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MIMM 465 (7)
Lecture 4

Lecture 4.docx

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Department
Microbiology and Immun (Sci)
Course Code
MIMM 465
Professor
Edith Zorychta

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Description
Lecture 4 Henipavirus - A genus of the family Paramyxoviridae, order Mononegavirales - Contains 3 established species: 1. Hendra virus 2. Nipah virus 3. Cedar virus - Example of emergent virus diseases  HIV and SARS was also an emergent virus disease  Cause serious disease and not have been known in people In Brisbane, Australia… - The center of Australian horse racing - There are many horse farms - In August 1994, Mackay, Australia (1,000km north of Brisbane)  Two horses developed frothy nasal discharge and subsequently DIED  Their owner, Mark Preston, assisted in necropsies (autopsies) of the horses  Within 3 weeks the owner was admitted with meningitis  initially recovered 14 months lather developed neurologic signs and died  This outbreak wasn‟t initially diagnosed as being caused by any specific virus - In September 1994 Hendra, a suburb of Brisbane in Queensland, Australia  The index case, a mare was housed with 19 other horses after falling ill, and it died 2 days later  Subsequently, all of the horses became ill, with 13 dying  The head trainer, Vic Rail, and a stable hand were involved in nursing the index case  BOTH fell ill with influenza-like illness w/in 1 week of the 1 horse‟s death  The stable hand recovered while Mr. Rail died of respiratory and renal failure  The source of the virus was most likely frothy nasal discharge from the nose of the index case - The 6 surviving horses were quarantined  Body fluid samples taken  Then the surviving horses were euthanized as a way of preventing relapsing infection and possible further transmission Samples were transferred to the center for disease control and prevention (CDC) - Level 4 laboratory - They 1 tried to identify the virus by multiplex PCR Multiplex PCR - Four or more different are ran in a single reaction, each of them giving you a specific band - You are doing a PCR for a likely virus candidate, such as coronavirus, influenza, etc in a rapid fashion - They did this for ~38 viruses and came out COMPLETELY negative Rapid ID of emerging infectious agents using PCR and electrospray ionization mass spectrometry - To identify product bands - Automated PCR/ESI-MS biosensor - Key modules include  Amplicon purification (desalting)  Plate stackers – so you could run different plates (each plate has a well that you could run a particular PCR rxn) – can run 64 wells in each of the plate  Automated sample injection and mass spectrometry analysis - Precise molecular weight determinations of amplicons yield unambiguous base compositions that are used to uniquely “fingerprint” each pathogen - They take primers that are homologous to the most conserved regions of every known virus group & multiple conserved regions  To identify new viruses - The automated system is capable of analyzing more than 1,500 PCR rxns in 24h - They had to run 12,000 PCR rxns before nailing down the new virus - W/in 6 days the CDC IDed the causative agent in Hendra, Australia as a hitherto unknown Paramyxovirus  This was named Hendra virus  Like a typical Paramyxovirus, it has a plasma membrane with surface glycoprotein spikes in it, has nucleocapsid, and has long single stranded (15,000 nts) RNA that is encapsidated in a (-) sense  The virus has 2 surface proteins, F (fusion) protein and G (attachment) protein - G protein binds to host cell receptor  Matrix (M) protein underlies the plasma membrane, associated with genome ssRNA  Nucleocapsid transcriptase complex that consists of L (large polymerase) protein, N (nucleocapsid) protein and P (phospho) protein  Gene map of Paramyxovirus - Starting from the 3‟ end of the (-) strand of genome RNA, there are 6 cistrons, encoding the 6 known proteins that are encoded by the virus The Hendra virus G protein was expressed in a yeast vector - They removed the carboxy-terminal anchor region and the yeast secreted soluble G protein (which was glycosylated by the yeast) into the tissue culture medium that the yeast was grown in - The resulting large amount of secreted G protein were purified by chromatography  were used as antigen to set up an ELISA assay for specific serum antibody against Hendra virus  Started to look for WHERE the Hendra virus came from - Emerging virus come from either: isolate human populations that suddenly came into contact with rest of humanity (not common) OR from animal reservoir that suddenly came into contact with human - The ELISA was used to screen 46 species of wildlife in the vicinity of Hendra, Australia  The only seropositive culprit came out to be a fox-headed fruit bat! Fox-headed fruit bat - BIG – wings spread about 3feet - Have faces that look like foxes and body size is close to foxes - Fly BOTH at day and night - Hang from trees - QUITE a lot of them in North-eastern Australia (near Hendra) - Eat fruits and more commonly drink flower nectar like insects  Originally called vampire bats, b/c during the night time, you could hear the sucking noises of the plant nectars - BAT saliva carries viruses As of December 2012, 39 outbreaks of Hendra virus have occurred in Australia - ALL in North-eastern Australia - All involving infection of horses - 80 horses have died or been euthanized - FOUR of these outbreaks have spread to humans as a result of direct contact with infected horses - TEN humans have been infected AND four have died – 40% of death rate - So far no documented human to human transmission of Hendra virus BUT only horse to human - Case fatality rate in human is 40% in human and 75% in horses - ALL outbreak sites had been w/in the distribution of at least two of the four mainland flying-foxes (fruit bats) species - The timing of incidents indicates a seasonal pattern of outbreaks, possibly related to the breeding cycle of the flying- foxes  These species typically give birth b/w April and May and outbreaks occur June through September In November 2012, a vaccine became available for horses. - The vaccine is a subunit vaccine composed of a soluble version of the G surface antigen on Hendra virus and has been successful in ferret models - Breaking the transmission cycle from flying foxes to horses prevents it from passing to humans - Currently, there aren‟t many human cases to develop a HUMAN vaccine In April 1999, outbreak of neurological and respiratory disease on pig farms in lower peninsula of Malaysia - 257 human cases, including 105 human deaths and the culling of one million pigs - The outbreak was originally mistaken for encephalitis - Physicians in the area noted that persons who had been vaccinated against JE were not protected, and the number of cases among adults was unusual for JE encephalitis (mosquito born infection) - It was mainly the people of pig farms, who became sick - Samples sent to reference labs identified a new virus named Nipah virus – closely related to Hendra virus st - “Nipah” refers to the place, Kampung Baru Sungai Nipah in Negeri Sembilan State, Malaysia, where the virus was 1 isolated - Symptoms – primarily encephalitic (brain infection) in humans & respiratory, nasal secretions and pneumonia in pigs  Later outbreaks have caused respiratory illness in humans - In humans, Nipah presents as fever, headache and drowsiness  Cough, abdominal pain, nausea, vomiting, weakness, problems with swallowing and blurred vision are common  About a quarter of the patients have seizures due to cerebral infection  60% become comatose and need mechanical ventilation Cycle where pigs eat feed that are contaminated by flying-fox saliva  pigs get sick  humans catch the infection from pind - But there is a 2 mode of transmission of Nipah virus to humans  In SE Asia, people harvest the sap of date palm trees in the way QC ppl harvest maple sap  Slightly sweet liquid that can be drunken directly and can be concentrated into a syrup by boiling  Can be fermented into alcoholic beverage  A hole is made on the tree and a pot is hung under the hole to collect the dripping syrup  Fox-bats like to drink the sweet secretion  bats leak at the collected syrup  syrup contaminated with flying- fox saliva  outbreaks caused by direction transmission from the flying-fox bat to human Outbreaks - Henipavirus outbreaks: Hendra virus in North-eastern Australia & Nipah virus in Malaysia, Bangladesh and India - Distribution of Henipavirus flying fox reservoirs  4 species of fruit-bats – 2 of them in more southern range and 2 others in Malaysia, Bangladesh and India Simple cycle of the Henipavirus - Reservoir host bats infect pigs/horses  pigs/horses infect human - OR reservoir host bypass the spillover hosts and directly to the human  In case of Malaysia 8 more outbreaks of Nipah virus have occurred since 1998 - ALL w/in Bangladesh and neighbouring parts of India - The outbreak sites lie w/in the range of fox bats - As with Hendra virus, the timing of the outbreaks indicates the seasonal effect Family Paramyxoviridae (DON’T HAVE TO MEMORIZE) - Subfamily Paramyxovirinae  Genus Aquaparamyxovirus (type species Atlantic salmon paramyxovirus)  Genus Avulavirus (type species Newcastle disease virus of fowl)  Genus Henipavirus (type species Hendravirus; others include Nipahvirus)  Genus Morbillivirus (type species Measles virus; others include Rinderpest virus, Canine distemper virus)  Genus Respirovirus (type species Human parainfluenza viruses 1 and 3) as well as some of the viruses of the common cold)  Genus Rubulavirus
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