noro and flavivirus Flashcards
hoe do enteric viruses gain entry to the body
*surface coat of glycoproteins and glycolipid and an overlying mucous layer
- viruses (adenovirus/Norwalk calicivirus) penetrate this layer
* lymphoid follicles point of entry for some
- M cells ingest and deliver antigens to underlying lymphoid tissue by
transcytosis
immune defence agains enteric viruses
- Primary natural defence: innate response
- The adaptive response does not influence virus growth for several days
- But adaptive response is essential for final clearance of virus and providing memory defense
- Acute infections in immuno-compromised individuals can be disastrous
norovirus: genome structure
+ssRNA non-enveloped that causes acute gastroenteritis. appears to be the most common cause of viral gastroenteritis. encodes for a single capsid protein
why is norovirus seen as “the perfect human pathogens”?
- highly contagious,
- rapidly and prolifically shed,
- constantly evolving,
- evoking limited immunity, and
- only moderately virulent, allowing most of those infected to fully recover, thereby maintaining a
large susceptible pool of hosts.
norovirus epidimiology
- Worldwide distribution
- 10% of the population infected every year
- ~700 million infections world-wide
- 2-3 million cases/year in Australia
- 200,000 deaths/year in developing countries
- Major cause of foodborne outbreaks of GE
- Most people have had infections by age 4 years
(by seroprevalence studies) - Individuals with a mutation in the HBGA Fuc2 gene are less susceptible to infection
- Source usually is contaminated food and water
(seafood-oyster and shellfish etc.)
norovirus food transmission
-primary transmission: by contamination of foods in raw material stage before harvesting and application of contaminated water on crops
- Secondary transmission occurs during processing, storage, distribution and preparation. can come from infected food handlers and contaminated surfaces or equipment
detection of norovirus
specimen: stool, vomitus, environmental swabs. not yet on foods
immune electron microscopy
most common to do PCR
serology done for epidemiology reasons
only recently can be grown in culture
norovirus prevention and treatment
no medicine really, symptoms resolve themselves after a day or two. no vaccine yet but is an active field of research
arbovirus
transmitted by an infected blood sucking arthropod
replicates in arthropod vector AND host which is a challenge for virus
maintained within vertebrate host
humans are not primary host but incidental host. exceptions to this is yellow fever and dengue where humans are the main host
most belongs to toga, flavi, reo and bunya which are all RNA viruses
dead end infections
frequent outcome of cross species infection
often host is killed so quickly so there is little to no transmission to others or the host cannot transmit to others of the same species
dengue can actually transmit back to the mosquito from human because of high viremia
geographical distribution of the vector determines where the infection will exist
south america has a lot of viruses
flavivirus features
hepatit C, dengue and zika
ss+RNA
enveloped
exists in an immature and mature form
flavivirus life cycle
entry into cell via clathrin mediated endocytosis
fusion with endosome
uncoating and release of viral rna and immediate translation via host endoplasmatic reticulum
genome replication in virally induced replication complexes
translocation via secretory pathways and release via exocytosis
used antibodies and EM to see viral protease NS3 of flavivirus, found an intermediate compartment for replication
forms vesicle packages within ER
flavivirus transmission
exists within different cycles
most common is enzootic cycle: virus in mosquitoes, has reservoir in small mammal and infects humans. humans are considered a dead end host
epizootic cycle: reservoir in domesticated animals such as pigs. replicates in those animals effectively and then transmits to mosquito and infects humans
urban epidemic cycle: mosquito only feed on us. dengue and yellow fever. zika can be spread via sexual transission which is the first time we saw an arbovirus spread between humans and not be a dead end host
flaviviruses diagnosis and symptoms
flaviviruses can be hard to diagnose because the symptoms are similar to other infections. can be a neurotropic, visceral and congenital disease and cause hepatitis, cognitive impairment etc depending on virus. zika can infect unborn child
denguevirus: why is a secondary infection more severe?
a primary dengue infection can be either asymptomatic or classic virus symptoms. there is a risk for haemorrhagic fever that is significantly increased with a secondary infection. haemorrhagic fever causes internal bleeding that leads to fatal dengue shock syndrome. incidence with primary infection is 1 in 14 000 and in secondary its 1 in 90. there are 4 different serotypes of dengue that are crossreactive meaning the antibodies recognizes the other serotypes as well in a secondary infection. the antibodies will bind to the virus but fail to neutralize it and instead facilitate uptake into monocytes which is the tropic cell dengue is looking for. this causes th virus to be able to replicate to high levels within monocytes. newborns can get antibodies from placenta, causing a secondary infection response when infected. elevated levels of cytokines and inflammatory mediators is seen which is thought to promote capillary permeability but the exact mechanasim leading up to heamotthagic fever is unclear.n loss of essential coagulatino proteins probably plays a major role in disease as well.
