Flaviviruses Flashcards
Where did faviviridae get its name from
flavus: Latin for yellow (cuz it causes yellow fever)
Dengue Hemorrhagic fever, tick borne encephalitis, West Nile virus, HCV, Zika virus
(animal swine fever and bovine viral diarrhea)
3 genera
- flavivirus: infects humans monkeys bats and birds
- pesstivirus: infects pigs, cattle ruminants (plauge)
- hepacivirus: infects humans (HCV) liver
Characteristics of Flaviviruses (5)
- mosquito/tick transmitted
- major envelope protein parallel to lipid membrane
- proteins synthesized as single poly protein
- pestivirus and hepacivirus have internal ribosomal entry site to begin protein synthesis
- assembles by budding fromER and released by exocytosis
Flaviviruses genome and structure
- Spherical nucleocapsid
- Enveloped
- Envelope glycoproteins have icosahedral symmetry
- Linear +ve sense ssRNA
- 5’ cap
- NO Poly A tail
Flaviviruses receptor preference
- interacts with many cell surface particles depending on host (only few receptors have been characterized )
- Antibody enhancement: non-neutralizing antibodies facilitate virus entry
How does Flaviviruses enter and fuse with the host
1- virus internalized via clathrin-coated pits
2- trafficked to pre-lysosomal endocytic compartment with low pH (inducing factor)
3- virus fuses with host membrane and nucleocapsid is released
** efficiency depends on the lipid composition of the membrane **
more cholesterol = more fusion
viral genome directly assembles for translation upon entry into host
Flaviviruses genes and proteins
genome translated as a single polyprotein (with 10 proteins) that then undergoes proteolytic cleavage
1 capsid proteins
2 envelope proteins
7 NS proteins (non-structural)
what is primary determinant of Flaviviruses infectivity?
efficiency of genome translation
- viral genome translates directly (+ve)
- single long ORF and single polyprotien
- cleaved into individual proteins by viral protease
Flaviviruses RNA replication
- semi-conservative
- occurs on cytoplasmic membranous web
- makes -ve sense RNA strand which acts as template for new +ve strand which then gets packaged
Flaviviruses assembly and release
- assembly and RNA replication are coupled
- core protiens interact with viral genome and make nucleocapsid precoursor
- gets envelope by budding from ER (fully formed virions in ER with rapid assembly)
-passes through secretory pathway and gets released from cell surface (buds from host cell? or lytic?)
Yellow fever (signs and symptoms)
initially asymptomatic but then fever, muscle and back and head pain, loss of appetite and nausea
- some people enter 2nd stage after 24hr after recovering from initial stage and then leads to liver and kidney failure (dark urine) and then jaundice and then 50% die after 7-10 days
primary reservoir for yellow fever
non-human primates
(human to human or primate to human transmission through intermediate mosquito vector)
Yellow fever treatment
early supportive care:
- treatment of dehydration
- treatment of co-occuring bacterial infection
- no specific antiviral
yellow fever prevention
- vaccination (single dose = life long immunity, cheap, oldest live attenuated virus)
- vector control (control mosquito population and personal protection)
Dengue Virus (the hemorrhagic flavivirus) transmission
monkeys are reservoir host
mosquitos transmit it (AGAIN)
Dengue Virus symptoms
sudden onset of generalized symptoms: skin rash, high fever, headache, retroocular pain, back pain, flushing
increase in severity overtime, can get second phase (hemorrhagic stage shock syndrome)
Dengue hemorrhagic stage/shock syndrome
increase in initial stage symptoms :
anorexia, weakness, decreased pulse, respiratory problems, rash spread to limbs, less WBC and platelet count
hemorrhagic: intestinal bleeding, vascular leaking, ogham failure (death 8-24hrs)
Dengue virus immunity
there are many serotypes
if you get one, ur protected against it for life, but u have INCREASED RISK of other serotypes
Antibody-dependant enhancement: memory B cells and T cells can bind to other serotypes and help them get into cells
Dengue virus treatment
- no antiviral :(
- management of symptoms (but not NSAID cuz it can increase bleeding)
Dengue virus prevention
- vector control (control of mosquitos and personal protection)
- vaccine?? can make it worse? but Dengvaxia
Dengvaxia
only given if you had confirmed prior infection (to prevent vaccine from making it worse)
approved by WHO for ppl 9-16 years in endemic regions
Neurotrophic Falviviruses :
Japanese Encephalitis Virus
West Nile Virus
Zika Virus
Symptoms of Japanese Encephalitis and West Nile Virus
most asymptomatic
both: headache vomiting seizures, stiff neck, confusion (JEV:fever, WNV:rash)
JEV: 30% fatality
WNV: 10% fatality
JEV has many reservoirs and can undergo amplification in
Swine
