Virus-Host Interaction: Infectious Cycle and Pathogenesis

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Questions and Answers

What is the primary difference between susceptibility and permissiveness in the context of viral infection?

Susceptibility is a property of the virus, while permissiveness is a property of the host cell.

Susceptibility refers to the ability of a cell to become infected, while permissiveness refers to the ability of a cell to support viral replication. (correct)

Permissiveness is a measure of the strength of the host immune response, while susceptibility is a measure of the virus's ability to infect.

Susceptibility refers to the ability of a cell to support virus replication, while permissiveness refers to the presence of a virus receptor.

What is the first step in the viral infectious cycle?

Production of viral mRNA and viral protein synthesis

Assembly and release of viral particles

Genome replication

Attachment and entry (correct)

What is the primary requirement for productive infection to occur?

A susceptible and permissive host cell (correct)

A permissive host cell

A host cell with a strong immune response

A susceptible host cell

What is the final step in the viral infectious cycle?

Maturation Signup and view all the answers

What is the outcome of viral infection if a cell is susceptible but not permissive?

The cell becomes infected but does not support viral replication. Signup and view all the answers

What is the purpose of the entry and primary replication step in viral pathogenesis?

To initiate the infectious cycle Signup and view all the answers

What is the term for the ability of a cell to support virus replication when viral nucleic acid is introduced into the cell?

Permissiveness Signup and view all the answers

What is the primary mechanism by which viral proteins block the adaptive immune response?

By interfering with the presentation of viral peptides within MHC I complexes Signup and view all the answers

What is the outcome of viral infection if a cell is not susceptible but is permissive?

The cell does not become infected. Signup and view all the answers

What is a characteristic of latent infections?

The viral genome persists intact within the infected cell Signup and view all the answers

Which of the following is NOT a mechanism by which viral proteins block the adaptive immune response?

Stimulating the production of antibodies against the virus Signup and view all the answers

What is the primary site of infection for herpesviruses?

Epithelial mucosal cells Signup and view all the answers

How are HHV-1 and HHV-2 primarily transmitted?

Through saliva and sexual contact Signup and view all the answers

What is the characteristic of herpesviruses that ensures transmission to new hosts?

The virus can establish latency in sensory ganglia Signup and view all the answers

What is the function of viral gene products in latent infections?

To maintain the latent state Signup and view all the answers

What is the consequence of viral proteins blocking the adaptive immune response?

Delayed or prevented elimination of the virus by cytotoxic T cells Signup and view all the answers

What is the primary reason for the development of a new influenza vaccine every year?

To address the amino acid substitutions in the hemagglutinin of influenza viruses Signup and view all the answers

What is the primary site of herpes simplex virus (HSV-1) infection?

Epithelial cells Signup and view all the answers

What is the characteristic of a viral infection that is cleared by the immune system in a short period of time?

It is an acute infection Signup and view all the answers

What is the primary mechanism responsible for establishing a persistent infection?

There is no single mechanism Signup and view all the answers

What is the role of microtubule-based systems in the establishment of latency?

Transporting nucleocapsids to the neuronal cell body via retrograde transport Signup and view all the answers

What is the result of a viral infection that is not cleared by the immune system?

A persistent infection Signup and view all the answers

What is the outcome of immune responses to HSV-1 infection in epithelial cells?

Killing of epithelial cells Signup and view all the answers

What is the term for the adverse physiological consequences that occur as a result of viral infection of the host organism?

Viral pathogenesis Signup and view all the answers

What is the function of LAT during latency?

Suppressing viral lytic gene expression Signup and view all the answers

What is the role of modulation of the adaptive immune response in establishing a persistent infection?

It perpetuates a persistent infection Signup and view all the answers

What is the result of viral lytic gene expression during reactivation?

Production of new viruses and re-infection of epithelial cells Signup and view all the answers

What is the site of viral DNA release during the establishment of latency?

Neuronal cell nucleus Signup and view all the answers

What is the significance of the distribution of amino acid residue changes in the hemagglutinin of influenza viruses?

It affects the virus-receptor binding site Signup and view all the answers

What is the trigger for the reactivation of latent HSV-1?

Bacterial infection, hormonal changes, environmental stress Signup and view all the answers

What is the consequence of a reduction in host defenses in the establishment of a persistent infection?

It makes a persistent infection more likely Signup and view all the answers

What is the outcome of viral reactivation in sensory neurons?

Infection of epithelial cells and production of new viruses Signup and view all the answers

What is the term used to describe the damage caused by the host's immune response to infection?

Immunopathology Signup and view all the answers

What is the consequence of having antibodies to one serotype of dengue virus?

No protection against other serotypes Signup and view all the answers

What is the term used to describe the clinical signs of viral disease, such as fever, aches, and tissue damage?

Clinical manifestations Signup and view all the answers

What is the result of the destruction of lymphoid tissue in AIDS?

Both b and c Signup and view all the answers

What is the typical symptom of dengue fever described as 'break bone' pain?

Agonizing limb pain Signup and view all the answers

How many serotypes of dengue virus are there?

4 Signup and view all the answers

What is the result of the host's immune response to infection in the context of immunopathology?

Tissue damage Signup and view all the answers

What is the consequence of immunopathology in the context of viral disease?

Damage to the host Signup and view all the answers

What type of RNA does RIG-1 detect?

5' triphosphate RNA Signup and view all the answers

What is the function of protein kinase R (PKR)?

To inhibit cap-dependent translation Signup and view all the answers

What type of nucleic acid does cGAS bind to?

Viral dsDNA Signup and view all the answers

What is the effect of phosphorylation on CARD domains in uninfected cells?

It makes the domain inactive Signup and view all the answers

What is the function of Ubiquitin Ligases in the activation of CARD domains?

To polyubiquitylate and activate CARD domains Signup and view all the answers

What is the function of RIG-1 and MDA5 in the immune response?

To detect viral RNA and activate the immune response Signup and view all the answers

What is the primary function of the physical barriers in the host immune response?

To block the majority of infections Signup and view all the answers

What is the characteristic of intrinsic defense responses?

They can be achieved by a single cell in isolation Signup and view all the answers

What happens if viruses bypass the physical and chemical barriers?

A series of immune responses are engaged Signup and view all the answers

What is the coordinated host response to infection?

The integration of intrinsic defense with innate and adaptive immune systems Signup and view all the answers

What is the characteristic of the innate immune response?

It is induced by infection Signup and view all the answers

What is the result of the integration of intrinsic defense with innate and adaptive immune systems?

The coordinated host response to infection is engaged Signup and view all the answers

What is the role of MAMPs in the host immune response?

To recognize and respond to foreign microorganisms Signup and view all the answers

Where can pattern recognition receptors be located in host cells?

On the host cell surface, endosomal membranes, cytoplasm, or secreted Signup and view all the answers

What is the outcome of receptor-mediated recognition of MAMPs?

Cell signaling and immune response Signup and view all the answers

What is an example of a MAMP?

dsRNA Signup and view all the answers

What is the function of PRRs in the host immune response?

To recognize and respond to foreign microorganisms Signup and view all the answers

What is the result of MAMP-receptor engagement?

Cell signaling and immune response Signup and view all the answers

What is a characteristic of MAMPs?

They are shared among groups of microorganisms Signup and view all the answers

What is the purpose of the recognition of MAMPs by PRRs?

To recognize and respond to foreign microorganisms Signup and view all the answers

What is the function of Type I IFNs?

To establish an antiviral response Signup and view all the answers

What is the role of cGAS in the immune response?

To detect and respond to viral nucleic acids Signup and view all the answers

What is the effect of ubiquitylation on STING?

It activates STING Signup and view all the answers

What happens after Type I IFNs bind to IFNAR receptors on adjacent cells?

Production of antiviral proteins Signup and view all the answers

What is the function of STING in the immune response?

To promote the expression of Type I IFNs and pro-inflammatory cytokines Signup and view all the answers

What is the function of PKR in the immune response?

To phosphorylate eIF2α and inhibit protein synthesis Signup and view all the answers

What is the outcome of viral manipulation of STING post-translational modifications?

Inactivated STING allows viral replication Signup and view all the answers

What is the role of 2',5'-oligo A synthetase in the immune response?

To activate RNase L Signup and view all the answers

What is the function of cytokines in the immune response?

To mediate cell-cell communication and regulate immune responses Signup and view all the answers

What is the function of IFNAR receptors?

To bind Type I IFNs and establish an antiviral response Signup and view all the answers

What is the effect of Type I IFNs on viral replication?

Inhibition of viral replication Signup and view all the answers

How do viruses evade cGAS responses?

All of the above Signup and view all the answers

What is the outcome of Type I IFN synthesis and secretion?

Production of antiviral proteins Signup and view all the answers

What is the trigger for the production of Type I IFNs?

Viral components bound by PRRs Signup and view all the answers

What is the role of IFNAR receptors in the immune response?

To induce the synthesis of antiviral proteins Signup and view all the answers

What is the outcome of the binding of Type I IFNs to IFNAR receptors?

Synthesis of antiviral proteins Signup and view all the answers

Study Notes

Virus-Host Interaction: Patterns of Infection

The infectious cycle includes attachment and entry, production of viral mRNA and viral protein synthesis, genome replication, assembly and release of viral particles, and maturation.

Viral Pathogenesis

Productive infection requires a susceptible and permissive host cell
The infectious process involves entry and primary replication, viral spread, cellular injury, host immune response, viral clearance or establishment of persistent infection, and viral shedding

Susceptibility and Permissiveness

Susceptibility refers to the capacity of a cell to become infected by a virus, determined by the presence of a virus receptor expressed by the host cell
Permissiveness refers to the ability of a cell to support virus replication when viral nucleic acid is introduced into the cell

Patterns of Infection

Acute infection: virus particles produce rapidly, and infection is resolved quickly by the immune system (short-term infection)
Persistent infection: virus particles produce slowly, and infection is not cleared by the immune system (long-term infection)
Persistent infection can be divided into latent, asymptomatic, and pathogenic types

Persistent Infections

No single mechanism is responsible for establishing a persistent infection
Viral proteins may block the adaptive immune response, preventing elimination of the virus by cytotoxic T cells
Latent infections are characterized by:
Viral gene products that promote virus reproduction are not synthesized (or synthesized in small quantities)
Cells that contain the viral genome are poorly recognized by the immune system
The viral genome persists intact within the infected cell to ensure productive infection may be initiated at a later time

Herpesviruses

Enveloped viruses with a dsDNA genome
Transmission: HHV-1 through saliva, HHV-2 through sexual contact and maternal-neonatal transmission
Infection: primary site of infection is epithelial mucosal cells, latency established in sensory ganglia
Associated diseases: skin vesicles or mucosal ulcers

Herpes Simplex Virus (HSV-1)

Infection of epithelial cells and sensory neurons
Latency established in sensory ganglia
Factors such as bacterial infection, hormonal changes, and environmental stress can reactivate the virus
Reactivation involves travel down the axons of the sensory neurons and re-infection of epithelial tissues

Immunopathology

Clinical signs of viral disease (fever, aches, tissue damage, nausea) largely stem from the host's immune response to infection
This damage is referred to as 'immunopathology' (may be the price to pay by the host to eliminate infection!)

PRRs that are good to know

RIG-1 and MDA5 are cytoplasmic RNA helicases that function as RNA sensors.
RIG-1 detects 5' triphosphate RNA (without 5' cap) in the cytoplasm.
MDA5 detects long dsRNA (and RNA without 5' cap).
Protein kinase R (PKR) is a sensor for viral dsRNA that inhibits cap-dependent translation by eIF2α.
cGAS (cyclic GMP-AMP synthase) binds to viral dsDNA in the cytoplasm and undergoes a conformational change to expose a part that allows the binding of phosphotases.

Activating CARD domains

RIG-1 and MDA5 contain tandem N-terminal CARD domains.
In uninfected cells, CARD domains are phosphorylated (inactive conformation).
Dephosphorylated CARD domains are further activated through polyubiquitylation by ubiquitin ligases (TRIM25 and/or Riplet).

Host Immune Response

The coordinated host response to infection involves intrinsic, innate, and adaptive immune systems.
Cell-autonomous responses can be achieved by a single cell in isolation and are induced by infection.
These responses are tailored to the specific pathogen.

Intrinsic Defense

Physical and chemical barriers block the majority of infections.
Viruses that bypass these barriers trigger a series of immune responses.

MAMPs and PRRs

MAMPs (macromolecules associated with microorganisms) are recognized as foreign to the host.
Examples of MAMPs include dsRNA, peptidoglycan, LPS, flagellin, and viral proteins.
PRRs (pattern recognition receptors) recognize MAMPs and may be located on the host cell surface, endosomal membranes, cytoplasmic, or secreted.

Cellular Response

Receptor-mediated recognition of MAMPs by PRRs induces cell signaling.
Activated STING translocates to perinuclear structures where it promotes expression of Type I IFNs and pro-inflammatory cytokines.

Viral Evasion

Viruses evade cGAS responses through mechanisms such as viral manipulation of STING post-translational modifications, cleavage of STING, and prevention/limitation of cGAS sensing of nucleic acid ligand.

Cytokines

Cytokines are small signaling proteins that are secreted by specific immune cells.
Interferons (IFNs) are a group of cytokines that are generated in response to several pathogens.

Type I IFNs

Type I IFNs (α/β) are induced following PRR signaling and bind to IFNAR receptors on target cells.
Type I IFNs help to establish an antiviral response.

Type I IFN Synthesis and Signaling

Type I IFN synthesis, secretion, receptor binding, and signal transduction are triggered by viruses or viral components bound by PRRs.
Type I IFNs promote upregulation of antiviral proteins such as PKR and 2',5'-oligo A synthetase.

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Description

This quiz covers the principles of virology, focusing on the infectious cycle, including attachment, entry, genome replication, and release of viral particles, as well as viral pathogenesis, including entry, spread, and cellular injury.