Scientists at Weill Cornell Medical College have identified a potential new treatment for the Nipah and Hendra viruses, two lethal and emerging viruses for which there is currently no treatment or vaccine available. The approach could also lead to new therapies for measles, mumps and the flu.
The new research appears in the online journal PLoS Pathogens, published by the Public Library of Science.
The Nipah and Hendra viruses are members of the genus Henipavirus, a new class of virus in the Paramyxoviridae family, which includes the measles and the human parainfluenza virus (HPIV) that causes pediatric respiratory disease. The henipaviruses are carried by fruit bats (flying foxes) and are capable of causing illness and death in domestic animals and humans.
"These viruses are 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," says Dr. Matteo Porotto, the study's lead author and assistant professor of microbiology in pediatrics at Weill Cornell Medical College. "And the Nipah virus, which causes fatal encephalitis in up to 70 percent of human cases, causes seasonal outbreaks in Asia with person-to-person transmission now becoming a primary mode of infection. This virus could certainly cause global outbreaks."
Dr. Porotto and colleagues present a new strategy to prevent and treat these infections that may be broadly applicable for other "enveloped" viral pathogens, characterized by an outer wrapping that comes from the infected host cell. The new treatment was successfully tested in an animal model demonstrating central nervous system symptoms similar to those seen in humans.
Dr. Anne Moscona, professor of pediatrics and microbiology & immunology at Weill Cornell Medical College, vice chair of pediatrics for research at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, chief of pediatric infectious diseases and co-corresponding author of the paper, says, "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 percent of exposed people. They may also lead to late-onset disease or relapse of encephalitis years after initial infection, as well as persistent or delayed neurological problems."
According to Dr. Porotto, 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 HRC 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," Dr. Porotto reports. "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."
Additional co-authors include Christine C. Yokoyama, Aparna Talekar, Ilaria DeVito, Laura M 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, MT; Riccardo Cortese from CEINGE, Naples, Italy; and Antonello Pessi from PeptiPharma, Rome, Italy.
- Matteo Porotto, Barry Rockx, Christine C Yokoyama, Aparna Talekar, Ilaria DeVito, Laura M Palermo, Jie Liu, Riccardo Cortese, Min Lu, Heinz Feldmann, Antonello Pessi, Anne Moscona. Inhibition of Nipah Virus Infection In Vivo: Targeting an Early Stage of Paramyxovirus Fusion Activation during Viral Entry. PLoS Pathogens, 2010; DOI: 10.1371/journal.ppat.1001168
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