22: Viruses

Why are viruses considered non-living

Can’t produce their own energy

Types of viral genome

DNA or RNA

What does it mean if a virus is “enveloped”

Surrounded by a lipid bilayer

Key component for viruses to get into cells

Matching receptors on host cell and viral capsule

Steps of a viral infection

• Attachment

• Entry

• Synthesis

• Assembly

• Release

Mechanisms for viral entry

• Membrane fusion

• Receptor mediated endocytosis

Types of barriers of the immune system

• Mechanical (skin)

• Chemical (pH, enzymes, etc.)

• Microbiological

Where does most viral entry happen

Mucosa

Which types of immune cells are involved in a viral response

Most innate cells

Which types of immune cells are not involved in a viral response

Basophils and eosinophils

Main roles of immune response to viruses

• Alert body to presence of pathogen

• Attempt to mitigate entry

Which antigen presenting molecule is key in viral infections

MHC-I (intracellular pathogen!)

Key antigens (PAMPs) of a virus

• DNA and dsRNA

• Structural proteins

• Non-structural proteins (spikes)

Locations of receptors that ID viruses

• Plasma Membrane

• Endosome

• Cytosol

Types of plasma membrane receptors that ID viruses

TLR4

What does TLR4 recognize

LPS and other structural proteins

Types of endosome receptors that ID viral NAs

• TLR3

• TLR7/8

• TLR9

What does TLR3 recognize

dsRNA

What does TLR7/8 recognize

ssRNA

What does TLR9 recognize

DNA

Types of cytosol receptors/pathways that ID viruses

• RIG-I

• STING pathway

• INLRP3

What does RIG-I recognize

dsRNA in cytosol

What does the STING pathway recognize

DNA in cytosol

What does NLRP3 recognize

Inflammasomes (? not entirely clear)

Purpose of inflammation in viral infections

Alerts cells and recruits immune cells

Antiviral immune mechanisms

• Promotes cell death

• Release of Type 1 IFNs

What IFNs are Type 1 interferons

alpha, beta, and gamma

Action of Type 1 IFNs

Creates an anti-viral state by upregulating IFN Stimulated Genes, which produce enzymes to produce anti-viral proteins

How are Type 1 IFNs secreted/received

Paracrine or autocrine

First immune cell to be recruited to site of viral infection

Neutrophils

Defense mechanisms of neutrophils in viral infections

• Pro-inflammatory signaling

• Phagocytosis and lysis

• Degranulation

• Histone and DNA Nets

What other immune cells do neutrophils recruit

Macrophages

What immune cell is the major player in viral infections

NK cells

How are NK cells activated

• Loss of normal MHC I

• Fc receptors

• Cytokines

How do NK cells kill

Perforin-granzyme pathway

What T cells are associated with viral infections

• T_H cell

• CD8

T_H cell associated with viral infections

T_H1

How does T_H1 help fight viruses

Induces an anti-viral state

How do CD8 cells help fight viruses

Kill cells

Signals for CD8 cells to destroy a cell

• FAS/FASL interaction

• Threshold amount of pro-inflammatory cytokines

Which antibodies are prevalent in viral infections

• IgM

• IgG

• IgA

Which antibody is first on the scene

IgM

Which antibody is most abundant and long lasting

IgG

Which antibody can’t activate complement

IgA

Functions of antibodies

• Neutralization

• Opsonization

• Complement activation

How do antibodies activate the classical complement pathway

By forming an Ag-Ab complex

How do complement proteins fight viruses

Formation of the membrane attack complex in host or viral cells

Which branch of the immune system does the actual clearing of the virus

Adaptive

How do viruses evade the immune system

• Mutation of non-structural proteins

• Down regulation of host MHC molecules

• Sabotages every immune signaling pathway

• Prevents receptor ligand interaction

Antigenic drift

Small mutations that typically increase pathogenicity and virulence

Antigenic shift

Introduction of new genomic material