Viral Infection Patterns
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Questions and Answers

What is a characteristic of survivors of viral infections?

  • They are more susceptible to subsequent infections
  • They have a weaker immune system
  • They are usually immune to subsequent infections (correct)
  • They are asymptomatic carriers of the virus

    • What is the primary mechanism by which viral proteins block the Adaptive Immune Response?

  • By enhancing the expression of MHC I genes
  • By producing antibodies that bind to MHC I complexes
  • By blocking the production of proteasome-derived viral peptides (correct)
  • By stimulating the production of cytokines that suppress cytotoxic T cells

    • What is a persistent infection?

  • A latent viral infection that is cleared by the immune system
  • A long-term viral infection that is not cleared by the immune system (correct)
  • An asymptomatic viral infection that is transmitted to other hosts
  • A short-term viral infection that is cleared by the immune system

    • What happens to viral genomes in a persistent infection?

    <p>They may remain in the host</p> Signup and view all the answers

    What is a characteristic of latent infections?

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

    What is the primary site of infection for Herpesviruses?

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

    What is a characteristic of acute infections?

    <p>They may be resolved within a few days</p> Signup and view all the answers

    How are Herpesviruses transmitted?

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

    What is antigenic variation?

    <p>A mechanism of immune evasion</p> Signup and view all the answers

    What is antigenic drift?

    <p>An accumulated mutation in the viral genome that results in a substantial change in genetic makeup</p> Signup and view all the answers

    What is the role of latent infections in the viral life cycle?

    <p>To ensure productive infection at a later time</p> Signup and view all the answers

    What type of viral genome do Herpesviruses possess?

    <p>dsDNA</p> Signup and view all the answers

    What is a characteristic of well-adapted pathogens?

    <p>They can cause asymptomatic infections</p> Signup and view all the answers

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

    <p>To promote the persistence of the viral genome</p> Signup and view all the answers

    Why may acute infections be inapparent?

    <p>Because the virus replication is limited, but still facilitates transmission</p> Signup and view all the answers

    What is the outcome of viral modulation of the Adaptive Immune Response?

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

    What is the primary characteristic of an acute viral infection?

    <p>Virus particles are produced rapidly, and the infection is resolved quickly</p> Signup and view all the answers

    What occurs during the incubation period?

    <p>The immune system produces cytokines and viral genomes are replicated</p> Signup and view all the answers

    What is the term for the adverse physiological consequences of viral infection?

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

    What is the characteristic of persistent-latent infection?

    <p>Periodic episodes of acute infections followed by quiescent phase</p> Signup and view all the answers

    What is the duration of an acute viral infection?

    <p>7-10 days</p> Signup and view all the answers

    What is the characteristic of persistent-asymptomatic infection?

    <p>Virus production continues for the life of the host or in tissues where immune cells do not often patrol</p> Signup and view all the answers

    What is the characteristic of persistent-pathogenic infection?

    <p>A period of years separates primary infection and fatal appearance of symptoms</p> Signup and view all the answers

    What is the purpose of the incubation period?

    <p>To allow the virus to replicate and produce cytokines</p> Signup and view all the answers

    What type of cells does HSV-1 primarily infect?

    <p>Epithelial cells</p> Signup and view all the answers

    What is the direction of transport of nucleocapsids in sensory neurons?

    <p>Retrograde</p> Signup and view all the answers

    What is the role of LAT in HSV-1 infection?

    <p>Suppresses viral gene expression</p> Signup and view all the answers

    What triggers the reactivation of HSV-1?

    <p>Hormonal changes and environmental stress</p> Signup and view all the answers

    Where does the HSV-1 genome persist in a latent state?

    <p>Sensory neurons</p> Signup and view all the answers

    What is the outcome of the immune response to HSV-1 infection?

    <p>Killing of epithelial cells, producing a new sore</p> Signup and view all the answers

    How does the virus travel from sensory neurons to epithelial tissues?

    <p>Down the axons of the sensory neurons</p> Signup and view all the answers

    What event marks the reactivation of HSV-1?

    <p>Viral lytic gene expression is initiated</p> Signup and view all the answers

    What is the primary reason why mice infected with Lymphocytic Choriomeningitis Virus congenitally or immediately after birth do not develop encephalitis and edema?

    <p>The virus is non-cytopathic</p> Signup and view all the answers

    During latent infection, what is the primary function of LATs?

    <p>To block transcription of lytic genes</p> Signup and view all the answers

    What is the characteristic of HIV infection during the asymptomatic phase?

    <p>Low viremia and slowly declining CD4+ T cell numbers</p> Signup and view all the answers

    What is the outcome of persistent infection with Lymphocytic Choriomeningitis Virus on the cognitive abilities of mice?

    <p>The infected mice have impaired cognitive abilities</p> Signup and view all the answers

    What is the duration of the acute phase of HIV infection?

    <p>Several weeks</p> Signup and view all the answers

    What is the primary mechanism by which the immune response controls HIV infection during the acute phase?

    <p>CTLs and antibodies against HIV</p> Signup and view all the answers

    What is the characteristic of HIV infection during the acute phase?

    <p>High levels of virus in the blood and a rapid decline of CD4+ T cells</p> Signup and view all the answers

    What is the primary difference between the asymptomatic phase of HIV infection and the acute phase?

    <p>The levels of virus in the blood are lower during the asymptomatic phase</p> Signup and view all the answers

    What type of receptors are expressed in certain cell types such as macrophages and dendritic cells?

    <p>Toll-like receptors (TLRs)</p> Signup and view all the answers

    What is the outcome of MAMP-PRR engagement?

    <p>Activation of transcription factors such as NFkB and IRFs</p> Signup and view all the answers

    What type of RNA can act as a MAMP?

    <p>Double-stranded RNA</p> Signup and view all the answers

    What is the function of adaptor proteins in PRR signaling?

    <p>To activate Nf-kb and Irf</p> Signup and view all the answers

    What is the outcome of activation of NFkB and IRFs?

    <p>Expression of IFNs and inflammatory cytokines</p> Signup and view all the answers

    Where are cell surface PRRs located?

    <p>On the cell surface</p> Signup and view all the answers

    What is the function of RIG-1-like receptors (RLRs)?

    <p>To recognize MAMPs in the cytosol</p> Signup and view all the answers

    What type of cytokines are expressed as a result of PRR signaling?

    <p>Inflammatory cytokines</p> Signup and view all the answers

    What occurs upon binding of viral RNA to PRRs?

    <p>CARDs are dephosphorylated</p> Signup and view all the answers

    What is the role of RIG-1 and MDA5 in their active conformations?

    <p>Recruitment and activation of IKK and TBK1</p> Signup and view all the answers

    What is the function of specific phosphatases in the viral response?

    <p>Dephosphorylation of CARDs</p> Signup and view all the answers

    What is the role of MAVs in the viral response?

    <p>Mitochondrial antiviral signaling protein</p> Signup and view all the answers

    What is the outcome of RIG-1 and MDA5 activation?

    <p>Activation of NF-KB and IRF3 and IRF7</p> Signup and view all the answers

    What is the mechanism by which viruses evade RIG-1 and MDA5 responses?

    <p>Specific mechanism is not mentioned in the text</p> Signup and view all the answers

    What is the function of IKK and TBK1 in the viral response?

    <p>Transcriptional activation of NF-KB</p> Signup and view all the answers

    What is the outcome of the interaction between RIG-1 and MAVs?

    <p>Recruitment and activation of IKK and TBK1</p> Signup and view all the answers

    What is the outcome of PKR activation through dsRNA binding?

    <p>Inhibition of cap-dependent translation initiation</p> Signup and view all the answers

    What is the effect of RIG-1, MDA5, and MAVS cleavage?

    <p>Deregulation of the immune response</p> Signup and view all the answers

    What is the consequence of viral RNA ligand sequestration?

    <p>Deregulation of the immune response</p> Signup and view all the answers

    What is the mechanism of translational arrest induced by PKR?

    <p>Phosphorylation of eIF2α</p> Signup and view all the answers

    What is the outcome of post-translational modifications on RIG-1, MDA5, and MAVS?

    <p>Deregulation of the immune response</p> Signup and view all the answers

    What is the effect of RIG-1, MDA5, and MAVS relocalization?

    <p>Deregulation of the immune response</p> Signup and view all the answers

    What is the consequence of PKR dimerization and autophosphorylation?

    <p>Inhibition of cap-dependent translation initiation</p> Signup and view all the answers

    What is the outcome of viral manipulation of RIG-1, MDA5, and MAVS?

    <p>Deregulation of the immune response</p> Signup and view all the answers

    What is the primary function of RIG-1 in the cytoplasm?

    <p>Detects 5' triphosphate RNA</p> Signup and view all the answers

    What is the main difference between RIG-1 and MDA5?

    <p>RIG-1 detects 5' triphosphate RNA, while MDA5 detects long dsRNA</p> Signup and view all the answers

    What is the function of protein kinase R (PKR) in the context of viral infections?

    <p>Inhibits cap-dependent translation by eIF2α</p> Signup and view all the answers

    What is the result of cGAS binding to viral dsDNA in the cytoplasm?

    <p>Conformational change that exposes a part of CARD domains for binding of phosphotases</p> Signup and view all the answers

    What is the state of CARD domains in uninfected cells?

    <p>Phosphorylated</p> Signup and view all the answers

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

    <p>Polyubiquitylation of CARD domains</p> Signup and view all the answers

    What is the outcome of the dephosphorylation of CARD domains?

    <p>Activation of CARD domains</p> Signup and view all the answers

    What is the common feature of RIG-1 and MDA5?

    <p>Both contain tandem N-terminal CARD domains</p> Signup and view all the answers

    What is the result of inactive GDP-bound eIF-2?

    <p>Translation arrest</p> Signup and view all the answers

    Which of the following is not a mechanism used by viruses to evade PKR responses?

    <p>Stimulating the immune response</p> Signup and view all the answers

    What is the function of cGAS in the detection of viral infections?

    <p>Binding to viral dsDNA in the cytoplasm</p> Signup and view all the answers

    What is the outcome of eIF2α phosphorylation by PKR?

    <p>Inhibition of translation</p> Signup and view all the answers

    Which of the following is a mechanism used by viruses to counteract the antiviral response mediated by PKR?

    <p>Activating protein phosphatase to remove phosphorylated eIF2α</p> Signup and view all the answers

    What is the consequence of PKR-mediated eIF2α phosphorylation on viral protein synthesis?

    <p>Inhibition of viral protein synthesis</p> Signup and view all the answers

    What is the role of STING in the detection of viral infections?

    <p>Activating the antiviral response</p> Signup and view all the answers

    What is the outcome of the interaction between cGAS and viral dsDNA?

    <p>Generation of cyclic GMP-AMP</p> Signup and view all the answers

    What is the primary function of cilia in the upper respiratory tract?

    <p>To move mucus and its trapped contents to the throat</p> Signup and view all the answers

    What is the site of gas exchange in the lungs?

    <p>Alveoli</p> Signup and view all the answers

    What is the primary function of goblet cells in the respiratory tract?

    <p>To secrete mucus</p> Signup and view all the answers

    What is the approximate volume of air inhaled by a resting human every minute?

    <p>2 gallons</p> Signup and view all the answers

    What is the structure that increases the surface area of the epithelium in the small intestine?

    <p>Villi</p> Signup and view all the answers

    What type of cells are present in the alveoli of the lungs?

    <p>Alveolar macrophages</p> Signup and view all the answers

    What is the primary portal of entry for viruses into the human body?

    <p>Respiratory tract</p> Signup and view all the answers

    What is the characteristic of the mucosal surfaces of the respiratory tract?

    <p>They have a very large surface area</p> Signup and view all the answers

    What is the primary function of the placenta during pregnancy?

    <p>To act as an interface between the mother and developing fetus</p> Signup and view all the answers

    What determines the pattern of systemic illness produced during a viral infection?

    <p>Viral tropism</p> Signup and view all the answers

    What is the term for the presence of viruses in the blood?

    <p>Viremia</p> Signup and view all the answers

    What is the mechanism by which some viruses evade the immune response?

    <p>Directional release to the outer surface</p> Signup and view all the answers

    What is the primary requirement for a virus to cause a disease?

    <p>The virus must be able to attach to and enter cells of the host organism</p> Signup and view all the answers

    What is the term for the process by which viruses disseminate within the host?

    <p>Viral spread</p> Signup and view all the answers

    What is the primary route of viral dissemination within the host?

    <p>Bloodstream</p> Signup and view all the answers

    What is the term for the adverse physiological consequences of viral infection?

    <p>Pathogenesis</p> Signup and view all the answers

    What is the difference between viral virulence and cytopathogenicity?

    <p>Viral virulence refers to the ability of a virus to cause disease in a host, while cytopathogenicity refers to the ability of a virus to cause cell damage</p> Signup and view all the answers

    What is the term for the process by which viruses cross the placenta during pregnancy?

    <p>Transplacental infection</p> Signup and view all the answers

    What is the term for the site where viruses primarily replicate after entering the host?

    <p>Primary replication site</p> Signup and view all the answers

    What is the primary site of infection for viruses that enter the body through the respiratory tract?

    <p>Upper respiratory tract</p> Signup and view all the answers

    What is the function of goblet cells in the epithelium of the upper respiratory tract?

    <p>To produce mucus that traps inhaled particulate matter</p> Signup and view all the answers

    What is the term for the process by which a virus spreads from the initial site of infection to other parts of the body?

    <p>Viral spread</p> Signup and view all the answers

    What is the outcome of the host immune response to viral infection?

    <p>Viral clearance</p> Signup and view all the answers

    What is the final step in the viral pathogenesis process?

    <p>Viral shedding</p> Signup and view all the answers

    What is the primary route by which PV invades the CNS?

    <p>Directly through neural pathway from MNs in skeletal muscle</p> Signup and view all the answers

    What is the primary mechanism of HPV transmission?

    <p>Through breaks in the genital epithelium</p> Signup and view all the answers

    What is the primary site of viral replication for HPV in the skin?

    <p>Epidermis</p> Signup and view all the answers

    What is the term for the transmission of viruses from parents to their offspring?

    <p>Vertical transmission</p> Signup and view all the answers

    What is the consequence of vertical transmission of viruses?

    <p>Long-term persistence of the virus</p> Signup and view all the answers

    What is the primary mode of HBV transmission?

    <p>Through breaks in the genital epithelium</p> Signup and view all the answers

    What is the primary site of viral entry for HIV?

    <p>Genital epithelium</p> Signup and view all the answers

    What is the primary mechanism of viral replication in the skin?

    <p>Through replication in the epidermis</p> Signup and view all the answers

    What is the primary mechanism by which the host's immune response contributes to disease development?

    <p>Destruction of virus-infected cells in the target tissues</p> Signup and view all the answers

    What is the primary function of anatomical barriers in the host's defense against viral infections?

    <p>To provide a physical barrier against viral entry</p> Signup and view all the answers

    What is the primary difference between humoral immunity and cell-mediated immunity?

    <p>Humoral immunity is directed against extracellular infectious agents, while cell-mediated immunity is directed against intracellular infectious agents</p> Signup and view all the answers

    What is the primary function of phagocytes in the host's defense against viral infections?

    <p>To engulf and digest foreign particles and debris</p> Signup and view all the answers

    What is the term for the shedding of infectious virus into the environment?

    <p>Viral shedding</p> Signup and view all the answers

    What is the primary function of lysozymes in the host's defense against viral infections?

    <p>To break down bacterial cell walls</p> Signup and view all the answers

    What is the primary function of cytokines and inflammatory mediators in the host's defense against viral infections?

    <p>To coordinate the immune response and recruit immune cells</p> Signup and view all the answers

    What is the primary difference between innate and adaptive immune responses?

    <p>Innate immunity is nonspecific, while adaptive immunity is specific to a particular pathogen</p> Signup and view all the answers

    Study Notes

    Patterns of Viral Infection

    • Relative virus particle production plotted as a function of time after initial infection, showing symptoms and clearance
    • Acute infection: virus particles produced, symptoms appear, and infection is cleared (7-10 days)
    • Persistent infection: divided into latent, asymptomatic, and pathogenic types
    • Latent infection: periodic episodes of acute infections followed by quiescent phase
    • Asymptomatic infection: virus production continues for the life of the host or in tissues where immune cells do not often patrol
    • Pathogenic infection: fatal appearance of symptoms after a period of years, with continuous or undetectable virus production

    Incubation Period

    • Time before symptoms of disease appear following initial infection
    • During this period, viral genomes may be replicated and innate immune responses initiate production of cytokines

    Viral Pathogenesis

    • Adverse physiological consequences of viral infection in the host organism
    • Acute infection: rapid virus production and resolution by the immune system (short-term infection)
    • Persistent infection: not cleared by the immune system (long-term infection), with possible latent, asymptomatic, or pathogenic outcomes

    Acute Infection

    • Adaptive immune responses provide lasting protection to subsequent infections
    • Infection may be resolved within a few days, but viral progeny may still be shed and transmitted to other hosts
    • Inapparent (asymptomatic) acute infections may occur, with limited or no clinical symptoms detected

    Antigenic Variation

    • Accumulated mutation in viral genome, resulting in substantial change in genetic makeup
    • May facilitate repeated acute infections by evasion of the adaptive immune response

    Persistent Infections

    • Viral proteins may block adaptive immune response by blocking presentation of viral peptides within MHC I complexes
    • Latent infections characterized by:
      • Viral gene products not synthesized (or synthesized in small quantities)
      • Cells with the viral genome poorly recognized by the immune system
      • Viral genome persists intact within the infected cell for later productive infection

    Herpes Simplex Virus (HSV-1)

    • Enveloped virus with dsDNA genome
    • Transmission: saliva, sexual contact, maternal-neonatal
    • Infection: primary site - epithelial mucosal cells; latency established in sensory ganglia
    • Associated diseases: skin vesicles or mucosal ulcers
    • Reactivation factors: bacterial infection, hormonal changes, environmental stress
    • HSV-1 infects epithelial cells, spreads to sensory neurons, and persists in a latent state in the sensory neurons

    Latency-Associated Transcripts (LATs)

    • Expressed during latent infection, blocking transcription of lytic genes
    • Suppresses viral lytic gene expression, allowing the virus to maintain latency

    Cytoplasmic RNA Helicases

    • RIG-1 (Retinoic acid-inducible gene 1) and MDA5 (Melanoma differentiation-associated gene 5) are cytoplasmic RNA helicases that function as RNA sensors.
    • RIG-1 detects 5' triphosphate RNA (without 5' cap) in the cytoplasm, while MDA5 detects long dsRNA (and RNA without 5' cap).
    • RIG-1 and MDA5 contain tandem N-terminal CARD domains that are phosphorylated in uninfected cells, leading to an inactive conformation.

    Signaling Events

    • MAMP-PRR engagement leads to signaling events that activate transcription factors such as NFkB and the Interferon regulatory factors (IRFs), promoting the expression of IFNs and inflammatory cytokines.
    • PRRs undergo conformational change, exposing CARD domains that are dephosphorylated by specific phosphatases, leading to an active conformation.
    • In their active conformation, RIG-1 and MDA5 are translocated to bind with the mitochondrial antiviral signaling protein (MAVS).

    Protein Kinase R (PKR)

    • PKR is a sensor for viral dsRNA that inhibits cap-dependent translation by eIF2α (eukaryotic initiation factor).
    • PKR is activated by binding to viral dsRNA, leading to dimerization and autophosphorylation.
    • Activated PKR phosphorylates the α subunit of eIF-2, causing it to remain in an inactive GDP-bound form, leading to translation arrest.

    cGAS

    • Cyclic GMP-AMP synthase (cGAS) binds to viral dsDNA in the cytoplasm.
    • Following DNA binding, cGAS generates cyclic GMP-AMP (cGAMP), which binds and activates STING (located on the ER).

    Viral Evasion

    • Viruses evade RIG-1 and MDA5 responses through sequestration or modification of viral RNA ligands, manipulation of post-translational modifications, cleavage of RIG-1, MDA5, and MAVS, and sequestration or relocalization of RIG-1 and MDA5.
    • Viruses evade PKR responses by inhibiting the activation of PKR, using eIF2-independent translation mechanisms, activating protein phosphatase to remove the phosphorylated Protein, and activating RAS pathway to inhibit PKR.

    Viral Pathogenesis

    • Viral disease is a harmful abnormality resulting from viral infection of the host organism
    • A virus is pathogenic for a particular host if it can infect and cause signs of disease in that host
    • Viral virulence in intact animals should not be confused with cytopathogenicity for cultured cells

    Steps in Viral Pathogenesis

      1. Entry and primary replication
      1. Viral spread
      1. Cellular injury
      1. Host immune response
      1. Viral clearance or establishment of persistent infection
      1. Viral shedding

    Entry and Primary Infection

    • A virus must attach to and enter cells of one of the body surfaces (skin, respiratory tract, gastrointestinal tract, urogenital tract)
    • Respiratory tract is the most common portal of entry for viruses into the human body
    • Most respiratory tract infections occur through inhalation of aerosolized droplets or particles containing viruses

    Respiratory Tract

    • Upper respiratory tract (URT): lined with cilia and mucus-producing goblet cells
    • Lower respiratory tract (LRT): smaller aerosolized particles or liquids can travel into the lungs, where gas exchange occurs
    • Alveoli of the lungs contain alveolar macrophages and lack ciliated cells

    Gastrointestinal Tract

    • A hollow tube stretching from the oral cavity to the anus
    • Small intestine has finger-like projections called villi that increase the surface area of the epithelium

    Urogenital Tract

    • Refers to the organs involved in reproduction
    • Viruses can be transmitted via the genital tract through sexual activity or breaks in the genital epithelium
    • Examples: human papillomavirus (HPV), hepatitis B virus (HBV), human immunodeficiency virus (HIV)

    Skin

    • Composed of two layers of tissue: epidermis and dermis
    • Viruses that replicate in the epidermis, such as HPV, can gain access through small cuts or abrasions in the skin

    Placenta and Congenital Infections

    • Congenital infections occur when a mother infects a fetus before birth
    • Occur via vertical transmission (generational transmission of viruses from parents to their offspring)
    • Can lead to long-term persistence of the virus within the child

    Viral Spread

    • Tropism determines the pattern of systemic illness produced during a viral infection
    • Factors affecting viral tropism: many viruses produce disease at sites distant from their point of entry
    • Mechanisms of viral spread vary, but the most common route is via the bloodstream or lymphatics
    • Presence of virus in the blood is called viremia

    Cell Injury and Clinical Illness

    • Destruction of virus-infected cells in target tissues and physiological immune response contribute to disease development
    • Clinical illness is an insensitive indicator of viral infection; inapparent infections by viruses are very common

    Host Defense/ Recovery from Infection

    • Innate (nonspecific) immune response: physical barriers, anatomical barriers, epithelial and phagocytic enzymes, phagocytes, and inflammation-related serum proteins
    • Adaptive immune response (acquired/specific): carried out by lymphocytes (B cells, T cells) and humoral and cell-mediated immunity

    Viral Shedding

    • Pertains to the shedding of infectious virus into the environment
    • Last stage in viral pathogenesis
    • Occurs from the body surfaces involved in viral entry and at different stages of disease depending on the particular agent involved

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    Related Documents

    Lecture 7 - Viral-Host Interaction PDF
    Lecture 5: Virus-Host Interaction Patterns of Infection
    Host Immune Response Module 4B PDF

    Description

    This quiz covers general patterns of viral infection, including acute and persistent infection types. It explores virus particle production over time and the presence of symptoms.

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