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.
Secondary heterologous DENV infection
Period of viraemia is shorter, due to cross-reactive immunity, including pre-existing antibodies
Dengue fever
- Flue like illness
- Hypovolemic shock (severe dengue)
- Severe disease frequently occurs in the setting of secondary infection with a heterologous serotype
- Immunity to infections with one serotype is lifelong
Murray Valley Encephalitis Virus
- (+) ssRNA, enveloped virus
- Genus Flavivirus, Family Flaviviridae
- Member of the JEV serogroup
- Maintained in enzootic foci in water birds
- Spread of MVEV outside enzootic foci is likely due to rainfall and flooding that allowed movement of infected water birds to previously arid environments
MVEV clinical manifestations
- Commonly subclinical infection with fever or headache
- Can cause encephalitis (altered mental status, convulsions and coma)
- 4 week incubation
West Nile Virus
- (+) ssRNA, enveloped virus
- Genus Flavivirus, Family Flaviviridae
- Humans horses and mammals are dead end hosts
- Cycles between mosquitoes (culex species) and birds
West Nile Virus clinical manifestations
- Most infections asymptomatic
- Symptoms include headache, body aches, joint pains, vomiting, diarrhoea or rash
- Severe disease causes encephalitis
- No vaccine or antivirals
Bunyaviruses
- Spherical, enveloped particles 90 to 100 nm in diameter
- (-) ssRNA, segmented genome, enveloped virus
- Comprised of only four structural proteins.
- Genomes are divided into three negative single-stranded RNA segments, which are hidden by
multiple copies of N. - Genetic reassortment can occur during infection because the RNA is segmented
Structural proteins of bunyaviruses
- Two of them are envelope
glycoproteins (Gc and Gn), - The other two are internal proteins, the nucleocapsid protein or nucleoprotein (N) and the L protein (the viral RNA polymerase).
4 genera of Bunyaviruses that are human pathogens
- Orthobunyavirus
- Nairovirus
- Phlebovirus
- Hantavirus
- All but Hentaviruses are arboviruses
Crimean Congo haemorrhagic fever virus
- (-) ssRNA, segmented genome, enveloped virus
- Genus Nairovirus, Family Bunyaviridae
- Maintained in Hyalomma ticks
- Transmitted to humans by close contact, tick bites, or contact with infected animals immediately after slaughter
Crimean Congo haemorrhagic fever virus infecion
- Incubation period following tickbite 1-3 days to 9days
- Following contact with blood or tissues 5-6 days to 13 days.
- Acute febrile illness which may be followed by abdominal pain, petechial rash and haemorrhagic phenomena
- 40% mortality rate
Rift Valley Fever Virus
- (-) ssRNA, segmented genome, enveloped virus
- Genus Phlebovirus, Family Bunyavirales
- Maintained in livestock (mosquito cycle)
- Transmitted by close contact with infected animals immediately after slaughter
Rift Valley Fever Virus Infections
- Incubation period of 2-6 days
- Majority asymptomatic
- Typically, patients recover within two days to one week after symptom onset.
- Small percentage (8-10%) of people infected with RVFV develop much more severe symptoms
