20 - Vector Borne Viral Diseases Flashcards
Three families that most arboviruses causing human disease belong to
- Togaviridae (Alphavirus)
- Flaviviridae (Flavivirus)
- Bunyaviridae (Bunyavirus)
Alphaviruses and flaviviruses
- Enveloped
- Linear
- (+)ssRNA
- Spherical
- Underlying capsid
- Measure 40-70nm
Bunyaviruses
- Enveloped
- Circular
- (-)ssRNA
- Spherical
- Segmented
- 80-120nm in diameter
Alphaviruses subdivisions
Divided into those associated with polyarthritis and rash (mainly old world strains) and those associated with meningoencephalitis (mainly new world)
Old world alphavirus strains
- CHIKV
- o’nyongnyong virus
- Ross river
- Sindbis
Alphavirus replication cycle
- Virus binds to host receptor via E1 and E2 glycoproteins
- Clathrin dependent endocytosis occurs and nonstructural proteins are translated first from the full-length viral RNA, allowing assemblage of the viral replication complex.
- The structural proteins are translated from the subgenomic RNA.
- The capsid protein assembles into NCs with the full- length viral RNA.
- pE2, 6K and E1 insert into the endoplasmic reticulum membrane and transit to the host plasma membrane via the secretory pathway.
Chikungunya Virus
- 11.5kb enveloped (+) ssRNA
- Alphavirus genus, Togaviridae family
- Aedes (Ae.) mosquitos
- E1-A226V mutation in Ae albopictus leads to increased infectivity and transmissibility
- Sylvatic and urban cycles
Chikungunya pathogenesis
- Incubation period of 4 and 7 days
- Fever and severe, debilitating joint pain
- Arthralgia can last for months and disease can evolve to chronic rheumatoid arthritis
- Neurological, cardiac and GIT problems in older patients
- Meningoencephalitis in neonates
- No cure, and treatment is focused on relieving the symptoms
Ross River Virus
- (+)ssRNA, enveloped
- Alphavirus genus, Togaviridae family
- Aus endemic
Ross River Transmission
- Transmission is maintained in mosquito mammal cycle involving macropods and other marsupials.
- Rodents and horses act as amplifier hosts
- Spread by different types of mosquitoes with Aedes vigilax most common
Ross River Fever
- Most infections asymptomatic
- Causes acute febrile illness for 2-5 days followed by prolonged arthralgic disease that may last for many months
- ““Epidemic polyarthritis”
Barmah Forrest Virus
- (+) ssRNA,enveloped
- Alphavirus genus, Togaviridae family
- Second most prevalent arbovirus disease in Australia
- Clinical presentation closely mimics that of RRV
- Arthritis is more common in RRV, rash more common in BFV infection
- Similar to RRV, transmission is maintained in mosquito-mammalian cycle
- Aedes vigilax
Flaviviruses structure
- (+)ssRNA, enveloped virus
- Assembled using three viral structural proteins, a host lipid envelope and the viral genomic RNA.
Three viral structural proteins of Flaviviruses
C, prM and E
E protein
A three-domain structure (referred to as domains E-DI, E-DII and E-DIII) tethered to the viral membrane and is antigenic determinant
Flavivirus replication cycle
- Virions are internalized by clathrin-dependent mechanisms that usurp host factors involved in the uptake of large macromolecules
- Viral RNA replication occurs on membranes of the host reorganized through the actions of the nonstructural proteins.
- These virus-induced membrane structures spatially coordinate viral genomic RNA replication and virion morphogenesis, and shield replication products from host innate immune sensors.
- Virus particles assemble at and bud into the ER and traffic out of the cell
Flavivirus genome
Genomic RNA encodes a single open reading frame flanked by highly structured untranslated regions (UTR) that coordinate viral translation, replication and regulation of the innate immune response.
Examples of flaviviruses
- Yellow fever
- Dengue
- Japanese encephalitis
- Murrary valley encephalitis
- West Nile
Different disease syndromes of flavivirus
- Neurotropic disease
- Visceral disease
- Congenital disease
Neurotrophic disease
- Encephalitis
- Cognitive impairment
- Flaccid paralysis
Congenital disease
- Microcephaly
- Placental insufficiency
Visceral disease
- Hepatitis
- Vascular leakage
- Haemorrhage and bleeding
- Shock syndrome
Dengue
- (+) ssRNA, enveloped virus Genus Flavivirus, Family Flaviviridae
- Four distinct serotypes: DENV-1 – DENV-4
- RNA genome, exits as quasispecies and as clades or genotypes
Peak dengue viraemia
Correlates with high fever and coincides with the initiation of IgM and IgG production, which promote clearance of virus infection.