Nipah Virus

INTRODUCTION

• Nipah virus (NiV) infection is a newly emerging zoonosis that causes severe disease in both animals and humans.

CLASSIFICATION

• Group:  Group V (−)ssRNA)
• Order: Mononegavirales
• Family: Paramyxoviridae
• Genus: Henipavirus

 NATURAL HOST

• Fruit bats of the Pteropodidae Family, Pteropus genus. 

OUTBREAK

• NiV was first identified during an outbreak of disease that took place in Kampung Sungai Nipah, Malaysia in 1998.
• On this occasion, pigs were the intermediate hosts.
• However, in subsequent NiV outbreaks, there were no intermediate hosts.
• In 2001 West Bengal.
• In Bangladesh in 2004, humans became infected with NiV as a result of consuming date palm sap that had been contaminated by infected fruit bats
• In May 2018 Kerala, infection in humans with the NiV reported with the same cause as noticed in the year2004, in Bangladesh.   

TRANSMISSION

• Infected bats shed virus in their excretion and secretions such as saliva, urine, semen and excreta .
• The NiV is highly contagious among pigs, spread by coughing.
• Humans contract infection via direct contact with infected pigs.
• Human-to-human transmission has also been documented, including in a hospital setting in India

BIOSAFETY LEVEL

• The Center of Disease Control (CDC) has declared it a biosafety level 4 agent.
• This is the highest biosafety level category, home to agents which can be distributed via aerosol transmission and have no treatment or vaccine.
• The availability, simplicity to produce and disperse, and high mortality rate of the Nipah virus make it possible for it to be used as a weapon of biological warfare. 

MORPHOLOGY 

• Pleomorphic
• Shape is varied, and traditionally 40 to 600 nm.
• Core of a virion contains a linear ribonucleoprotein comprising of negative-sense single-stranded RNA
• Also present in the RNP are three critically important proteins
• Nucleocapsid proteins are tightly bound to the various nucleotides of the RNA strand

1. N protein is the most abundant protein present and necessary for capsid structure.
2. Phosphoproteins
3. Large polymerase proteins are also bound to the RNA

• The virion is enveloped by a traditional lipid bilayer but “spiked” with fusion  and receptor-binding glycoproteins
• The fusion proteins are responsible for fusing the viral membrane to the host membrane triggering the release of the contents of the virion.
• The receptor-binding glycoproteins are extremely specific and bind only to Ephrin B2 (EFNB2) surface proteins
•  Specifically, NiV has been found to alternatively bind to EFB3 as well.
• The EFNB2 surface proteins are highly conserved across the mammalian lineage 
• On the underside of the lipid bilayer matrix proteins (M) are present for structural support and regulating the budding process.
• Other proteins, C, V, and W, are also present in the cytoplasm and involved in regulation of transcription and

VIRULENCE

• P gene encod for the C, V, and W proteins which play a role in the virulence of NiV

PATHOGENESIS

• Virion binds and fuses to the surface of a host cell via the F and G proteins.
• The lipid bi-layers are then melted and the viral nucleocapsid is released into the host cell.
• The negative sense viral RNA is transcribed to mRNA which acts as a template for more negative sense viral RNA.
• The viral RNA is used to make the necessary proteins (N,P,M,F,G,L,C,V,W) which congregate near the cell membrane.
• Once all the necessary proteins are assembled a new viral cell will bud off and infect other hosts
• The new viral cells are able to fuse together and create a huge multinucleated cell called syncytia
• A major difference between the reproduction of paramyxoviruses and influenza is  that paramyxoviruses are strictly reproduced in the cytoplasm

CLINICAL MANIFESTATIONS

Incubation Period

• In Pigs:  varies but is usually short between 2 and 10 days.
• Human: 2 days to a month

Organ affected

• The Nipah virus primarily attacks the respiratory system, which is supported by the finding of high concentrations of viral antigens  in the respiratory tract and lung epithelium 
• Unlike Nipah virus infection in pigs, human infection is particularly encephalitic in nature.

Sign and Symptoms

• Fever
• Headache and drowsiness
• Confusion, disorientation
• Encephalitis
• Vasculitis
• Neurological deficits due to necrosis, thrombosis, and ischemia.
• The cerebrospinal fluid is also heavily impacted by an increase of proteins and dead cells present.
• The heavy encephalitic nature of NiV infection in humans also results in brain lesions, often times causing a relapse of encephalitis in patients who had recovered from NiV infection.
• Humans infected with NiV have a much higher fatality rate ranging from 40% to 75% depending on the location of the infection 

DETECTION

• Isolation from tissue samples.
• In all species, NiV can be detected and isolated from the kidneys, cerebrospinal fluid, and the liver.
• Polymerase chain reaction, enzyme-linked immunosorbent, and immunofluorescence assays are also viable detection strategies 

VACCINATION

• Currently, there are no vaccines or drugs which can cure or treat a NiV infection.

TREATMENT

• The primary approach is to treat the symptoms as best as possible in hope to control the infection.
• Patient is kept in ICU.