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?

<p>Maturation (D)</p> Signup and view all the answers

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

<p>The cell becomes infected but does not support viral replication. (A)</p> Signup and view all the answers

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

<p>To initiate the infectious cycle (D)</p> 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?

<p>Permissiveness (C)</p> Signup and view all the answers

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

<p>By interfering with the presentation of viral peptides within MHC I complexes (B)</p> Signup and view all the answers

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

<p>The cell does not become infected. (D)</p> Signup and view all the answers

What is a characteristic of latent infections?

<p>The viral genome persists intact within the infected cell (D)</p> Signup and view all the answers

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

<p>Stimulating the production of antibodies against the virus (B)</p> Signup and view all the answers

What is the primary site of infection for herpesviruses?

<p>Epithelial mucosal cells (B)</p> Signup and view all the answers

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

<p>Through saliva and sexual contact (A)</p> Signup and view all the answers

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

<p>The virus can establish latency in sensory ganglia (C)</p> Signup and view all the answers

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

<p>To maintain the latent state (C)</p> Signup and view all the answers

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

<p>Delayed or prevented elimination of the virus by cytotoxic T cells (A)</p> Signup and view all the answers

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

<p>To address the amino acid substitutions in the hemagglutinin of influenza viruses (A)</p> Signup and view all the answers

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

<p>Epithelial cells (C)</p> 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?

<p>It is an acute infection (C)</p> Signup and view all the answers

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

<p>There is no single mechanism (D)</p> Signup and view all the answers

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

<p>Transporting nucleocapsids to the neuronal cell body via retrograde transport (A)</p> Signup and view all the answers

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

<p>A persistent infection (A)</p> Signup and view all the answers

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

<p>Killing of epithelial cells (C)</p> 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?

<p>Viral pathogenesis (C)</p> Signup and view all the answers

What is the function of LAT during latency?

<p>Suppressing viral lytic gene expression (A)</p> Signup and view all the answers

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

<p>It perpetuates a persistent infection (D)</p> Signup and view all the answers

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

<p>Production of new viruses and re-infection of epithelial cells (D)</p> Signup and view all the answers

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

<p>Neuronal cell nucleus (D)</p> Signup and view all the answers

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

<p>It affects the virus-receptor binding site (A)</p> Signup and view all the answers

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

<p>Bacterial infection, hormonal changes, environmental stress (D)</p> Signup and view all the answers

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

<p>It makes a persistent infection more likely (C)</p> Signup and view all the answers

What is the outcome of viral reactivation in sensory neurons?

<p>Infection of epithelial cells and production of new viruses (B)</p> Signup and view all the answers

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

<p>Immunopathology (C)</p> Signup and view all the answers

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

<p>No protection against other serotypes (C)</p> 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?

<p>Clinical manifestations (C)</p> Signup and view all the answers

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

<p>Both b and c (C)</p> Signup and view all the answers

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

<p>Agonizing limb pain (C)</p> Signup and view all the answers

How many serotypes of dengue virus are there?

<p>4 (A)</p> Signup and view all the answers

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

<p>Tissue damage (B)</p> Signup and view all the answers

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

<p>Damage to the host (B)</p> Signup and view all the answers

What type of RNA does RIG-1 detect?

<p>5' triphosphate RNA (A)</p> Signup and view all the answers

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

<p>To inhibit cap-dependent translation (D)</p> Signup and view all the answers

What type of nucleic acid does cGAS bind to?

<p>Viral dsDNA (B)</p> Signup and view all the answers

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

<p>It makes the domain inactive (B)</p> Signup and view all the answers

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

<p>To polyubiquitylate and activate CARD domains (A)</p> Signup and view all the answers

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

<p>To detect viral RNA and activate the immune response (B)</p> Signup and view all the answers

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

<p>To block the majority of infections (B)</p> Signup and view all the answers

What is the characteristic of intrinsic defense responses?

<p>They can be achieved by a single cell in isolation (C)</p> Signup and view all the answers

What happens if viruses bypass the physical and chemical barriers?

<p>A series of immune responses are engaged (C)</p> Signup and view all the answers

What is the coordinated host response to infection?

<p>The integration of intrinsic defense with innate and adaptive immune systems (C)</p> Signup and view all the answers

What is the characteristic of the innate immune response?

<p>It is induced by infection (A)</p> Signup and view all the answers

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

<p>The coordinated host response to infection is engaged (C)</p> Signup and view all the answers

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

<p>To recognize and respond to foreign microorganisms (C)</p> Signup and view all the answers

Where can pattern recognition receptors be located in host cells?

<p>On the host cell surface, endosomal membranes, cytoplasm, or secreted (C)</p> Signup and view all the answers

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

<p>Cell signaling and immune response (B)</p> Signup and view all the answers

What is an example of a MAMP?

<p>dsRNA (C)</p> Signup and view all the answers

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

<p>To recognize and respond to foreign microorganisms (B)</p> Signup and view all the answers

What is the result of MAMP-receptor engagement?

<p>Cell signaling and immune response (D)</p> Signup and view all the answers

What is a characteristic of MAMPs?

<p>They are shared among groups of microorganisms (B)</p> Signup and view all the answers

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

<p>To recognize and respond to foreign microorganisms (B)</p> Signup and view all the answers

What is the function of Type I IFNs?

<p>To establish an antiviral response (B)</p> Signup and view all the answers

What is the role of cGAS in the immune response?

<p>To detect and respond to viral nucleic acids (C)</p> Signup and view all the answers

What is the effect of ubiquitylation on STING?

<p>It activates STING (C)</p> Signup and view all the answers

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

<p>Production of antiviral proteins (B)</p> Signup and view all the answers

What is the function of STING in the immune response?

<p>To promote the expression of Type I IFNs and pro-inflammatory cytokines (A)</p> Signup and view all the answers

What is the function of PKR in the immune response?

<p>To phosphorylate eIF2α and inhibit protein synthesis (C)</p> Signup and view all the answers

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

<p>Inactivated STING allows viral replication (B)</p> Signup and view all the answers

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

<p>To activate RNase L (D)</p> Signup and view all the answers

What is the function of cytokines in the immune response?

<p>To mediate cell-cell communication and regulate immune responses (A)</p> Signup and view all the answers

What is the function of IFNAR receptors?

<p>To bind Type I IFNs and establish an antiviral response (A)</p> Signup and view all the answers

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

<p>Inhibition of viral replication (C)</p> Signup and view all the answers

How do viruses evade cGAS responses?

<p>All of the above (D)</p> Signup and view all the answers

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

<p>Production of antiviral proteins (A)</p> Signup and view all the answers

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

<p>Viral components bound by PRRs (A)</p> Signup and view all the answers

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

<p>To induce the synthesis of antiviral proteins (C)</p> Signup and view all the answers

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

<p>Synthesis of antiviral proteins (D)</p> Signup and view all the answers

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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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Lecture 5: Virus-Host Interaction Patterns of Infection
Host Immune Response Module 4B PDF

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