Subfamily: Orthohepevirinae

Genus: Paslahepevirus

Distinguishing features

Members of the genus Paslahepevirus are phylogenetically distinct from other viruses in the subfamily, and have a different host range, being found in humans, as well as in a wide range of domestic and wild mammals (pig, wild boar, cow, deer, rabbit, camel).

Biology

Hepatitis E virus (HEV) is associated in humans with outbreaks and sporadic cases of acute hepatitis. The virus is considered endemic in tropical and subtropical countries of Asia, and Africa, as well as Mexico, but antibody prevalence studies suggest a global distribution for this virus. Large outbreaks that may involve thousands of cases of acute hepatitis occur in endemic regions. Sporadic zoonotic cases are more common in industrialized countries. Human-to-human transmission seems rare in hepatitis E epidemics although infections can be transmitted by blood transfusion or transplantation (including xenotransplantation) from acutely infected donors (Hewitt et al., 2014, Huzly et al., 2014). Hepatitis E virus can be vertically transmitted from mother to foetus.

Members of the species Paslahepevirus balayani have been assigned to 8 different genotypes, HEV-1 to HEV-8 (Smith et al., 2020). Of these genotypes; HEV-1, HEV-2, HEV-3 and HEV-4 are most commonly associated with HEV infection in humans. Genotypes HEV-1 and HEV-2 are restricted to humans, whereas genotypes HEV-3 and HEV-4 have a broader host range and are zoonotic. Interspecies transmission of genotypes HEV-3 and HEV-4 between pigs and non-human primates has been demonstrated experimentally. Pig handlers in both developing and industrialized countries are at increased risk of HEV infection. Human strains from Southern Asia typically belong to HEV-1 and are epidemically transmitted faecal-orally. Strains of HEV-1 in Western Europe are usually associated with recent travel to southern Asia or Africa. Very few strains of HEV-2 have been described, but these comprise a range of locations (Mexico and Africa) and are associated with epidemic faecal-oral transmission.

Genotypes HEV-3 and HEV-4 have been detected in and/or isolated from humans, pigs and deer in Europe, America and Asia, with human infection presumed to result from the consumption of raw or undercooked pig meat or products although a direct link has seldom been proven. Exceptions are the consumption of figatellu sausage in France (Colson et al., 2010) and raw deer liver in Japan (Tei et al., 2003, Takahashi et al., 2004). Recent studies have expanded the host range of HEV-3 to include goats (Di Martino et al., 2016), rats (Kanai et al., 2012, Lack et al., 2012) and bottlenose dolphins (Montalvo Villalba et al., 2017), and of HEV-4 to include cattle (Hu and Ma 2010, Huang et al., 2016) and sheep (Wu et al., 2015). A variant of HEV-3 found in rabbits has distinctive insertions in ORF1 (Zhao et al., 2009) and has also been detected in a human (Izopet et al., 2012). HEV-5 and HEV-6 have only been detected in wild boar in Japan (Takahashi et al., 2014). HEV-7 has been detected in dromedary camels (Woo et al., 2014) with one report of human infection (Lee et al., 2016). HEV-8 has only been detected in Bactrian camels in China (Woo et al., 2016).

Human infection with HEV is typically self-limiting and frequently asymptomatic; studies of blood donors in several European countries report that there are typically no or minor symptoms with infrequent mild elevation of liver enzymes (Vollmer et al., 2012, Juhl et al., 2014, Tedder et al., 2016). The incubation period for hepatitis E ranges from 15 to 40 days. Symptoms include diarrhoea, epigastric pain, nausea, hepatomegaly, splenomegaly and vomiting. The icteric phase of illness begins with jaundice, dark urine and clay-coloured stools. Extrahepatic manifestations are associated with the brain, central nervous system, muscle tissue, kidney, pancreas and placenta (Dalton et al., 2011, Kamar et al., 2013, Bose et al., 2014). Mortality ranges from 0.4% to 2% among immunocompetent individuals, although it may be as high as 20% to 30% among women in the second or third trimester of pregnancy.

Exposure to HEV infection is widespread with serological evidence of infection in a majority of individuals by the age of 20–40 years (Izopet et al., 2015). Following acute infection with HEV any symptoms usually resolve and the virus is cleared in a little over 6–7 weeks (Tedder et al., 2016). However, chronic infection (viremia for >3 months) has been described in immunosuppressed individuals (Haagsma et al., 2008, Kamar et al., 2008). In recent years it has been recognized that a proportion of infected individuals suffer from neurological symptoms (Dalton et al., 2016).

In pigs, infections with HEV are asymptomatic. Viremia lasts for 1–2 weeks, with faecal viral shedding occurring 1–2 weeks after infection and persisting for up to 8 weeks. Hepatic changes are minimal; sites of extrahepatic replication have been identified in the small intestine, colon, and hepatic and mesenteric lymph nodes (Williams et al., 2001).

Species demarcation criteria

Members of different species in the genus are phylogenetically distinct based upon analysis of ORF1 codon positions 1−450 (methyltransferase), ORF1 codon positions 971–1692 (RNA-directed RNA polymerase) and ORF2 codon positions 121−473 (capsid protein not including the region encoded by the overlapping ORF3). Members of different species may also have different host ranges, although limited data is available.

Related, unclassified viruses

Virus names and virus abbreviations are not official ICTV designations.

The tree shrew virus has not been classified because it is unaccompanied by a publication giving details of its origin.