Arboviruses: Togaviridae & Flaviviridae Flashcards
Arboviruses
arthropod borne viruses
viruses are biologically transmitted between susceptible vertebrate hosts by blood feeding arthropods (insects, ticks) or through transovarian or venerial transmission in arthropods
vector
an organism that transmits a disease agent from one animal or plant to another
Arbovirus Transmission Cycle
virus arthropod vector host virus
mosquito borne virus transmission cycle
mosquito host (bird) --> host (horse) intrinsic incubation period extrinsic incubation period
intrinsic incubation period
time taken by an organism to complete its development in the definitive host
extrinsic incubation period
interval between the acquisition of an infectious agent by a vector and the vectors to other susceptible vertebrates
West Nile Virus Transmission Cycle
mosquito (vector) bird reservoir host –> human & horse (incidental infection)
enzootic cycle
Types of Arbovirus Transmission by Mosquitos
Horizontal Transmission:
- vector to vertebrate
- vector to vector (venereal)
Vertical Transmission (parent passes virus to offspring)
- transovarial (ovarian follicles are permissive to virus replication)
- transovum (virus transferred to egg as the egg passes through oviduct)
Family: Togaviridae
- genome: linear, ssRNA (+)
- icosahedral capsid
- surrounded by an envelope “toga” (lipids derived from host cell membrane; glycoprotein spikes protruding from surface of virion= unique antigenic determinants for alpha viruses)
- spherical
Genera of Togaviridae
Alphavirus: Sindbis Eastern equine encephalitis Western equine encephalitis Venezuelan equine encephalitis Ross River O’nyong’nyong Semliki Forest Chikungunya
Rubivirus:
Rubella virus
Alphavirus
genera of togaviridae
vector= mosquitos
vertebrate reservoir hosts= wild birds, rodents, wild primates, humans
Arbovirus nomenclature
may be based on endemic areas and symptoms induced by virus infection
Alphavirus & Rubivirus- Structure & Replication
Genome encodes early (non-structural) and late (structural) proteins
Replication is in the cytoplasm
Viruses bud at the plasma membrane
Alphavirus & Rubivirus- Attachment & Replication
Virus entry into cells by receptor-mediated endocytosis
(each virus has a different host range depending on glycoprotein affinity to host cell receptors)
Viral envelope then fuses with the membrane of the endosome upon acidification of the vesicle to release the capsid and genome into the cytoplasm
Alphavirus & Rubivirus- Synthesis of Early Proteins
In cytoplasm, viral RNA binds to the ribosome as the messenger RNA
Initially, the genome is translated (2/3rds of genome) into a polyprotein which is cleaved by proteases into four nonstructural early proteins (NSP 1-4)
These proteins include a protease activity and an RNA-dependent RNA polymerase
Alphavirus & Rubivirus- Synthesis of Late Proteins
A full-length (-) sense RNA (42S) is transcribed by RNA polymerase which acts as a template for more viral genome
–Many positive (+) RNA strands formed from the template
A smaller (26S) RNA is transcribed from this template
- -This RNA encodes the capsid and envelope proteins
- -Capsid proteins formed by protease cleavage of the polyprotein produced from the 26S RNA (translated 1st and cleaved)
Alphavirus & Rubivirus- Assembly
Capsid proteins associate with genomic RNA after synthesized and bind them to areas of the cell membrane which express the viral glycoproteins (E1, E2, E3)
Glycoproteins associate with the capsid
Viruses released from host cell via budding
Alphavirus & Rubivirus Replication Cycle
1-receptor mediated endocytosis
2-endosome acidification
3-translation of RNA genome (i.e., protein synthesis)
4-proteolytic cleavage
5-replication of genome - + -
6-subgenome
7-protein synthesis membrane insertion
8-assembly
9-budding
Clinical Syndromes of Alphaviruses
Usually low grade and mild (fever, chills, rash, aches)
Flu-like symptoms coincide with systemic infection during the initial viremia (3 to 10 days)
(replication in the reticuloendothelial system–component of immune system)
May progress to encephalitis (inflammation of the brain) in humans but usually resolve without sequelae (after effect of disease)
Alphavirus: “Encephalitis Illness”
Eastern equine encephalitis virus=
- Culiseta melanura, Culex spp., Aedes spp. (mosquitos)
- Amplification hosts: wild birds
- 5% of infections result in encephalitis (33% mortality and brain damage in most survivors)
Venezuelan equine encephalitis virus=
- Culex spp. (mosquitos)
- Amplification hosts: rodents
- emerging pathogen of humans/equines in neotropics (outbreaks may involve thousands of equine/human cases, spread over large regions, lasting several years)
Western equine encephalitis virus=
- Culex spp. (mosquitos)
- Amplification hosts: wild birds
- 639 confirmed cases in U.S. since 1964
incidental infection: humans & horses
Alphavirus: “Febrile Illness”
O’nyong-nyong virus (ONYV)=
-Means “weakening of the joints”
-Anopheles spp. (mosquito)
-Hosts: humans
-Fever, rash, polyarthritis, eye pain, chest pain,
inflammation of lymph nodes, lethargy (no mortality)
Chikungunya virus (CHIKV)=
-Means “that which bends up”
-Aedes spp. (mosquito)
- Active during day and anthropophilic
-Hosts: humans (reservoir host)
- Urban transmission cycle
(Human-mosquito-human transmission)
-Fever (2-5 d), joint pains (weeks to months), rash, headache, muscle pain, nausea, fatigue
–> A single mutation (E1-A226V) in CHIKV resulted in increased fitness of CHIKV in A. albopictus mosquitoes with respect to:
midgut infectivity
dissemination to the salivary glands
transmission to vertebrate hosts
Rubivirus
genera of togaviridae
Not transmitted by insect vectors (contagious)
Shares the structural properties and mode of replication as other togaviruses
Rubella is transmitted by airborne droplets (coughing/sneezing)
Rarely causes serious illness in infants and young children, but infection in pregnant women can cause unborn babies to have serious congenital defects or death
Children infected with rubella virus may have;
Incubation period, 14-21 days
rash (starts on face and spreads to neck, chest, arms, legs) lasting ≈3 days
swelling of lymph nodes
fever
Adult infection (may be more severe, arthralgia)
Rubella infection during pregnancy
may lead to miscarriage, stillbirth, premature delivery, and birth defects
Risk is highest during initial 12 weeks of pregnancy
Birth defects include deafness, cataracts, heart defects, mental retardation (called Congenital Rubella Syndrome, CRS)
Congenital Rubella Syndrome (CRS)
deafness, cataracts, heart defects, mental retardation
