Lecture+7_+Ch+30.1-30.2+Pathogenesis++and+Control+of+Viral+Diseases.pdf

Chapter 30.1-30.2: Pathogenesis and Control of Viral Diseases Twenty-Eighth Edition Jawetz, Melnick, & Adelberg’s Medical Microbiology, Twenty-Eighth Edition 30.1: Principles of Viral Diseases Viral pathogenesis: occur...

Chapter 30.1-30.2: Pathogenesis and Control of Viral Diseases Twenty-Eighth Edition Jawetz, Melnick, & Adelberg’s Medical Microbiology, Twenty-Eighth Edition 30.1: Principles of Viral Diseases Viral pathogenesis: occurs when a virus infects a cell and cause cellular changes Disease pathogenesis: the subset of events during an infection that results in disease manifestation in the host Local infection vs. Systemic © McGraw-Hill Education, 2019 30.2.: Pathogenesis Of Viral Diseases Steps in viral Pathogenesis: 1. Entry & Primary Replication 2. Viral Spread and Cell Tropism 3. Cell Injury and Clinical Illness 4. Recovery from Infection © McGraw-Hill Education, 2019 30.2.: Pathogenesis Of Viral Diseases Steps in viral Pathogenesis: 1. Entry & Primary Replication Viral infections starts once virus has attached and entered a body surface: skin, respiratory tract, gastrointestinal tract, urogenital tract, or conjunctiva Most enter through the mucosa of the respiratory tract or gastrointestinal tract Note: some enter directly into the bloodstream via skin wound, needles, blood transfusion, insects. © McGraw-Hill Education, 2019 Common routes in Humans © McGraw-Hill Education, 2019 © McGraw-Hill Education, 2019 30.2: Pathogenesis Of Viral Diseases 2.- Viral Spread and Cell Tropism Viruses vary in where they can spread in the body Other viruses can spread to distant sites and cause additional disease manifestations © McGraw-Hill Education, 2019 30.2: Pathogenesis Of Viral Diseases a) Mechanisms of viral spread varies Mainly spread via the bloodstream or lymphatic system Virus in the blood = _________ Viruses may replicate within the cells they use to spread (EBV replicates in white blood cells as it moves through lymphatic system). Some viruses may travel as far as the brain, along neuronal axons (rabies) or cause latent infections this way (HSV). © McGraw-Hill Education, 2019  30.2: Pathogenesis Of Viral Diseases 3. Cell Injury and Clinical Illness Disease often stems from: host killing host cells of the targeted tissue or cell lysis. Note some tissue can rapidly regenerate after damage (intestinal epithelium) and recover normal function. General symptoms = cytokine production from the host, not the virus. Zika virus infection and microcephaly in Vietnam, Moi, Meng Ling et al.,The Lancet Infectious Diseases, Volume 17, Issue 8, 805 - 806 © McGraw-Hill Education, 2019 30.2: Pathogenesis Of Viral Diseases 4. Recovery from Infection Host will either: Succumb Recover Establish chronic infection Recovery mechanisms- innate and adaptive immune systems of host: Interferon (IFN) & other cytokines. Humoral and cell mediated immunity. Other host defense factors. © McGraw-Hill Education, 2019 30.2: Pathogenesis Of Viral Diseases 4. Recovery from Infection Genetics of host is thought to contribute to host susceptibility, but exact genes have not been determined for most infections Acute infections: recovery associated with viral clearance and viral-specific antibody production Chronic infections: more complex and depend on both viral factors and host immune factors. May also depend on viruses' ability to enter latency © McGraw-Hill Education, 2019 30.2: Pathogenesis Of Viral Diseases 5. Virus Shedding Stage when host is infectious to other hosts Last stage of pathogenesis Necessary for virus to stay within a population it infects Possible to have a dead- end host (rabies)- no shedding period © McGraw-Hill Education, 2019 30.2: Pathogenesis Of Viral Diseases - Host Immune Response in General - Specific and nonspecific A. Innate Immune Response Most prominent factor: cytokines (IFNs) among the innate immune function Main function of this response is to inhibit viral growth, while inducing a more specific immune response © McGraw-Hill Education, 2019 30.2: Pathogenesis Of Viral Diseases A. Innate Immune Response IFNs: host-coded proteins from a large cytokine family → regulate humoral and cell immunity → stop viral replication. Made fast (within hours) once the virus is detected. Multiple types of IFNs- 3 general groups: 1. IFN-α 2. IFN-β 3. IFN-γ Figure 1: Overview of the IFN pathway and viral- counteracting strategies. | Nature Reviews Immunology © McGraw-Hill Education, 2019  A. Innate Immune Response IFN-α and IFN-β (viral IFNs) IFN-γ (mitogen stimulation) RNA viruses are stronger inducers of IFN than DNA viruses Specific viruses have mechanisms to block IFN activity on their replication process and other immune pathways Ex: herpes, hepatitis C, rotavirus, etc. Viral respiratory infection © McGraw-Hill Education, 2019 © McGraw-Hill Education, 2019 30.2: Pathogenesis Of Viral Diseases How IFNs work IFN secreted binds cell receptors to start making other proteins that will inhibit replication (antiviral state) Multiple pathways involved 1. dsRNA-dependent protein kinase (PKR)- phosphorylates & inactivates cell initiation factor (elF-2) → stopping initiation complex in viral protein synthesis 2. Oligonucleotide synthetase (2-5A) → activates cell endonuclease to degrade mRNA 3. Phosphodiesterase → inhibits peptide elongation 4. Nitric oxide synthetase → induced by IFN-γ in macrophages © McGraw-Hill Education, 2019  30.2: Pathogenesis Of Viral Diseases B. Adaptive Immune Response: Humoral and cellular response Lymphocytes response: Proteins made by the virus are targets of immune response Cells infected by a virus can be lysed by cytotoxic T lymphocytes through recognition of viral polypeptides cell's surface © McGraw-Hill Education, 2019 Humoral Immunity- mainly involve B cells in blood and lymph Prevention of host being infected by virus again Neutralizing antibody directed against capsid proteins stop initial infection (attachment, entry, uncoating) Secretory IgA antibody protects against infection of viruses via respiratory or gastrointestinal tracts 11.5A: Humoral Immune Response - Biology LibreTexts © McGraw-Hill Education, 2019 Other immune function things to note Similar strains exacerbate subsequent infections (dengue hemorrhagic fever can develop if previous infection of another dengue serotype because of intense host reaction) Development of autoantibodies via molecular mimicry can also occur post immune response. Host may experience postinfectious autoimmune disease (Guillain-Barre syndrome after measles) © McGraw-Hill Education, 2019 30.2: Pathogenesis Of Viral Diseases Overview of Acute Viral Respiratory Infections The most frequent way virus cause infection- via droplets entering the respiratory tract Virus overcomes host immune deffences (mucus, cilliary action, lymphoid cells, alveolar macrophages, IgA) Most remain localized, some can spread (chicken pox, rubella) Definitive diagnosis requires isolation of the virus, identification of genes, or antibody titer change © McGraw-Hill Education, 2019 Viral infections of the Respiratory Tract © McGraw-Hill Education, 2019 30.2: Pathogenesis Of Viral Diseases Overview of Viral Infections of the Gastrointestinal Tract If virus initiates infection in the alimentary tract, it can survive harsh elements (bile salts, and acid) Acute gastroenteritis (short-term infection) symptoms range: watery stool, febrile illness, vomiting, systemic manifestations) Mainly caused by: rotavirus & norovirus Some viruses may infect this area, but are asymptomatic regarding intestinal symptoms (coronaviruses, enteroviruses, and adenoviruses) © McGraw-Hill Education, 2019 30.2: Pathogenesis Of Viral Diseases Overview of Viral Skin Infections Breach happens via: skin abrasions, bites of insects, injections via blood transfusion, needles, etc. Most spread to other sites, unless virus specifically infects epidermal cells Viruses that infect deeper dermis have a higher chance of causing systemic infections © McGraw-Hill Education, 2019  Skin Infections Types of lesions: 1. Macules: flat with local dilation of blood 2. Papules: elevated 3. Vesicles: occur in epidermis becomes focally detached 4. Pustules : if inflammatory reaction delivers polymorphonuclear leukocytes to lesion. 5. Hemorrhagic and Petechial rash occur is disruption to dermal vessels © McGraw-Hill Education, 2019 Description of Skin Lesions - Dermatologic Disorders - Merck Manual Professional Edition (merckmanuals.com)  30.2: Pathogenesis Of Viral Diseases Overview of Viral Infections of the Central Nervous System Viruses gain access to the brain 2 routes: 1. Bloodstream (hematogenous) Occurs: growth through endothelium of small cerebral vessels, passive transport a, passage via choroid plexus to cerebral spinal fluid (CSF), transport by infected immune cells Once blood-brain barrier is breached, more extensive spreading can happen Tends to be a correlation between level of viremia and neuroinvasive 12.1 Basic Structure and Function of the Nervous System - Anatomy and Physiology 2e | OpenStax © McGraw-Hill Education, 2019 Overview of Viral Infections of the Central Nervous System 2. Peripheral nerve fibers (neuronal spread) -Sensory nerve endings or motor endings are how virus gain access to PNS -Move further via axons through endoneural spaces or Schwann cell infections (herpesviruses travel in axons to reach dorsal root ganglia) Many viruses (ex herpes, flavivirus, etc.) can infect the CNS and cause meningitis, encephalitis, or both © McGraw-Hill Education, 2019 30.2: Pathogenesis Of Viral Diseases Overview of Congenital Viral Infections 3 principles involved in causing congenital defects: 1. Ability for virus to infect pregnant person and transmit to fetus 2. Stage of gestation when infection occurs 3. Ability of virus to directly infect the fetus and cause damage or indirectly by infecting the mother Primary viruses responsible: Rubella CMV Others include: herpes simplex, varicella-zoster, hepatitis B, etc. © McGraw-Hill Education, 2019  30.2: Pathogenesis Of Viral Diseases Diagnosis of Viral Infections Rapid antigen detection (uses specific monoclonal antibodies for detection) Nucleic acid or PCR tests (probes and primers to detect) Virus culture and serological tests for specific antibody response (can be slow) © McGraw-Hill Education, 2019