Unmasking Nipah Virus: A Deadly Zoonotic Threat and the Race for a Vaccine

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Globally, NiV remains a significant concern due to its high mortality rate, which can vary between 40% and 100%, depending on the outbreak.
As of 2024, the Nipah virus (NiV) has resurfaced with notable outbreaks in South Asia, particularly in India, and Bangladesh.


Nipah Virus

Nipah virus (NiV) is a zoonotic paramyxovirus belonging to the Henipavirus genus, first identified in Malaysia in 1998 during an outbreak. It primarily causes severe encephalitis and respiratory diseases in humans. Its reservoir hosts are fruit bats, particularly the Pteropus species, and it can be transmitted from animals to humans through direct contact or via contaminated food, such as raw date palm sap. Human-to-human transmission is also possible. NiV is categorized as a biosafety level 4 (BSL-4) pathogen due to its high mortality rate, which can range from 40% to 75%, and its potential for causing global pandemics due to its high mutation rate.

Nipah Virus Entry

Nipah virus enters the human body primarily through the respiratory tract. The virus utilizes two glycoproteins on its envelope, G (attachment) and F (fusion), to bind to host cell receptors, ephrin-B2 and ephrin-B3. These receptors are abundantly expressed in endothelial cells, neurons, and smooth muscle, allowing the virus to infect a wide range of cells. Once the G protein binds to the ephrin receptors, the F protein facilitates the fusion of the viral envelope with the host cell membrane, allowing viral entry. After entering the cell, the virus rapidly spreads, either through cell-to-cell fusion, forming multinucleated syncytia, or via the bloodstream.

Nipah Virus Replication

Replication begins after the virus enters the host cell. The viral RNA is released into the cytoplasm, where it undergoes transcription and replication. The viral RNA-dependent RNA polymerase (L protein) and nucleoprotein (N) drive the production of viral mRNAs. The viral M protein assists in assembling new viral particles, while nonstructural proteins such as C, P, and V play crucial roles in regulating replication and immune evasion. The virus predominantly replicates in the respiratory epithelium and endothelial cells, later spreading to the central nervous system (CNS) via the bloodstream, leading to severe complications such as encephalitis.

Immune Evasion Techniques

Nipah virus employs several strategies to evade the host's immune response. It suppresses the production of interferon (IFN), a key antiviral molecule, by targeting pathways responsible for IFN signaling. Nonstructural proteins, particularly P, V, W, and C, interfere with the JAK-STAT signaling pathway, inhibiting the activation of IFN-stimulated genes. For instance, the V protein binds to RIG-I and MDA5, key sensors of viral RNA, preventing the induction of an antiviral state. The W protein further blocks the TLR3 and RLR signaling pathways, reducing the host’s ability to produce interferons and other cytokines essential for mounting an immune response. 

Vaccine

Recent vaccine development for Nipah virus includes promising candidates such as the ChAdOx1 NiV (adenovirus-based vaccine) and rVSV-Nipah (vesicular stomatitis virus vector-based). Both vaccines have shown efficacy in preclinical animal trials, offering protection against Nipah virus infection by targeting viral glycoproteins essential for entry.

Devnath, P., Wajed, S., Das, R. C., Kar, S., Islam, I., & Al Masud, H. A. (2022). The pathogenesis of Nipah virus: A review. Microbial Pathogenesis, 170, 105693.

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