Study offers new clues to killer viruses
Friday, 08 July, 2005
Virologists have identified the cellular receptor that serves as a portal for infection by deadly bat-borne Henipa viruses, which have caused human deaths in Australia, Malaysia, Singapore and Bangladesh during the past decade.
Hendra virus killed two humans and more than a dozen horses in 1994, including prominent Brisbane horse trainer Vic Rail, and the husband of a Rockhampton veterinarian who had helped his wife treat an infected horse. Nipah virus ravaged piggeries in the central part of peninsular Malaysia in 1998/99, killing more than 100 people and hundreds of pigs, and forcing the culling of more than 1 million pigs to control spread of the disease.
Senior virologist Dr Bryan Eaton, and molecular biologist Dr Linfa Wang, of CSIRO Livestock Industries' Australian Animal Health Laboratory in Geelong, were involved in study, published this week in Proceedings of the National Academy of Sciences, that identifies the Ephrin-B2 receptor as the viruses' infection target.
Eaton said the discovery, which could help researchers develop a vaccine or drugs to block infection by both viruses, is even more important in light of repeated small outbreaks of another, Nipah-like virus in Bangladesh during the past three years.
Like other Henipaviruses, the Bangladesh virus is distantly related to the human paramyxovirus that causes mumps, and the morbilliviruses that cause measles in humans, rinderpest in cattle and distemper in dogs and seals.
Eaton said the Bangladesh virus is a concern because of its very high mortality, and a clear pattern of human-to-human transmission in families. In Bangladesh, an initial case of infection in a local religious leader had resulted in 18 deaths among 25 people with whom he had been in contact within his extended family. Hendra and Nipah outbreaks had previously involved horse-to-human, or pig-to-human transmission.
Eaton said that in Australia and Malaysia, Henipaviruses are carried by flying foxes and fruit bats in the pan-tropical genus Pteropus. Australia has four species, and a significant percentage of bats in each species have Hendra virus antibodies.
Nipah virus antibodies have been identified in Pteropus bats throughout south-east Asia, including, more recently, bats in Cambodia.
"There's considerable variation in the viruses making their way from various bat species to humans and other mammals, but there were at least two episodes of transmission in Malaysia, and maybe only one of them took off explosively," Eaton said. "We know so little about the ecology of these viruses that we don't even know how they are transmitted from bat to bat, let alone to other mammals."
The bats show no signs of infection. Henipa viruses have an extremely broad host range, spanning six mammalian orders -- including primates.
Eaton said the viruses bind to the Ephrin-B2 molecule and then fuse to the host cell membrane using two coat proteins. Its G protein is the attachment ligand, while the F protein drives the fusion of the virus membrane with the cell membrane.
"The fact that both viruses exploit the same receptor provides an explanation for their similar systemic pattern of infection," he said. "Ephrin-B2 is widely distributed in vascular endothelial cells.
"It is now recognised as having an important role in the development of the vasculature and neural systems, by facilitating cell-to-cell contact and two-way signalling between adjacent cells.
"If you knock out the receptor or its ligand in mice, it disrupts facial and neural development. But it was around long before the first vertebrates appeared -- it has antecedents in sponges."
Although the receptor is highly conserved in mammals, the same virus can produce different modes of infection, depending on the host species -- Eaton said it tends to cause encephalitis in humans, but respiratory infections in pigs and horses.
Rabbits injected with the G protein develop neutralising antibodies, suggesting it should be feasible to develop a vaccine, but research has also shown that peptides that mimic a 40-amino acid stretch of the virus' surface F protein disrupts its ability to bind to the host cell. This peptide could be used to block infection by preventing the virus' entry and replication.
Free meningococcal B vaccines coming to the NT
The Northern Territory Government has confirmed the rollout of a free meningococcal B vaccine...
Mouth bacteria linked to increased head and neck cancer risk
More than a dozen bacterial species that live in people's mouths have been linked to a...
Life expectancy gains are slowing, study finds
Life expectancy at birth in the world's longest-living populations has increased by an...