Tag Archives: secreted frizzled related protein

To facilitate the pathogenesis studies the infectivity titer of

To facilitate the pathogenesis studies, the infectivity titer of the rHEV-3 challenge stock was assayed as 103 RID50 per ml. In view of the absence of a cell culture system, this standardization of an infectious stock of rHEV-3 could be especially meaningful for future studies on the pathogenesis and prevention of rHEV-3. This study showed clearly that infection of rabbits with 102 RID50 can lead to the development of hepatitis. By comparison, rabbits had little or no biochemical evidence of hepatitis when challenged by 10 RID50 or lower doses of virus. This is consistent with the previous research on HEV infection of cynomolgus macaques, which showed that biochemical hepatitis was strictly correlated with the dose of infectious HEV (Tsarev et al., 1994). It is also worthy of note that at lower doses of inoculum, later fecal shedding and sero-conversion both occurred, as well as fecal shedding lasting for a shorter time. Collectively, these data demonstrate that HEV infections are virus dose dependent and that the rate of inducing hepatitis increases with virus dose.
In secreted frizzled related protein to the apparent inability of hHEV-3 (JRC-HE3) to infect rabbits, rHEV-3 both induces clinical disease and appears to have similar pathogenesis to that seen in HEV infected humans. Notably, the positive signs of HEV replication observed in lung tissue, also noted in a previous study (Han et al., 2014), indicates that lung injury might be associated with HEV infection. This leads to the proposal that the possibility of HEV infection should be considered in patients with pulmonary disorders of unknown etiology.

Conflict of interests

Acknowledgments
This work was supported by the Beijing Natural Science Foundation (Grant number 7162103) and the National Science Foundation of China (Grant Number 81401746). We are grateful to Professor Malcolm A. McCrae of University Warwick, UK for proofreading the manuscript. We would like to thank Dr Ning-Shao Xia, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, The Key Laboratory of the Ministry of Education for Cell Biology and Tumour Cell Engineering, Xiamen University for generously providing us with the human HEV-3 (JRC-HE3, Genbank AB630971) strain.

Introduction
Akabane virus (AKAV) is a segmented, negative-sense, single-stranded RNA virus. It is classified taxonomically in the genus Orthobunyavirus, family Bunyaviridae (Plyusnin et al., 2012) and, like Schmallenberg virus (SBV) which emerged in 2011, it is a member of the Simbu serogroup of orthobunyaviruses (Hoffmann et al., 2012; Kinney and Calisher, 1981). AKAV has been isolated on several occasions from mosquitoes but biting midges (Culicoides spp.) appear to be the principal vectors (Jennings and Mellor, 1989). AKAV infects a wide range of wild ruminants and livestock including cattle, sheep, goats, buffalo, deer, horses and pigs (Kirkland, 2002; Huang et al., 2003). However, secreted frizzled related protein Akabane disease occurs primarily in cattle, and more rarely sheep and goats, manifesting as abortions, stillbirths and congenital abnormalities in newborns. Clinical signs include arthrogryposis and hydranencephaly (A–H syndrome), with the highest incidence and severity of disease when infection occurs during the mid-term of gestation. Post-natal infection of calves with some strains of the virus can also cause encephalomyelitis (Oem et al., 2012a,b). There has been no report of AKAV infection in humans (Kirkland, 2002).
AKAV is known to be widely distributed across tropical and subtropical areas of East Asia as well as Australia, the Middle-East and Africa (Cybinski et al., 1978; Taylor and Mellor, 1994). The virus was first isolated from mosquitoes (Aedes vexans and Culex tritaeniorhynchus) collected in 1959 in Gumma Prefecture, Japan (Oya et al., 1961). Although the collection occurred during an outbreak of disease resulting in congenital malformation in cattle, an etiological link between the virus and this disease was not proposed until much later (Kurogi et al., 1975). A similar serious outbreak in Japan from 1972 to 1973 resulted in more than 31,000 cases of abortion, stillbirth and congenital A-H syndrome; the outbreak continued through 1974–1975 (Kurogi et al., 1975). AKAV was subsequently isolated from biting midges (Culicoides brevitarsis) in Australia in 1968 and an association between neutralising antibodies to AKAV and A-H syndrome in New South Wales was reported (Doherty et al., 1972; Hartley et al., 1975). AKAV isolations from cattle or biting midges have since been reported from Japan (Kurogi et al., 1987), Australia (St George et al., 1978), Chinese Taipei (Liao et al., 1996) and South Korea (Bak et al., 1980). Molecular detection of AKAV RNA has also been detected from biting midges and affected animals in Israel (Stram et al., 2004) and Turkey (Oğuzoğlu et al., 2015).