Replication occurs in the cytoplasm (20-30 hrs)
Entire virus genome is translated as a single polyproteinwhich is then cleaved into the mature proteins
Structural proteins: encoded at the 5’ end
Nonstructural proteins (e.g., NS-1 and RNA-dependent RNA polymerase) are encoded in the 3’ two-thirds
Complementary negative strand RNA is synthesized byNS proteins and then is used as a template for genomicprogeny RNA synthesis
Assembly occurs characteristically into cytoplasmicvacuoles (in association with Golgi or smoothmembranes)
Release occurs when cell lyses
FLAVIVIRUS PATHOGENESIS AND CLINICALMANIFESTATIONS
Flaviviruses vary widely in their pathogenic potential andmechanisms for producing human disease
It is useful to consider them in three major categories
Those associated primarily with the encephalitisSyndrome (prototype: St. Louis encephalitis)
Those associated with fever-arthralgia-rash(prototype: dengue fever), or
with hemorrhagic fever (prototype: yellow fever)
Human infection initiated by deposition of virus throughthe skin via the saliva of an infected arthropod
Replicates locally & in regional lymph nodes
Most human infections with St. Louis enceph (SLE) andJapanese enceph (JE) viruses, there is either no apparentdisease or a nonspecific febrile illness with headache
Infection resolves, and lasting immunity is produced
CNS lesions may develop: aseptic meningitis orencephalitis
In the great majority of flavivirus infections, virus iscleared by the immune system
However, persistence in neurological tissue hasbeen noted with tick-borne encephalitis viruses, andrecent reports of recurrent encephalitic bouts inchildren have been associated with JE virusrecovery from peripheral blood mononuclear cells
Lasting protection is generally restricted to the sameflavivirus, and is associated with neutralizing antibodies
Anthropod-borne viruses (arboviruses) WHO definition: “Viruses maintained in nature principally throughbiological transmission between susceptible vertebratehosts by haematophagus arthropods.”
Arboviruses belong to three families1.Togaviruses
e.g. EEE, WEE, and VEE2.Bunyaviruses- e.g. Sandfly Fever, Rift Valley Fever, Crimean-Congo Haemorrhagic Fever3.Flaviviruses
e.g. Yellow Fever, Dengue, JapanesesEncephalitis
e.g. Dengue, Urban yellow fever
Reservoir may be in either man or arthropod vector
In the latter transovarial transmission may takeplace
e.g. Japanese encephalitis, Jungle yellow fever
Reservoir is in an animal
Virus is maintained in nature in a transmission cycleinvolving the arthropod vector and animal. Manbecomes infected incidentally.
Both cycles may be seen with some arboviruses such asyellow fever
Japanese encephalitis, dengue, yellow fever, St.Louis encephalitis
Various tick-borne encephalitides etc.
In many cases, the actual reservoir is not known. Thefollowing animals are implicated as reservoirs
Birds: Japanese encephalitis, St. Louis encephalitis
Pigs: Japanese encephalitis
Monkeys: Yellow Fever
Rodents: Russian Spring-Summer encephalitis
Fever and rash
This is usually a non-specific illness resembling anumber of other viral illnesses such as influenza,rubella, and enterovirus infections. The patientsmay go on to develop encephalitis or haemorrhagicfever
St. Louis encephalitis, Japanese encephalitis
e.g, Yellow fever, dengue
Serology – usually used to make a diagnosis of arbovirusinfections
Culture – a number of cell lines may be used, includingmosquito cell lines. However, it is rarely carried out sincemany of the pathogens are group 3 or 4 pathogens
Direct detection tests – e.g. detection of antigen andnucleic acids are available but again there are safetyissues
Surveillance – of disease and vector
Control of vector – pesticides, elimination of breedinggrounds
Personal protection – screening of houses, bed nets,insect repellants
Vaccination – available for a number of arborealinfections e.g. Yellow fever, Japanese encephalitis,Russian tick-borne encephalitis
First discovered and originally restricted to Japan. Nowlarge scale epidemics occur in China, India and otherparts of Asia.
Flavivirus, transmitted by culex mosquitoes
The virus is maintained in nature in a transmission cycleinvolving mosquitoes, birds and pigs.
Most human infections are subclinical, the unapparent toclinical cases is 300/1.
In clinical cases, a life-threatening encephalitis occurs.
The disease is usually diagnosed by serology. No specifictherapy is available.
Since culex has a flight range of 20km, all local controlmeasures will fail. An effective vaccine is available.