- A new monoclonal antibody has been discovered that prevents the transmission of Nipah and Hendra viruses
- The antibody blocks transmission by preventing virus attachment and fusion to host cells
- This could lead to novel therapies for preventing Nipah and Hendra virus infections
Nipah and Hendra
virus transmission can be inhibited by a new monoclonal antibody, which
prevents the viruses from attaching and fusing to host cells, thereby blocking
the transfer of the viral genetic material and thus halting disease
The findings have been reported by researchers from the University of Washington School of Medicine, USA. The research team is optimistic that this type of lab-based research could lead to the development of new therapies against Nipah and Hendra viruses, which are collectively known as henipaviruses.
The study findings have been published in Nature Structural & Molecular Biology.
Study TeamThe study was jointly led by Dr. David Veesler, PhD and Dr. Christopher C. Broder, PhD. Dr. Veesler is an Assistant Professor in the Department of Biochemistry at the University of Washington School of Medicine in Seattle, while Dr. Broder is a Professor and Chair in the Department of Microbiology and Immunology at the Uniformed Services University, Bethesda, MD, USA.
Epidemiology of Nipah and Hendra VirusesNipah and Hendra are RNA (ribonucleic acid) viruses belonging to the family Paramyxoviridae. Other paramyxoviruses include measles, mumps, parainfluenza, and Newcastle disease viruses, as well as respiratory syncytial virus (RSV). Nipah and Hendra viruses are spread by infected fruit bats, also known as flying foxes.
Both the Nipah virus and Hendra virus cause severe respiratory infections and brain inflammation. Case fatality rates can range anywhere between 50 percent and 100 percent. Currently, there are no licensed vaccines or drugs for treating these viral diseases. The mainstay of prevention involves maintaining a healthy livestock and wildlife management for preventing animal to human transmission of these viruses.
Major Outbreaks of Nipah and Hendra VirusesThe first outbreak of Nipah occurred in Malaysia in 1998, where the virus was transmitted from fruit bats to pigs and then to humans. Subsequent outbreaks have occurred in Singapore, India, and Bangladesh. The Singapore outbreak occurred due to the spread of the virus from the initial Malaysian outbreak to Singapore.
In the outbreaks that occurred in India and Bangladesh, the infection spread to humans by drinking palm sap that had become infected with the virus from fruit bats. In India, Nipah outbreaks have been reported from West Bengal and Kerala, while in Bangladesh, the virus has become endemic and seasonal outbreaks occur almost every year.
Hendra virus outbreaks have been reported from Australia, where horses have fallen ill due to consumption of food and water contaminated by fruit bats. Subsequently, the people associated with the horses, including trainers, owners and veterinarians, also became infected with the virus due to close contact with the sick horses.
Presence of Nipah and Hendra virus antibodies among humans and fruit bats in Africa indicates that these viruses are circulating in this continent, although no human cases have so far been detected. Therefore, the occurrence of Nipah and Hendra outbreaks in Africa in the future is a real possibility. Importantly, over 2 billion people across the globe live in areas where Nipah and Hendra outbreaks can potentially occur.
Mechanism of Infection by Nipah and Hendra VirusesParamyxoviruses are enveloped viruses that have spike-like surface projections made-up of glycoproteins, of which there are two major types. One type helps in viral attachment, while the other helps in fusion to the host cell surface. With concerted efforts by the attachment and fusion glycoproteins, a tunnel-like pore is created at the virus-cell interface, through which the viral RNA is injected into the host cells to initiate a round of infection.
As opposed to many other paramyxoviruses, the host-range of Nipah and Hendra viruses is much broader, allowing them to infect a large variety of mammalian species, which makes them very dangerous. However, the body's humoral immune response, mediated by antibodies, keeps these viruses in check by blocking their attachment to the host cells, thereby preventing viral transmission.
Major Findings of the StudyThis study is based on previous studies, which showed that specific antibodies could block the attachment of Nipah and Hendra viruses to host cells. Importantly, one of these antibodies was capable of protecting infected animals even after several days post infection.
In this study, the researchers discovered a specific monoclonal antibody from mice and humanized it so that it could be administered to humans. This humanized monoclonal antibody was highly potent and could neutralize both Nipah and Hendra viruses.
Mechanism of Action of the New Monoclonal AntibodyThe mechanism of action of the newly discovered monoclonal antibody was elucidated using the latest biochemical and cellular techniques, as well as molecular imaging using cryogenic electron microscopy. These state-of-the-art techniques revealed that the monoclonal antibody recognizes and binds to a specific region of the viral fusion machinery prior to the fusion of the viruses to host cells.
Both Nipah and Hendra viruses possess the same epitope on their surface, which functions as the target site for attachment of antibodies to bring about viral neutralization. This sharing of the same epitope explains why the same antibody is capable of conferring protection against both viruses. Binding of the monoclonal antibody to the epitope blocks membrane fusion, preventing injection of the viral RNA into the host cells, thereby halting the infection process.
ConclusionBased on the current findings, the researchers are optimistic that combining various antiviral monoclonal antibodies having different specificities for distinct targets on Nipah and Hendra viruses, could offer enhanced therapeutic benefits for infected individuals.
Funding SourceThe study was funded by multiple organizations and funding agencies, including the NIH/National Institute of Allergy and Infectious Diseases, the NIH/National Institute of General Medical Sciences, the Burroughs Wellcome Fund, the Netherlands Organization for Scientific Research, the European Molecular Biology Organization, and the Pew Charitable Trusts.
- An Antibody against the F Glycoprotein Inhibits Nipah and Hendra Virus Infections - (https://doi.org/10.1038/s41594-019-0308-9)