By Laurie Dixon

Targeting the "envelope" around the Hendra virus may be the key to effective treatment of the deadly disease, researchers have revealed.



Dr Matteo Porotto Dr Matteo Porotto

Scientists at Weill Cornell Medical College in New York City have announced a breakthrough in efforts to find a treatment effective against the deadly related viruses, Hendra and Nipah.

Hendra and Nipah are members of the henipavirus family. They are highly pathogenic and emerged from flying fox bats in the mid and late-1990s, respectively.

Hendra, found only in Australia, is capable of being transmitted from bats to horses and then to people.

Of the seven known cases in people, all centred on Queensland, four proved fatal. The last two victims were equine veterinarians.

There have been 40 known infections in horses, all of which resulted in the horses either dying or being euthanised.

Nipah virus causes fatal brain swelling in up to 70 per cent of human cases. There are seasonal outbreaks in Asia with person-to-person transmission now becoming a primary mode of infection.

The New York researchers say they have identified a potential new treatment for the viruses, for which there is currently no proven treatment or vaccine available.

They say their approach could also lead to new therapies for measles, mumps and the flu.

The new research appears in this week's edition of the open-access journal, PLos ONE.

Dr Matteo Porotto, the study's lead author and assistant professor of microbiology in pediatrics at the medical college, said their new strategy to prevent and treat these infections that may also be broadly applicable for other "enveloped" viral pathogens.

Such viruses are characterised by an outer wrapping that comes from the infected host cell.

Dr Porotto says it is difficult to treat these pathogens because their "envelope" helps the virus survive and infect other cells.

"We know that enveloped viruses must fuse their membrane with the target cell membrane in order to initiate infection, and blocking this step can prevent or treat infection, as has been clinically validated for the HIV virus."

Building on their past work, the team demonstrated in this study that the addition of a cholesterol group to peptides that are active against Nipah virus dramatically increases their antiviral effect.

The approach works by using the cholesterol-tagged peptides to target the membrane where the fusion occurs.

There, the peptides interact with the fusion peptide before it inserts into the target cell membrane, disrupting the crucial membrane fusion process and preventing infection.

"The cholesterol-tagged HRC-derived peptides cross the blood-brain barrier and help prevent and treat the infection in animals for what would otherwise be fatal Nipah virus encephalitis," he says.

"This suggests that they are promising candidates for the prevention or therapy of infection by Nipah and other lethal paramyxoviruses and may lead to better treatments for people affected by similar viruses including the measles, mumps and the flu."

The new treatment was successfully tested in an animal model demonstrating central nervous system symptoms similar to those seen in humans.

Dr Anne Moscona, who took part in the study, said: "It's crucial that we find treatments for the Nipah and Hendra viruses.

"In addition to acute infection, they can cause asymptomatic infection in as many as 60 per cent of exposed people.

"They may also lead to late-onset disease or relapse of encephalitis [braining swelling] years after initial infection, as well as persistent or delayed neurological problems."

Porotto said the Hendra and Nipah viruses were of great concern.

"The Hendra virus is highly fatal and is a considered a potential agent of bioterrorism. It currently poses a serious threat to livestock in Australia, where sporadic and deadly transmission to humans has occurred, with the potential for broader dissemination."

Additional co-authors include Christine Yokoyama, Aparna Talekar, Ilaria DeVito, Laura Palermo and Min Lu from Weill Cornell Medical College; Barry Rockx and Heinz Feldmann from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana; Riccardo Cortese from CEINGE, Naples, Italy; and Antonello Pessi from PeptiPharma, Rome, Italy.