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)