., Di Profio F., Marsilio F., Sarchese V., Palombieri A., Friedrich K. G., Coccia F., Di Martino B.2018. Serological and molecular investigation for hepatitis E virus (HEV) in captive non-human primates, Italy. Virus Res. 251: 17–21. doi: 10.1016/j.virusres.2018.04.017 [DOI] [PubMed] [Google Scholar]
  • 27.Mendoza M. V., Yonemitsu K., Ishijima K., Minami S., Supriyono, Tran N. T. B., Kuroda Y., Tatemoto K., Inoue Y., Okada A., Shimoda H., Kuwata R., Takano A., Abe S., Okabe K., Ami Y., Zhang W., Li T. C., Maeda K.2021. Characterization of rabbit hepatitis E virus isolated from a feral rabbit. Vet. Microbiol. 263: 109275. [DOI] [PubMed] [Google Scholar]
  • 28.Meng X. J.2011. From barnyard to food table: the omnipresence of hepatitis E virus and risk for zoonotic infection and food safety. Virus Res. 161: 23–30. doi: 10.1016/j.virusres.2011.01.016 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Michitaka K., Takahashi K., Furukawa S., Inoue G., Hiasa Y., Horiike N., Onji M., Abe N., Mishiro S.2007. Prevalence of hepatitis E virus among wild boar in the Ehime area of western Japan. Hepatol. Res. 37: 214–220. doi: 10.1111/j.1872-034X.2007.00030.x [DOI] [PubMed] [Google Scholar]
  • 30.Modiyinji A. F., Sanding G. M. A. M., Atsama M. A., Monamele C. G., Nola M., Njouom R.2020. Serological and molecular investigation of hepatitis E virus in pigs reservoirs from Cameroon reveals elevated seroprevalence and presence of genotype 3. PLoS One 15: e0229073. doi: 10.1371/journal.pone.0229073 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Motoya T., Umezawa M., Goto K., Doi I., Nagata N., Ikeda Y., Sakuta A., Sasaki N., Ishii K.2019. High prevalence of hepatitis E virus infection among domestic pigs in Ibaraki Prefecture, Japan. BMC Vet. Res. 15: 87. doi: 10.1186/s12917-019-1816-x [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Nakamura M., Takahashi K., Taira K., Taira M., Ohno A., Sakugawa H., Arai M., Mishiro S.2006. Hepatitis E virus infection in wild mongooses of Okinawa, Japan: Demonstration of anti-HEV antibodies and a full-genome nucleotide sequence. Hepatol. Res. 34: 137–140. doi: 10.1016/j.hepres.2005.10.010 [DOI] [PubMed] [Google Scholar]
  • 33.Nakane K., Ito H., Isogai K., Itakura Y., Kasuya K., Kobayashi S.2015. Molecular investigation on the presence of hepatitis E virus in wild game in Okazaki City, Japan between April 2010 and November 2014. Shokuhin Eiseigaku Zasshi 56: 252–255 (in Japanese). doi: 10.3358/shokueishi.56.252 [DOI] [PubMed] [Google Scholar]
  • 34.Neumann S., Hackl S. S., Piepenschneider M., Vina-Rodriguez A., Dremsek P., Ulrich R. G., Groschup M. H., Eiden M.2016. Serologic and molecular survey of hepatitis E virus in German deer populations. J. Wildl. Dis. 52: 106–113. doi: 10.7589/2014-12-282 [DOI] [PubMed] [Google Scholar]
  • 35.Okamoto H.2007. Genetic variability and evolution of hepatitis E virus. Virus Res. 127: 216–228. doi: 10.1016/j.virusres.2007.02.002 [DOI] [PubMed] [Google Scholar]
  • 36.Okamoto H., Takahashi M., Nishizawa T.2003. Features of hepatitis E virus infection in Japan. Intern. Med. 42: 1065–1071. doi: 10.2169/internalmedicine.42.1065 [DOI] [PubMed] [Google Scholar]
  • 37.Okita K., Takahashi K., Harada K., Yukari T., Atsuyoshi H., Teruaki K., Akira K., Satoyoshi Y., Masahiro A., Kiwamu O.2012. A case of acute hepatitis E (genotype 4) after eating uncooked meat and liver of wild boar captured in Yamaguchi prefecture, with a viral genome relatively closer to a Chinese isolate than to Japanese strains. Japan Soc. Hepatol. 53: 534–537. [Google Scholar]
  • 38.Patra S.2007. Maternal and fetal outcomes in pregnant women with acute. Ann. Intern. Med. 147: 28–33. doi: 10.7326/0003-4819-147-1-200707030-00005 [DOI] [PubMed] [Google Scholar]
  • 39.Pavio N., Doceul V., Bagdassarian E., Johne R.2017. Recent knowledge on hepatitis E virus in Suidae reservoirs and transmission routes to human. Vet. Res. (Faisalabad) 48: 78. doi: 10.1186/s13567-017-0483-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Pérez-Gracia M. T., Suay-García B., Mateos-Lindemann M. L.2017. Hepatitis E and pregnancy: current state. Rev. Med. Virol. 27: e1929. doi: 10.1002/rmv.1929 [DOI] [PubMed] [Google Scholar]
  • 41.Primadharsini P. P., Nagashima S., Okamoto H.2019. Genetic variability and evolution of hepatitis e virus. Viruses 11: 456. doi: 10.3390/v11050456 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Purdy M. A., Harrison T. J., Jameel S., Meng X. J., Okamoto H., Van der Poel W. H. M., Smith D. B., Ictv Report Consortium. 2017. ICTV virus taxonomy profile: Hepeviridae. J. Gen. Virol. 98: 2645–2646. doi: 10.1099/jgv.0.000940 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Roth A., Lin J., Magnius L., Karlsson M., Belák S., Widén F., Norder H.2016. Markers for ongoing or previous hepatitis E virus infection are as common in wild ungulates as in humans in Sweden. Viruses 8: 1–12. doi: 10.3390/v8090259 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Rutjes S. A., Lodder-Verschoor F., Lodder W. J., van der Giessen J., Reesink H., Bouwknegt M., de Roda Husman A. M.2010. Seroprevalence and molecular detection of hepatitis E virus in wild boar and red deer in The Netherlands. J. Virol. Methods 168: 197–206. doi: 10.1016/j.jviromet.2010.05.014 [DOI] [PubMed] [Google Scholar]
  • 45.Sacristán C., Madslien K., Sacristán I., Klevar S., Neves C. G.2021. Seroprevalence of hepatitis E virus in moose (Alces alces), reindeer (Rangifer tarandus), red deer (Cervus elaphus), roe deer (Capreolus capreolus), and muskoxen (Ovibos moschatus) from Norway. Viruses. 13: 224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Sakano C., Morita Y., Shiono M., Yokota Y., Mokudai T., Sato-Motoi Y., Noda A., Nobusawa T., Sakaniwa H., Nagai A., Kabeya H., Maruyama S., Yamamoto S., Sato H., Kimura H.2009. Prevalence of hepatitis E virus (HEV) infection in wild boars (Sus scrofa leucomystax) and pigs in Gunma Prefecture, Japan. J. Vet. Med. Sci. 71: 21–25. doi: 10.1292/jvms.71.21 [DOI] [PubMed] [Google Scholar]
  • 47.Sakata H., Matsubayashi K., Iida J., Nakauchi K., Kishimoto S., Sato S., Ikuta K., Satake M., Kino S.2021. Trends in hepatitis E virus infection: analyses of the long-term screening of blood donors in Hokkaido, Japan, 2005–2019. Transfusion 61: 3390–3401. doi: 10.1111/trf.16700 [DOI] [PubMed] [Google Scholar]
  • 48.Sakata H., Matsubayashi K., Takeda H., Sato S., Kato T., Hino S., Tadokoro K., Ikeda H.2008. A nationwide survey for hepatitis E virus prevalence in Japanese blood donors with elevated alanine aminotransferase. Transfusion 48: 2568–2576. doi: 10.1111/j.1537-2995.2008.01910.x [DOI] [PubMed] [Google Scholar]
  • 49.Sato N., Watanabe S., Miura K., Morimoto N., Takaoka Y., Nomoto H., Isoda N., Nagashima S., Takahashi M., Okamoto H., Yamamoto H.2020. Clinical and virologic features of hepatitis E virus infection at a university hospital in Japan between 2000 and 2019. J. Med. Virol. 92: 3572–3583. doi: 10.1002/jmv.26248 [DOI] [PubMed] [Google Scholar]
  • 50.Sato Y., Sato H., Naka K., Furuya S., Tsukiji H., Kitagawa K., Sonoda Y., Usui T., Sakamoto H., Yoshino S., Shimizu Y., Takahashi M., Nagashima S., Jirintai, Nishizawa T., Okamoto H.2011. A nationwide survey of hepatitis E virus (HEV) infection in wild boars in Japan: identification of boar HEV strains of genotypes 3 and 4 and unrecognized genotypes. Arch. Virol. 156: 1345–1358. doi: 10.1007/s00705-011-0988-x [DOI] [PubMed] [Google Scholar]
  • 51.Schlosser J., Vina-Rodriguez A., Fast C., Groschup M. H., Eiden M.2015. Chronically infected wild boar can transmit genotype 3 hepatitis E virus to domestic pigs. Vet. Microbiol. 180: 15–21. doi: 10.1016/j.vetmic.2015.08.022 [DOI] [PubMed] [Google Scholar]
  • 52.Schotte U., Martin A., Brogden S., Schilling-Loeffler K., Schemmerer M., Anheyer-Behmenburg H. E., Szabo K., Müller-Graf C., Wenzel J. J., Kehrenberg C., Binder A., Klein G., Johne R.2022. Phylogeny and spatiotemporal dynamics of hepatitis E virus infections in wild boar and deer from six areas of Germany during 2013–2017. Transbound. Emerg. Dis. (in press). [DOI] [PubMed] [Google Scholar]
  • 53.Slukinova O. S., Kyuregyan K. K., Karlsen A. A., Potemkin I. A., Kichatova V. S., Semenov S. I., Stepanov K. M., Rumyantseva T. D., Mikhailov M. I.2021. Serological evidence of hepatitis E virus circulation among reindeer and reindeer herders. Vector Borne Zoonotic Dis. 21: 546–551. doi: 10.1089/vbz.2020.2727 [DOI] [PubMed] [Google Scholar]
  • 54.Smith D. B., Izopet J., Nicot F., Simmonds P., Jameel S., Meng X. J., Norder H., Okamoto H., van der Poel W. H. M., Reuter G., Purdy M. A.2020. Update: proposed reference sequences for subtypes of hepatitis E virus (species Orthohepevirus A). J. Gen. Virol. 101: 692–698. doi: 10.1099/jgv.0.001435 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55.Sonoda H., Abe M., Sugimoto T., Sato Y., Bando M., Fukui E., Mizuo H., Takahashi M., Nishizawa T., Okamoto H.2004. Prevalence of hepatitis E virus (HEV) infection in wild boars and deer and genetic identification of a genotype 3 HEV from a boar in Japan. J. Clin. Microbiol. 42: 5371–5374. doi: 10.1128/JCM.42.11.5371-5374.2004 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Spancerniene U., Buitkuviene J., Grigas J., Pampariene I., Salomskas A., Cepuliene R., Zymantiene J., Stankevicius A.2016. Seroprevalence of hepatitis E virus in lithuanian domestic pigs and wildlife. Acta Vet. Brno 85: 319–327. doi: 10.2754/avb201685040319 [DOI] [Google Scholar]
  • 57.Spancerniene U., Grigas J., Buitkuviene J., Zymantiene J., Juozaitiene V., Stankeviciute M., Razukevicius D., Zienius D., Stankevicius A.2018. Prevalence and phylogenetic analysis of hepatitis E virus in pigs, wild boars, roe deer, red deer and moose in Lithuania. Acta Vet. Scand. 60: 13. doi: 10.1186/s13028-018-0367-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Takahashi K., Kitajima N., Abe N., Mishiro S.2004. Complete or near-complete nucleotide sequences of hepatitis E virus genome recovered from a wild boar, a deer, and four patients who ate the deer. Virology 330: 501–505. doi: 10.1016/j.virol.2004.10.006 [DOI] [PubMed] [Google Scholar]
  • 59.Takahashi M., Nishizono A., Kawakami M., Fukui E., Isogai E., Matsuoka H., Yamamoto S., Mizuo H., Nagashima S., Murata K., Okamoto H.2022. Identification of hepatitis E virus in wild sika deer in Japan. Virus Res. 308: 198645. doi: 10.1016/j.virusres.2021.198645 [DOI] [PubMed] [Google Scholar]
  • 60.Takeda H., Matsubayashi K., Sakata H., Sato S., Kato T., Hino S., Tadokoro K., Ikeda H.2010. A nationwide survey for prevalence of hepatitis E virus antibody in qualified blood donors in Japan. Vox Sang. 99: 307–313. doi: 10.1111/j.1423-0410.2010.01362.x [DOI] [PubMed] [Google Scholar]
  • 61.Tei S., Kitajima N., Takahashi K., Mishiro S.2003. Zoonotic transmission of hepatitis E virus from deer to human beings. Lancet 362: 371–373. doi: 10.1016/S0140-6736(03)14025-1 [DOI] [PubMed] [Google Scholar]
  • 62.Temmam S., Besnard L., Andriamandimby S. F., Foray C., Rasamoelina-Andriamanivo H., Héraud J. M., Cardinale E., Dellagi K., Pavio N., Pascalis H., Porphyre V.2013. High prevalence of hepatitis E in humans and pigs and evidence of genotype-3 virus in swine, Madagascar. Am. J. Trop. Med. Hyg. 88: 329–338. doi: 10.4269/ajtmh.2012.12-0615 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.Thiry D., Mauroy A., Pavio N., Purdy M. A., Rose N., Thiry E., de Oliveira-Filho E. F.2017. Hepatitis E virus and related viruses in animals. Transbound. Emerg. Dis. 64: 37–52. doi: 10.1111/tbed.12351 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 64.Thiry D., Mauroy A., Saegerman C., Licoppe A., Fett T., Thomas I., Brochier B., Thiry E., Linden A.2017. Belgian Wildlife as Potential Zoonotic Reservoir of Hepatitis E Virus. Transbound. Emerg. Dis. 64: 764–773. doi: 10.1111/tbed.12435 [DOI] [PubMed] [Google Scholar]
  • 65.Trojnar E., Kästner B., Johne R.2020. No evidence of hepatitis E virus infection in farmed deer in Germany. Food Environ. Virol. 12: 81–83. doi: 10.1007/s12560-019-09407-y [DOI] [PubMed] [Google Scholar]
  • 66.Woo P. C. Y., Lau S. K. P., Teng J. L. L., Cao K. Y., Wernery U., Schountz T., Chiu T. H., Tsang A. K. L., Wong P. C., Wong E. Y. M., Yuen K. Y.2016. New hepatitis e virus genotype in bactrian camels, Xinjiang, China, 2013. Emerg. Infect. Dis. 22: 2219–2221. doi: 10.3201/eid2212.160979 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 67.Yonemitsu K., Terada Y., Kuwata R., Nguyen D., Shiranaga N., Tono S., Matsukane T., Yokoyama M., Suzuki K., Shimoda H., Takano A., Muto M., Maeda K.2016. Simple and specific method for detection of antibodies against hepatitis E virus in mammalian species. J. Virol. Methods 238: 56–61. doi: 10.1016/j.jviromet.2016.07.030 [DOI] [PubMed] [Google Scholar]
  • 68.Žele D., Barry A. F., Hakze-van der Honing R. W., Vengušt G., van der Poel W. H. M.2016. Prevalence of anti-hepatitis E virus antibodies and first detection of hepatitis E virus in wild boar in Slovenia. Vector Borne Zoonotic Dis. 16: 71–74. doi: 10.1089/vbz.2015.1819 [DOI] [PubMed] [Google Scholar]
  • 69.Zhang W., Yoshizaki S., Ami Y., Suzaki Y., Takeda N., Muramatsu M., Li T. C.2019. High prevalence of hepatitis E virus infection in imported cynomolgus monkeys in Japan. Jpn. J. Infect. Dis. 72: 429–431. doi: 10.7883/yoken.JJID.2019.129 [DOI] [PubMed] [Google Scholar]
  • 70.Zhang X. X., Qin S. Y., Zhang Y., Meng Q. F., Jiang J., Yang G. L., Zhao Q., Zhu X. Q.2015. First report of hepatitis E virus infection in sika deer in China. BioMed Res. Int. 2015: 502846. [DOI] [PMC free article] [PubMed] [Google Scholar]

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