Hendra virus infection

Previous authors: M M WILLIAMSON

Current authors: 
K HALPIN - Pathology and Pathogenesis Group Leader, BVSc, MVSc, MPH, MANZCVS, PhD, Australian Animal Health Laboratory, 5 Portarlington Road, East Geelong, Victoria, 3219, Australia
JR GIILKERSON - Professor of Veterinary Microbiology, BVSC, BSc (Vet), PhD, Department of Veterinary Biosciences, Faculty of Veterinary and Agricultural Science, University of Melbourne, Building 400, Corner of Flemington Road and Park Drive, Parkville, Victoria, 3010, Australia

GENERAL INTRODUCTION: PARAMYXOVIRIDAE AND PNEUMOVIRIDAE

Introduction

Hendra virus disease is caused by a virus that is very closely related to Nipah virus (see Nipah virus infection), and the two viruses contribute to the genus name Henipavirus. Hendra virus disease has only occurred in Australia, where fruit bats of the genus Pteropus are the wildlife reservoir host of the virus. Since it emerged in 1994 in the Brisbane suburb of Hendra,²⁸ there have been seven known human cases, four of which were fatal. Horses are the primary spill-over host and are extremely susceptible to infection and capable of amplifying the virus to high titres. All human cases have been infected after high level exposure to infected horse secretions or tissues, putting veterinarians, veterinary nurses and technicians, horse owners and people who work with horses, including trainers at a higher risk.¹⁹In response to this, a vaccine has been developed that prevents infection in horses, and thereby prevents infection in humans as well.²⁴

The geographical range of Hendra virus disease has spread along the eastern coast of Australia, reaching as far north as Port Douglas and as far south as Scone in New South Wales (NSW), a distance of more than 2000km^{7, 40}; disease has also been found approximately 300 km inland, in Chinchilla, Queensland. Most outbreaks, which occur on an almost annual basis, have only involved one or two horses and are often seasonal, with more spill-over events occurring in the cooler months. Direct transmission from the wildlife reservoir host to humans has not occurred, despite some humans, particularly wildlife carers, having very close contact with fruit bats.³⁴

While Hendra virus (HeV) is endemic in all four mainland species of Australian fruit bats belonging to the genus Pteropus, black flying foxes (Pteropus alecto) and spectacled flying foxes (Pteropus conspiculatus) are more commonly associated with HeV excretion than other species.^{6, 32} Virus excretion can occur any time of the year, with a winter peak found particularly in northern NSW and southern Queensland.⁷ As climatic conditions change and habitat is removed for more human use, the geographical distribution of fruit bats is expected to change, and along with that it is likely that more spill-over events will be reported in new geographical areas.²³

Aetiology

Hendra virus is a non-segmented negative-stranded RNA virus in the family Paramyxoviridae, genus Henipavirus. It was discovered in 1994 as the first known henipavirus.²⁷ This genus includes Nipah virus (NiV) and the more recently discovered Mojiang paramyxovirus⁴² and Cedar virus.²⁰ Cedar virus is not known to cause disease. Mojiang paramyxovirus was implicated in the death of three miners in China in 2012, following potential zoonotic transmission from rats.⁴²

Hendra virus is a large paramyxovirus with a genome consisting of 18, 234 nucleotides. . This increased genome size, compared to other paramyxoviruses, is in part due to the long untranslated regions (UTRs) at the 3′ end of most transcription units, similar to that observed in the filoviruses Marburg and Ebola.^{37, 38} Like all other viruses in the subfamily Paramyxovirinae, HeV has a genome length which is a multiple of six. Genomes whose lengths deviate from ‘the rule of six’ do not replicate efficiently. It has been proposed that the templates for transcription and replication are nucleoproteins in which each nucleoprotein subunit is associated with six nucleotides of genomic RNA.

The HeV genome consists of six genes that code for six major structural proteins, namely:  N nucleocapsid protein (N), phosphoprotein (P), matrix protein (M), fusion protein (F), glycoprotein (G) and large protein (L).

Sequence analysis of five HeV isolates from several outbreaks in horses indicates that the HeV genome is very stable and conserved , with at least 99 per cent nucleotide similarity between isolates when compared to the original isolate from 1994.²²

Hendra virus has the morphological and physicochemical properties typical of a paramyxovirus. It is pleomorphic in shape and enveloped with a herring-boned nucleocapsid.¹⁵ Virions are 40-600 nm in diameter.  Glycoprotein (G) and fusion (F) protein spikes project through a lipid envelope, but unlike NiV, the surface projections of HeV are predominantly double; NiV  surface projections are predominantly single.¹⁵

Culturing the virus from infected tissues in cell culture is relatively easy. However, HeV is a dangerous human pathogen and requires biosafety level 4 (BSL4) containment (see Diagnosis).

Limited work has been done to assess the stability of the virus. Both HeV and NiV exhibit an extremely broad tolerance to extremes of pH, with viable virus recovered after a 60 minute incubation in solutions ranging from pH 3 to  11 for NiV and pH 4 to  11 for HeV.⁹ In the same study, henipaviruses survived for more than four...