Nav: Home

Potent antibody curbs Nipah and Hendra virus attack

September 30, 2019

A new monoclonal antibody has been shown to impede the fusion machinery henipaviruses use to merge with the membrane of cells they are attempting to breach. The antibody halts the attack by blocking membrane fusion and the injection of the viral genome into the host cell.

The researchers said they hope that these types of laboratory discoveries will pave the way toward preventing Nipah virus and Hendra virus infections or provide a solution for post-exposure therapy.

At present, there are no vaccines or licensed treatments for these diseases in people. Some patients have been given experimental therapies under compassionate-use exceptions. Veterinary medicine approaches, and farming and wildlife health measures, have also been instituted to control the spread of the viruses in animals and people.

These difficult-to-manage infections emerged as animal-to-human transmitted diseases in the mid- 1990s. Outbreaks have since occurred in Australia, Malaysia, the Philippines, Singapore, Bangladesh, and Kerala and West Bengal, India.

Although no related human diseases have been reported in Africa, henipavirus antibodies have been found there in both people and bats, an indication that the virus is circulating in this continent. This suggests the possibility of henipavirus disease outbreaks arising there in the future.

Both Nipah and Hendra can cause severe respiratory illness and brain inflammation. Fatality rates during outbreaks have ranged from 50 percent to 100 percent.

"More than two billion people live in regions threatened by henipavirus outbreaks," the researchers noted in their paper. Their report is published in the Sept. 30 issue of Nature Structural & Molecular Biology.

The anti-fusion monoclonal antibody studies were headed by senior researchers David Veesler of the University of Washington School of Medicine's Department of Biochemistry in Seattle, and Christopher Broder of the Uniformed Services University's Department of Microbiology and Immunology in Bethesda, Maryland.

Ha V. Dang of the UW and Yee-Peng Chan of USU were the lead authors. Also contributing were scientists from the Sealy Center for Vaccine Development at the University of Texas, Galveston.

Among the chief carriers of Nipah virus and Hendra virus are large, fruit-eating bats, called flying foxes. In Australia, horses have come down with Hendra virus after bats contaminated their food or water. Owners, trainers and veterinarians caught the virus while caring for the sick horses.

Nipah virus has been transmitted from bats to pigs in Malaysia and Singapore, and then from the pigs to farmers. People have also been infected with the virus from drinking palm sap that had attracted thirsty bats in Bangladesh and parts of India. Food-borne Nipah virus illnesses now occur seasonally almost every year in Bangladesh.

Nipah virus and Hendra virus are RNA viruses in the family of paramyxoviruses, making them distant cousins of human pathogens such as measles, mumps, respiratory syncytial, and Newcastle viruses.

Many paramyxoviruses have spikey envelopes. The spikes sport a viral-attachment glycoprotein and a fusion glycoprotein. Unlike many other paramyxoviruses, henipaviruses can infect a variety of mammals. These viruses are different and dangerous.

The researchers explained that Nipah and Hendra viruses enter animal or human cells through the concerted action of the attachment and fusion glycoproteins.

After the virus lands on the cell surface, the attachment protein undergoes a shape change that prompts the fusion protein to insert a fusion peptide into the cell membrane.

Afterward, the fusion protein refolds into a more stable conformation that staples together the viral and cellular membranes. A tunnel-like pore is forged for the virus' genetic material to slip into the cell interior to initiate infection.

The body's own humoral immune defenses, mediated by antibody molecules, target vital parts of the merging machinery to keep the virus at bay. In fact, the measles vaccine, the researchers said, creates antibodies that protect against a similar type of viral breach.

Other researchers have discovered antibodies that block attachment of Nipah and Hendra viruses to host cells. One of these antibodies protected animals, even when administered several days after infection.

In this latest study, scientists isolated from mice, and then humanized, a potent monoclonal antibody that neutralizes both Nipah and Hendra viruses. They then studied its mode of action using molecular imaging via cryo-electron microscopy and biochemical and cellular experiments.

These studies revealed that the antibody recognizes and binds to a specific area of the viral membrane fusion machinery during the pre-fusion stage.

This epitope (an antibody target site on the virus) is present in both the Nipah and the Hendra viruses. This explains why the same antibody protects against both viruses. Binding of the antibody prevented membrane fusion and thereby kept the viral material out of the cell.

The research team is hopeful that future planned experiments that combine different antiviral monoclonal antibodies that attack distinct targets on Nipah and Hendra viruses will demonstrate enhanced therapeutic benefit to infected individuals.
-end-
Facilities for the study reported Sept. 30 included the Arnold and Mabel Beckman cyroEM Center and Proteomics Resource at the University of Washington, and the Advanced Light Source at Lawrence Berkeley National Laboratory.

University of Washington Health Sciences/UW Medicine

Related Bats Articles:

Vampire bats give a little help to their 'friends'
Vampire bats could be said to be sort of like people -- not because of their blood-sucking ways, but because they help their neighbors in need even if it's of no obvious benefit to them.
How bats relocate in response to tree loss
Identifying how groups of animals select where to live is important for understanding social dynamics and for management and conservation.
Bats use private and social information as they hunt
As some of the most savvy and sophisticated predators out there, bats eavesdrop on their prey and even on other bats to collect a wide variety of information as they hunt.
There are way more species of horseshoe bats than scientists thought
Horseshoe bats are bizarre-looking animals with giant ears and elaborate flaps of skin on their noses that they use like satellite dishes.
What a group of bizarre-looking bats can tell us about the evolution of mammals
Bats with skulls and teeth adapted to a wide range of diets are helping scientists understand how major groups of mammals first evolved.
Fruit bats can transform echoes into images
A new Tel Aviv University study finds that fruit bats actually integrate vision and echolocation to flourish in the dead of night.
Bats' brains sync when they socialize
The phrase 'we're on the same wavelength' may be more than just a friendly saying: A new study by University of California, Berkeley, researchers shows that bats' brain activity is literally in sync when bats engage in social behaviors like grooming, fighting or sniffing each other.
Bats have an ambulance in their ears
'The Doppler shift patterns produced by the ear motions could give these bat species the option to concentrate their energy in a narrow frequency band yet be also able to tell target direction.'
These fruit bats trade food for sex
Egyptian fruit bat females living in captivity will consistently take food right from the mouths of their male peers.
Vaccination may help protect bats from deadly disease
A new study shows that vaccination may reduce the impact of white-nose syndrome in bats, marking a milestone in the international fight against one of the most destructive wildlife diseases in modern times.
More Bats News and Bats Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#541 Wayfinding
These days when we want to know where we are or how to get where we want to go, most of us will pull out a smart phone with a built-in GPS and map app. Some of us old timers might still use an old school paper map from time to time. But we didn't always used to lean so heavily on maps and technology, and in some remote places of the world some people still navigate and wayfind their way without the aid of these tools... and in some cases do better without them. This week, host Rachelle Saunders...
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.