1. Nipah Virus
The Next Plague?
Ramsha Kudia
MCB5505

2. Taxonomy Family: Paramyxoviridae Subfamily Paramyxovirinae
Human parainfluenza viruses 1 and 3, as well some of the viruses of the common cold
Subfamily Paramyxovirinae
Genus Rubulavirus
Genus Avulavirus
Mumps virus
Newcastle disease virus
Human parainfluenza viruses 2 and 4
Genus Henipavirus
Hendravirus
Subfamily Pneumovirinae
Nipahvirus
Bovine respiratory syncytial virus
Genus Morbillivirus
Measles virus
Human respiratory syncytial virus
Rinderpest virus
Genus Respirovirus
Murine pneumonia virus
Sendai virus

3. Henipavirus Only zoonotic paramyxoviruses and are highly pathogenic
Genome size 18.2 kb, about 15% larger than other family members
Biosafety level 4 because of pathogenicity, high mortality, and lack of treatment
The genus is able to infect a broad range of animal species, which is uncommon among the family
High mutation rates

4. Virion Structure Non-segmented, negative sense, single stranded RNA
Encapsulated
Polymorphic, but usually spherical or filamentous
Helical nucleocapsid

5. Viral Genome The genome contains 6 genes, which code for 9 proteins
M = matrix protein
organizes and maintains virion structure
Leader sequence at 3’ end and trailer at 5’ end
F = fusion protein
N = nucleocapsid gene
Fusion requires a neutral pH
G = glycoprotein, attachment
protects from nuclease digestion
P = phosphoprotein
bind to sialic acid on the cell surface and facilitate cell entry
binds to the N and L proteins and forms part of the RNA polymerase complex
L = Large polymerase
the P gene utilizes multiple reading frames to make different accessory proteins, which are not essential for replication, but may aid in survival
catalytic subunit of RNA dependent RNA polymerase
C protein regulates viral RNA synthesis and may be a virulence factor
The N, P, and L proteins are associated with genomic RNA
and form part of the RNA polymerase complex, while the M protein serves to
maintain the virion structure, assembling between the envelope and nucleocapsid
core. The V and W proteins appear to be virulence factors that act by blocking
activation of an interferon-inducible promoter (Park et al., 2003). The two membrane
glycoproteins are the F and G proteins. The fusion protein, F0, is originally
synthesized as an inactive precursor that requires cleavage by a host cell protease to
become active subunits F1 and F2. These subunits mediate the fusion of the virion
membrane with the plasma membrane of the host cell. The attachment protein, or
glycoprotein, G, serves to mediate the binding of the virus to a cellular receptor,
which has not yet been identified (Wang et al., 2001).

6. Replication and Transcription
Replication occurs in cytoplasm
The virus attaches to host surface receptors by G glycoprotein
Envelope fuses with plasma membrane and the ribonucleocapsid is released into the cytoplasm
viral RNA dependent RNA polymerase binds to the encapsidated genome at the leader region
The polymerase sequentially transcribes each genes by recognizing start and stop signals flanking viral genes
mRNAs are capped and polyadenylated by the L protein during synthesis
Replication starts when there is enough nucleoprotein to encapsidate the new virion
Matrix proteins line the cytoplasmic side of the plasma membrane
The ribonucleocapsid interacts with the matrix protein and buds off, obtaining its envelope from the plasma membrane

7. History The virus was first discovered in 1999 in Malaysia
There have been 12 outbreaks since then
Named after city
When the disease first appeared, people thought it was Japanese Encephalitis (JE)
Authorities spent 5 months vaccinating people against JE and killing mosquitoes, which was a waste of time
There were features that made it different from JE; for example, it infected adults more often then children
There was also a disease in pigs going around
Some believed it was related to Hendravirus
When the disease spread out of Ipoh, it was discovered the pigs were transmitting disease
After determining cause, 1,000,000 pigs were shot and buried, destroying half the country's pig market
Found that one of the original locations of the outbreak in pigs was near the forest where there were fruit bats
The farm was also surrounded by fruit trees, which offered food for bats
Pigs had been infected by bats, which caused a problem because pigs could be stopped from crossing borders, but bats could not

8. geographic distribution of Nipah virus overlaps with that of Pteropus genus of bats

9. Animal Pathology
Most pigs suffered from respiratory illness, while neurological symptoms were less common
Nipah outbreaks in pigs and other domestic animals (horses, goats, sheep, cats and dogs) were first reported during the initial Malaysian outbreak in 1999
Many pigs had no symptoms, but others developed acute feverish illness, labored breathing, and neurological symptoms such as trembling, twitching and muscle spasms
Generally, mortality was low except in young piglet
The incubation time for pigs 4-14 days
Pigs are infectious during incubation
Pigs spread disease by coughing

10. Natural Host Predominately family Pteropodidae – fruit bats
10 genera and 23 species of bats in a large part of Asia and Africa
aggregate with a density of more than 3,000 bats/m2, in population of up to several million individual animals
long distance flyers, with some species travelling up to 640 km during seasonal migration
Migratory bats have been shown to exchange novel viruses with non-migratory ones

11. Geographic distribution of seropositive bats is growing

12. Pathogenesis in Humans
Targets microvascular endothelial cells
At autopsy, microscopic evaluation revealed widespread vasculitis, endothelial cell destruction and focal perivascular necrosis in small vessels in the lung, heart, an kidney with the most severe damage observed in the vessels of the CNS
Microvasucular blood vessels of several organs exhibit syncytia or multinucleated giant endothelial cells, accompanied by vascular inflammation
Not a feature of other viral encephalides
Greatest viral load seen in the CNS

13. Symptoms Incubation 4-18 days Symptomatic to nonsymptomatic ratio 3:1
The onset of symptoms ranged from 24 hours to 1 month
Symptomatic to nonsymptomatic ratio 3:1
Some symptoms similar to influenza
Fever
Muscle pain
Headache
Pneumonia and systemic infection in rare cases
Seizures, abnormal pupillary reflexes, absent doll's eye reflex, profound tachycardia, hypertension, tremor, dysarthria
Reduced level of consciousness
Inflammation of brain
Disorientation
Coma
Encephalitis can be acute or late onset
Acute can result in relapse

14. Transmission Bat-to-pig Pig-to-many animals Pig-to-human Bat-to-human
Half-eaten fruit from bats
Pig-to-many animals
Direct contact or by aerosols
Pig-to-human
From direct contact with pigs
Bat-to-human
Humans eating fruit with bat saliva
Bat urine, feces, saliva
Human-to-human
Possibly through aerosol
Contamination with human excretions
Spread in healthcare settings

15. Diagnosis serum neutralization
enzyme-linked immunosorbent assay (ELISA)
polymerase chain reaction (PCR) assay
immunofluorescence assay
virus isolation by cell culture

16. Epidemiology
There have been outbreaks almost every year since it was discovered
Is a problem in Bangladesh

17. Outbreaks in of the Nipah Virus have seasonal pattern in South Asia
Limited geographical distribution
Transmission in Bangladesh also showed human-to- human transmission

18. Current Nipah Virus Outbreak
Bangladesh Bans Sale of Palm Sap After an Unusually Lethal Outbreak By DONALD G. McNEIL Jr. Published: March 21, 2011 Bangladesh is suffering an outbreak of deadly Nipah virus, causing the government to adopt an unusual prevention tactic: a ban on the sale of fresh palm sap. The virus, carried by bats, was identified only in It causes dangerous brain inflammation in humans and is infectious. The Bangladeshi outbreak is unusually lethal, killing 35 of the 40 people known to have been infected. The first known outbreak of Nipah virus was in Malaysia, where most victims raised or butchered pigs that were the source of infection. The pigs are believed to have rooted beneath bat colonies in trees, eating food contaminated by droppings. But the Bangladesh outbreak happened without a swine vector. Bangladeshis like drinking date palm sap, which is gathered “in a way similar to maple syrup collection,” said Dr. Jonathan H. Epstein, a veterinarian with the EcoHealth Alliance, which is helping Bangladesh track the virus. Gatherers called gachis climb high into the trees, shave the bark with machetes and hang clay pots on the trunks to collect the sap at night. Large fruit bats called Indian flying foxes are attracted and lap up the running sap, sometimes fouling the pots with their saliva, urine or feces. Many people in the tropics leave palm sap to ferment into wine — and fermentation might kill the virus. But most Bangladeshis are Muslim, and do not drink alcohol, Dr. Epstein said. The government health agency is also trying to persuade the gachis to put what he called “bamboo skirts” over the mouths of their collecting jars. “The gachis like them,” he said. “They keep the stuff pure, so they can sell it for more.”

19. Prevention and Treatment
Pig farmers should quarantine suspected animals and avoid direct contact
The virus can easily be killed with bleach or detergents like sodium hypochorite
Fruit should be washed and peeled before consumption
Boil date palm oil
Avoid contact with infected humans as it is possible to be infected by aerosols
There is no vaccine or treatment for Nipah Virus
Treatment is mostly focused on managing fever and the neurological symptoms
Ribavarin is used to treat symptoms such as nausea, vomiting, and convulsions
Vaccine is being developed
Recombinant sub-unit vaccine formulation protects against lethal Nipah virus in cats

20. Potential For Bioterrorism
Cause fear and panic
No effective treatment
Economic loss
Can spread through aerosols or food

21. References
Fong, I. W., and Ken Alibek. New and Evolving Infections of the 21st Century. New York, NY: Springer, Hsu, V. "Nipah and Hendra Viruses." Perspectives in Medical Virology 16 (2006): Knipe, David M. "Fields Virology by David M Knipe and Peter M Howley | Free EBooks Download - EBOOKEE!" Web. Apr Strauss, James H., and Ellen G. Strauss. Viruses and Human Disease. San Diego: Academic, Tabor, Edward. Emerging Viruses in Human Populations. Amsterdam: Elsevier, "ViralZone: Henipavirus." ExPASy Proteomics Server. Web. Apr < "WHO | Nipah Virus (NiV) Infection." Web. Apr < "WHO | Nipah Virus." Web. Apr < Wolf, Mike C., Oscar A. Negrete, and Benhur Lee. "Pathobiology of Henipavirus Entry: Insights into Therapeutic Strategies." Future Virology 2.3 (2007):

22. Any Questions?