Nipah virus is a bat-borne, zoonotic virus that causes Nipah virus infection in humans and other animals, a disease with a very high mortality rate (40-75%). Numerous disease outbreaks caused by Nipah virus have occurred in North East Africa and Southeast Asia. Nipah virus belongs to the genus Henipavirus along with the Hendra virus, which has also caused disease outbreaks.
Virology
Like other henipaviruses, the Nipah virus genome is a single (non-segmented) negative-sense, single-stranded RNA of over 18 kb, which is substantially longer than that of other paramyxoviruses. The enveloped virus particles are variable in shape, and can be filamentous or spherical; they contain a helical nucleocapsid. Six structural proteins are generated: N (nucleocapsid), P (phosphoprotein), M (matrix), F (fusion), G (glycoprotein) and L (RNA polymerase). The P open reading frame also encodes three nonstructural proteins, C, V and W.
There are two envelope glycoproteins. The G glycoprotein ectodomain assembles as a homotetramer to form the viral anti-receptor or attachment protein, which binds to the receptor on the host cell. Each strand in the ectodomain consists of four distinct regions: at the N-terminal and connecting to the viral surface is the helical stalk, followed by the beta-sandwich neck domain, the linker region and finally, at the C-terminal, four heads which contain host cell receptor binding domains. Each head consists of a beta-propeller structure with six blades. There are three unique folding patterns of the heads, resulting in a 2-up/2-down configuration where two heads are positioned distal to the virus and two heads are proximal. Due to the folding patterns and subsequent arrangement of the heads, only one of the four heads is positioned with its binding site accessible to associate with the host B2/B3 receptor. The G protein head domain is also highly antigenic, inducing head-specific antibodies in primate models. As such, it is a prime target for vaccine development as well as antibody therapy. One head-specific antibody, m102.4, has been used in compassionate use cases and has completed Phase 1 clinical trials. The F glycoprotein forms a trimer, which mediates membrane fusion.
Tropism
Ephrins B2 and B3 have been identified as the main receptors for Nipah virus. Ephrin sub-types have a complex distribution of expression throughout the body, where the B3 is noted to have particularly high expression in some forebrain sub-regions.
Evolution
The most likely origin of this virus was in 1947 (95% credible interval: 1888–1988). There are two clades of this virus—one with its origin in 1995 (95% credible interval: 1985–2002) and a second with its origin in 1985 (95% credible interval: 1971–1996). The mutation rate was estimated to be 6.5 × 10−4 substitution/site/year (95% credible interval: 2.3 × 10−4 –1.18 × 10−3), similar to other RNA viruses.
Geographic distribution
Nipah virus has been isolated from Lyle's flying fox (Pteropus lylei) in Cambodia and viral RNA found in urine and saliva from P. lylei and Horsfield's roundleaf bat (Hipposideros larvatus) in Thailand. Ineffective forms of the virus has also been isolated from environmental samples of bat urine and partially eaten fruit in Malaysia. Antibodies to henipaviruses have also been found in fruit bats in Madagascar (Pteropus rufus, Eidolon dupreanum) and Ghana (Eidolon helvum) indicating a wide geographic distribution of the viruses. No infection of humans or other species have been observed in Cambodia, Thailand or Africa as of May 2018. In September 2023, India reported at least five infections and two deaths.
Symptoms
Fever
Headache
Muscle pain (myalgia) Vomiting Sore throat
These symptoms can be followed by more serious conditions including: Dizziness Drowsiness Altered consciousness Acute encephalitis Atypical pneumonia Severe respiratory distress Seizures