Yellow Fever and Zika Details

Walter Reed

Proved that yellow fever was a mosquito-borne infection and opened the doors to the discovery of other vector-born etiologies

Yellow fever Sx

Most are asymptomatic

Mild disease: sudden onset of fever and headache, myalgia, lower backache, and low-grade proteinuria

Severe disease: High fever, vomiting, abdominal pain, dehydration, foul breath, jaundice, bleeding in gums and nose, and severe pain in limbs, loins, and back (viremic phase)

Yellow Fever life-threatening phase

Occurs after the viremic phase where after 24 hours of improvement turn to rapid deterioration that leads to ultimate recovery or death

YFV infects

Macrophages and DCs

They spread to other tissues via the two cells above 

Kupfer cells

Macrophage-like cells in the liver

Infection by yellow fever virus is responsible for jaundice (a product of liver damage)

Yellow fever causes necrotic areas in. . .

the spleen, lymph nodes, tonsils, and Pyre’s patches

Councilman bodies

apoptotic hepatocytes that stain strongly with Eosin

Observed in liver biopsies of yellow fever patients

Flavivirus

Group of viruses abroviruses, Baltimore type IV, enveloped.

Causes several illnesses including yellow fever, Dengue, Tick-borne encephalitis, St. Louis Encephalitis, West Nile Virus, and Japanese encephalitis

Flavivirus structural proteins

E protein, M protein, and C protein

E protein

Helps fuse viral envelope to host membrane

M protein

Associates with viral envelope (membrane)

C protein

Forms protective coat (capsid) around genome

Flaviviruses replicate in ________ preventing immune response 

ER membrane

Flaviviruses immune response evasion mechanisms

ER-derived vesicles are inaccessible to pattern recognition receptors

Viral NS1 proteins prevents nuclear translocation of IRF-3, preventing type I interferon production

NS2 a protein interferes with IFN-beta gene transcription

NS2A, NS4, and NS4b interfere with JAK activity, limiting STAT activation

NS5 binds to the IFN receptor to prevent activation of JAK1 and TYK2

Flaviviruses attach to _______ in mosquitoes

lectin DC-SIGN

Infected DCs express ______ MHC and costimulatory molecules, thus ______ polarize Th1 and _____ sensitize CD8 cytotoxic cells

Lower; poorly; inefficiently 

Vectors for yellow fever virus

Aedes aegypti and aedes albopictus (mosquitoes)

Vectors for Zika virus

Aeres aegypti and aeres albopictus (same as YFV)

Zika virus Sx

Fever, skin rash, arthralgia, conjunctivitis, muscle pain, and headache

Infants with Zika virus outcomes 

Microencephaly, abnormal eye development, hearing loss, abnormal limbs and joints, calcium deposits in brain (indicative of damage), and absent or poorly formed brain structures

Zika virus transmission

Mosquito vectors (primary)

alternate routes: vertical transmission, sexual contact, and blood transfusion

Vaccine for Zika virus

Does not exist