There have been numerous waves of epidemics, from the Spanish Influenza early in the 20th century to the recent H1N1 swine flu scare. Such waves of sickness seem to appear out of nowhere and attack humans. Particularly, it is the viruses that the average American has never heard of and do not worry about on a regular basis that can cause widespread disease.
The Nipah and Hendra are such viruses.
These viruses are not as well known in the U.S. as they are in South Asia, but their introduction into the U.S. population could be a major public health concern.
“They are potential agents of bioterrorism,” explained Prof. Matteo Porotto, microbiology in pediatrics, of Weill Cornell Medical College. “Fatality is from 70 to 80 percent, and they can be transmitted from human to human.”
Because of their potential threat, there is “a lot of incentive from NIH [National Institutes of Health] to fund research of this problem,” Porotto said. His team also receives funding from the Rockefeller Foundation and Weill Cornell Medical College for using surrogate, non-pathogenic systems in their research.
Nipah and Hendra are “enveloped” viruses in the Henipavirus genus, naturally hosted by fruit bats in Southeast Asia. Porotto suspects that “the expansive farming, especially in Malaysia, where wild animals were coming in close contact with farm animals, is the root of the cause.”
Nipah can be transmitted from animal to human and from human to human, causing encephalitis (inflammation of the brain) and possibly death. Nipah is most commonly found in pigs in Malaysia, but “it also has a huge host range, as it can infect monkeys, cats, ferrets, and can kill all these animals,” explained Porotto. There has been several outbreaks, including one in 1999 among pig farmers in Malaysia.
Hendra can be transmitted from horses to people and causes fatal respiratory and neurological diseases. There have been numerous outbreaks in Australia.
The Nipah and Hendra viruses proliferate inside the human body by fusing their membrane with a cell membrane, entering the cell, and controlling the cell’s mechanisms to their advantage.
Until now, no treatment or vaccine has been made available.
Porotto and his team discovered a potential new treatment, however. “Because of the ability of fusion, it can enter the membrane and enter the cell. We block the first step before they enter,” he explained.
Tagging a cholesterol group to a HRC peptide on the cell membrane dramatically increases the antiviral effect against Nipah and Hendra.
“The cholesterol brings the peptide close the membrane,” Porotto said. The HRC peptide, which is derived from small pieces of viral glycoproteins, can then interact with the viral membrane, thus preventing the virus from entering the cell.
In practical application, the cholesterol is tagged to the HRC peptide by chemical synthesis. Porotto explained, “the cholesterol glues itself onto the membrane.” The cholesterol is attracted to the membrane because they are both hydrophobic.
The cholesterol-peptide complex is placed in saline solution and injected into the animal for about fourteen days. The peptide can then travel in the bloodstream and block the virus.
Though the Nipah and Hendra viruses are not directly relevant to the U.S. population today, Porotto and his team decided to research them because their new strategy to block the viruses can be applied to other more common “enveloped” viruses, such as the measles and mumps.
“Despite the fact that there is a good vaccine for the measles and mumps, there are still cases of encephelitis. Even in the presence of antibodies, there is no cure for that,” lamented Porotto.
Encephelitis from the measles and mumps is also more common in children. Though “it is a strategy that is working for this virus that is not important for the U.S. population, it is a study that can help the U.S. population [indirectly].”
Porotto and his team did not originally plan to study the Nipah and Hendra viruses. They were exploring pediatric pathogens, such as the measles and mumps. Though they did not have a direct hypothesis at first, they started to explore the mechanism of the HRC peptide. This research “brought us to study more about the Nipah and Hendra.”
In the future, Porotto hopes to “apply this strategy to other viruses, like ebola,” another lethal virus.
Porotto sees potential for research stemming from his own. “One of the outcomes of our work is that this peptide is able to go into the central nervous system.
“This is unique; we are exploring the determinants of this, so we can apply this to different viruses, including HIV and measles. We are trying to move our discovery to other pathogens, as well as to cure the existing diseases,” Protto said.
Original Author: Yoshiko Toyoda