W5 Flashcards
(25 cards)
What are virulence factors influenced by?
Both the microbe and the host’s role in disease
Why should research focus on microbe-host interactions?
To better understand how disease severity is influenced by both the pathogen and host response
Was SARS-CoV-2 a “successful” pathogen, or was severity due to the host response?
Severity may have been driven by host immune dysregulation rather than the virus itself
Which TLRs detect SARS-CoV-2 RNA?
TLR3 detects dsRNA, and TLR7 detects ssRNA.
What adaptor proteins do TLR3 and TLR7 use?
TLR3: Uses TRIF, leading to IRF3 activation and Type I IFN production.
TLR7: Uses MyD88, leading to IRF7 activation and Type I IFN production.
What is the role of interferons (IFNs) in viral infections?
They induce an antiviral state and help contain viral replication
Why is interferon (IFN) dysregulation significant in SARS-CoV-2 infection?
It disrupts early viral control and leads to severe disease outcomes
What happens when IFN production is too strong early in infection?
Severe disease due to excessive immune activation
What happens when IFN production is too weak early in infection?
Poor viral control, leading to excessive inflammation and severe symptoms
What clinical observations suggest IFN dysregulation in SARS-CoV-2 patients?
Poor oxygen saturation (affecting macrophage respiratory burst).
Low antibody production.
Failure to transition from innate to adaptive immunity.
What did the IFNAR knockout mouse experiment suggest?
The severe disease may be host-driven rather than purely viral-induced
What happens if the innate immune response is properly regulated?
Early Type I IFN induction clears the virus.
Mild or asymptomatic infection.
What happens if innate immunity is poorly regulated?
Cytokine storm (excess cytokine production).
Severe symptoms and acute respiratory distress syndrome (ARDS).
What role does the inflammasome play in severe COVID-19?
It increases IL-1β production, leading to excessive inflammation
What host conditions predispose individuals to severe COVID-19?
Increased basal IL-1β production (obesity, heart disease, hypertension).
Decreased Type I IFN production (age, genetic mutations, autoantibodies).
How does SARS-CoV-2 push the immune system into a hyperinflammatory state?
By promoting IL-1β secretion while inhibiting Type I IFNs
What are the three major categories of SARS-CoV-2 proteins?
Non-Structural Proteins (NSPs): Critical for transcription and replication.
Structural Proteins: Spike (S), Envelope (E), Membrane (M), and Nucleocapsid (N).
Accessory Proteins: Not essential for viral replication but help evade immunity.
Which structural protein is responsible for host cell entry?
Spike (S) protein
What viral proteins suppress interferon production?
NSP1, NSP3, NSP12-16 (Non-Structural Proteins).
ORF3 and ORF6 (Accessory Proteins).
Membrane (M) and Nucleocapsid (N) proteins.
How does NSP16 evade the immune response?
It mimics cellular mRNA by methylating viral RNA to escape detection
How does the ORF6 protein interfere with interferon signaling?
It blocks STAT1 translocation to the nucleus, preventing IFN signaling.
What happens when STAT1 cannot enter the nucleus?
The host cell cannot produce antiviral proteins (AVPs), allowing viral replication.
Why is an effective innate immune response important for adaptive immunity?
It helps activate T cells and antibody production for long-term protection.
What prevents proper adaptive immunity in SARS-CoV-2 patients?
Interferon dysregulation
Delayed or excessive cytokine response
Inflammasome overactivation
