Porcine Immune Response To Nipah Virus

By



Acknowledgement

I would take this opportunity to thank my dissertation tutor, family and friends for their support and guidance, without which this research would not have been possible.

ABSTRACT

Emerging infectious diseases involving zoonosis have become important global health problems. The 1998 outbreak of severe febrile encephalitis among pig farmers in Malaysia caused by a newly emergent paramyxovirus, Nipah virus, is a good example. This disease has the potential to spread to other countries through infected animals and can cause considerable economic loss. The clinical presentation includes segmental myoclonus, areflexia, hypertension, and tachycardia, and histologic evidence includes endothelial damage and vasculitis of the brain and other major organs. Magnetic resonance imaging has demonstrated the presence of discrete high-signal-intensity lesions disseminated throughout the brain. Nipah virus causes syncytial formation in Vero cells and is antigenically related to Hendra virus. The Island flying fox (Pteropus hypomelanus; the fruit bat) is a likely reservoir of this virus. The outbreak in Malaysia was controlled through the culling of >1 million pigs.

Table of Contents

Acknowledgementii

ABSTRACTiii

CHAPTER 2: LITERATURE REVIEW1

Classification and Morphology2

Clinical presentation & pathological manifestations5

Epidemiology8

Clinical Features9

Histopathology10

Virologic Features10

Virus Reservoir12

General Overview of the NiV Replication Cycle12

A more objective introduction to the history of Hendra and Nipah virus follows14

Genome organization and structure16

Viral proteins and replication18

Reverse genetics23

Hendra clinical disease and diagnosis24

Nipah clinical disease and diagnosis27

Treatment30

Epidemiology30

Prevention and control33

End Notes35

CHAPTER 2: LITERATURE REVIEW

Nipah virus (NiV) is a paramyxovirus in the genus Henipavirus of the subfamily Paramyxovirinae within the family Paramyxoviridae, which is in the order Mononegavirales. The emergence of NiV and its genus counterpart Hendra virus (HeV) began in 1994. HeV causes a febrile respiratory illness in humans and animals, and was responsible for the deaths of two humans out of three infections and 17 horses in three separate incidents in Australia between 1994 and 1999. One of the two fatal human HeV cases resulted in death 11 months post-infection.

The first known human infections with NiV were detected during an outbreak of severe febrile encephalitis in peninsular Malaysia and Singapore from the fall of 1998 to the spring of 1999. A total of 276 patients (105 fatal) with viral encephalitis due to NiV disease were reported in peninsular Malaysia and Singapore, mostly among adult males who were involved in pig farming or pork production activities. More recently, NiV has been established as the cause of fatal human encephalitis in Bangladesh during the winters of 2001, 2003, 2004, 2005, and 2008 as well as in India in 2001 and 2007. Fruit-eating bats in the order Megachiroptera are a natural reservoir for NiV and HV, while humans are infected via intermediate hosts such as pigs, by exposure to infected fruit bats or material contaminated by infected bats, or by direct human-to-human transmission.

HeV and NiV cross-react antigenically, but not with any of the other 3 paramyxoviruses. Henipaviruses are the only zoonotic paramyxoviruses that are highly pathogenic in humans, but have a host range that spans five terrestrial mammalian orders, exceeding that of the morbillivirus canine distemper virus (CDV), which infects species across ...