Topic 32 - Dengue/Lassa + Arenaviruses + Hemorrhagic Fever

Why are dengue infections rapidly increasing?

Urbanization/Global + spread of mosquito vector

What mosquito transmits dengue?

Aedes aegypti

Where does the Aedes aegypti mosquito thrive?

Tropical, urban environments

Why did dengue spread globally?

Movement during WWII + expansion of mosquito habitat

How many dengue infections occur per year?

~400 million

What is Antibody-Dependent Enhancement (ADE)?

Antibodies enhance viral infection instead of neutralizing it

What is the first step in the ADE mechanism?

Antibodies bind virus (but weakly)

What happens after the virus-antibody complex binds?

Virus-Ab complex binds Fc receptor on macrophages

What occurs after the virus enters immune cells?

Increased viral replication

What type of antibodies cause ADE?

Sub-neutralizing antibodies

Why are macrophages heavily infected in dengue?

Fc receptor-mediated entry

What happens to viral production during ADE?

↑ 5-7x increase

Who are the 2 main risk groups for dengue hemorrhagic fever?

Previously infected with different serotype and infants (maternal antibodies)

Why do these groups get severe disease?

They have sub-neutralizing antibodies

What cells does dengue infect?

Monocytes/macrophages & dendritic cells

What causes bleeding in dengue?

Cytokine-induced vascular leakage (NOT direct vessel destruction)

What is thrombocytopenia?

Low platelet count → worsens bleeding

What is Dengvaxia?

Tetravalent dengue vaccine

Why is the dengue vaccine problematic?

Can increase risk of severe disease (ADE)

Who should receive the dengue vaccine?

ONLY previously infected individuals

What type of genome do arenaviruses have?

(-) ssRNA, 2 segments, ambisense

What is unique about arenavirus virions?

Contain nonfunctional ribosomes ("sandy" appearance)

What is the natural host for arenaviruses?

Rodents

How do humans get infected with arenaviruses?

Inhalation/contact with rodent urine/feces

What happens first in Lassa fever phase 1?

URT infection

What are the symptoms of Lassa fever phase 1?

Fever, sore throat, headache

What happens in phase 2 of Lassa fever?

Virus spreads through body

What are key symptoms of phase 2 in Lassa fever?

Edema, rash, capillary leakage, shock

What is the final stage of Lassa fever?

Coma → death

What causes death in Lassa fever?

Capillary leakage → hypovolemic shock

What drug reduces mortality in arenavirus infections?

Ribavirin

How to control arenaviruses?

Rodent control

How many genome segments do arenaviruses have?

2

What coding strategy do arenaviruses use?

Ambisense

What virus are arenaviruses related to?

Hantavirus

How might arenaviruses have evolved?

Recombination of Hantavirus segments

What is needed for recombination in arenaviruses?

Homologous sequences

What is the most important dengue concept?

ADE

What causes severe dengue?

Cytokine storm + vascular leakage

Who gets severe dengue?

Previously infected + infants

What is the main transmission route of arenaviruses?

Rodent urine/feces

What causes hemorrhage in Lassa fever?

Capillary leakage

What makes the arenavirus genome unique?

Ambisense + 2 segments