Introduction to Human Viruses 2023 PDF

Introduction to human Viruses r Department of Microbiology Thursday, December 7, 2023 Learning Objectives • Definition of virus and viral structure • Steps in viral pathogenesis ✓ Entry and primary replication ✓ Spread and cell tropism ✓ Cell injury ✓ Recovery from infection or persistence ✓ Vira...

Introduction to human Viruses r Department of Microbiology Thursday, December 7, 2023 Learning Objectives • Definition of virus and viral structure • Steps in viral pathogenesis ✓ Entry and primary replication ✓ Spread and cell tropism ✓ Cell injury ✓ Recovery from infection or persistence ✓ Viral shedding • Outcomes of viral infections • Control of viral infection Thursday, December 7, 2023 Presentation title What are Viruses? Thursday, December 7, 2023 Presentation title What Are Viruses? Unique Class of Infectious Agent • Acellular, nonliving • Obligate intracellular parasites • Lack functional organelles for energy and macromolecule production Thursday, December 7, 2023 Presentation title What are Viruses? • Small 20-300 nm visualized using Electron microscopy • Simple structure composed of genetic material surrounded by one or several protective layers Thursday, December 7, 2023 Presentation title Host Range of Viruses Viruses can infect bacteria, plants, fungi, insects, animals and humans Virus host range can vary Narrow host range: Wide host range: Bacterial viruses - Influenza viruses Plant viruses (birds, animals and humans) Animal viruses - Rabies virus Human viruses (racoons, dogs, humans) Thursday, December 7, 2023 Presentation title Virus Structure • Virion is composed of ✓ the virus genome (nucleic acid) ✓ protein capsid (helical, icosahedral or complex structure) ✓ may have an envelope ✓ Viral enzymes and core proteins Thursday, December 7, 2023 Presentation title Virus structure Viral genomes: types of nucleic acids Thursday, December 7, 2023 Presentation title off Baltimore class include example Class I : ds DNA Adenoviridae Papovaviridae Poxviridae Herpesviridae adenoviruses Human papilloma virus Smallpox virus Herpes simplex virus Class II: ssDNA Parvoviridae Parvovirus B19 Class III : ds RNA Reoviridae Rotavirus Class IV: + ss RNA Picoviridae Caliciviridae Togaviridae Coronaviridae Polio virus Norwalk virus Rubella virus Class V: Orthomyxoviridae Paramyxoviridae Rhabdoviridae Influenza virus Parainfluenza virus Rabies virus Class VI: + ss RNA with RT Retroviridae HIV, HTLV Class VII: Hepadnaviridae Hepatitis B virus Thursday, December 7, 2023 - ss RNA ds DNA with RT Presentation title Virus Structure Viral capsid protection • Made of a number of structural units (capsomeres) 9 viral Thursday, December 7, 2023 of capsid Madeof numbers structure writs Presentation title of capsomered Viral Symmetry oh do Nucleic acid Protein subunits Icosahedral (cubic) helical 20 triangular faces 12 vertices 30 edges Thursday, December 7, 2023 Presentation title complex Thursday, December 7, 2023 Presentation title Viral Replication 1. Attachment (adsorption) 2. Penetration 3. Uncoating 4. Replication 5. Assembly 0 6. Release cell lysis/budding Thursday, December 7, 2023 Presentation title Steps in Viral Pathogenesis Thursday, December 7, 2023 Presentation title Viral Pathogenesis • Is the process by which viral infection leads to disease • Infection vs disease Mumps Thursday, December 7, 2023 Chicken Pox Measles Presentation title Herpes Facts About Viral Infections/ Disease • Many infections are subclinical/ asymptomatic • One virus can cause a number of diseases • One disease can be caused by a number of viruses • Outcome of viral infection depend on many factors including ✓The nature of the virus-host interaction ✓The host response to infection Thursday, December 7, 2023 Presentation title Determinants of Viral Disease in Wb Severity of the disease ✓ ✓ ✓ ✓ ✓ ✓ Type of disease caused depends on Cytopathic ability Immune status Virus inoculum size General health of the person Nutrition Genetic makeup of the person ✓ Age Thursday, December 7, 2023 ✓ ✓ ✓ ✓ ✓ ✓ Presentation title Viral pathogen (strain) Portal of entry* Access to target tissue Target tissue Tissue tropism (preference) of virus Permissiveness of cells for viral replication Box 49-1 Murray et al., Steps in Viral Pathogenesis • • • • • Entry and primary replication Spread and cellular tropism, Secondary replication in target tissue Cell injury and clinical manifestation Recovery vs persistence Viral shedding Thursday, December 7, 2023 Presentation title Viral Entry and Primary Replication Feco-oral / /airborne if SEES Thursday, December 7, 2023 Presentation title Viral Entry- Transmission Airborne/droplet • Human transmission via coughing, sneezing, vocalizing ✓ Inhaled droplets ✓ Common cold ✓ Chicken pox Faecal-oral • Ingestion contaminated food and water ✓ Hepatitis A ingests into ✓ Norwalk virus ✓ Polio virus Thursday, December 7, 2023 Ear Presentation title Viral Entry Direct inoculation • Blood transfusion, IV drug users, sharing razors and needle • Animal bites: dogs, cats, foxes and bats IT • Vector (of Arboviruses) – arthropod- borne ✓ Rabies ✓ arthropod vectors (insects) o Insect ingests virus from infected human or animal reservoir o Virus replicates in gut, spreads to salivary glands o Injected during next blood meal o Dengue fever Thursday, December 7, 2023 Presentation title Viral Entry Sexual contact • HIV • Herpes virus E Vertical transmission • Prenatal transmission- Rubella, CMV, Hepatitis B/C, HIV 5 • Intranatal- acquisition during birth – Herpes simplex virus E • Postnatal transmission- contact and breast feeding- CMV IH.is Thursday, December 7, 2023 Presentation title htramtTpostnatal DuringBreast feeding Primary Replication • Release of virus from first infected cells • determines whether infection remains local or SEES becomes systemic primary replication Em Determines wetherintention Becomes Local or systemic 20 Thursday, December 7, 2023 Presentation title Viral Replication LOCALIZED INFECTIONS: Virus: Primary Replication: Rhinoviruses Upper respiratory tract Rotaviruses Intestinal epithelium Papillomaviruses Epidermis SYSTEMIC INFECTIONS: Virus: Primary Replication: Secondary Replication: Enteroviruses (poliovirus) Intestinal epithelium Lymphoid tissues, CNS Herpesvirus (HSV types 1 and 2) Oropharynx or urogenital tract Lymphoid cells, peripheral nervous system, CNS Rabies virus Muscle cells and connective tissue CNS ? http://www.bact.wisc.edu/themicrobialworld/ViralDisease.html Thursday, December 7, 2023 Presentation title Spread and Cellular Tropism • Mechanisms for spread of viruses throughout the host: • The bloodstream • The nervous system • The lymphatics Thursday, December 7, 2023 Presentation title Spread and Cellular Tropism p infectivirus • Virions in blood from primary replication cause primary viraemia prescenceofvirus in Blood • After spread and further replication, secondary viraemia (higher concentration) • Viraemia may be short or long (e.g. hep B) • Concentration depends on rate of synthesis • Viraemia useful for: ✓ Diagnostics ✓ Source of virus spread Thursday, December 7, 2023 Presentation title 041 Spread and Cellular Tropism 1 58 • Most viruses preferentially infect and replicate in certain tissues and not others • The selectivity of productive infection is TROPISM • Factors ✓ Cellular receptors iii ✓ Host cellular proteases ✓ Temperature of replication Thursday, December 7, 2023 Presentation title Spread and Cellular Tropism • pH lability • Cellular transcription factors • Anatomic barriers: cells must be physically accessible to the virus • Local intrinsic and innate immune defenses • Antibody and cellular immune response Eventual outcome depends on balance between: Clearance by host vs. persistence by virus Thursday, December 7, 2023 Presentation title Host Defences to Viral Infection • Natural Barriers of the Body • Host Immunity Thursday, December 7, 2023 ✓ Innate response (‘nonspecific’) ✓ Adaptive (acquired) response (specific) Presentation title The Course of a Typical Acute Infection Thursday, December 7, 2023 Presentation title Cell injury and Clinical Manifestation Manifestation of viral diseases is combination of direct viral cytopathogenicity, and host immune response Thursday, December 7, 2023 Presentation title Shedding: Viral Shedding • Release of infectious virus from infected host • Localized infection ✓ Shedding may occur from primary replication site through a body opening • If systemic infection ✓ Potential for shedding to occur at other sites • Shedding of high concentrations of virus may facilitate transmission Thursday, December 7, 2023 Presentation title Transmission to New Host • Virus survives by transmission between susceptible hosts • Types of transmission ✓ Horizontal (most common) ✓ Vertical (parent to offspring) • Viruses may be restricted to one species, or have insect vector, or be shared between animals and humans (zoonoses) Thursday, December 7, 2023 Presentation title Outcome of Viral Infection Thursday, December 7, 2023 Presentation title Outcomes of Viral Infection 1. Failed infection - abortive 2. Lytic: – cytolytic/cytocidal infection resulting in host cell death 3. Non-lytic productive infection 4. Persistent ✓ Chronic - carrier of virus 6✓ Latent/Subclinical - presence of viral genome with no active replication, reactivation is possible ✓ Transforming (Oncogenesis) ✓ Slow infection Thursday, December 7, 2023 Presentation title Outcomes of Viral Infection Thursday, December 7, 2023 Presentation title Importance of Persistent Infections • May Be Reactivated And Cause Episodes Of Disease • May Be Associated With Virus-induced Immunopathological Disease • May Lead To Neoplasia • Persistence In A Population • If A Latent Genome Is Not Replicating, Virus May Not Be Accessible To Antiviral Agents Or Immune Response Thursday, December 7, 2023 Presentation title Control of Viral Infection Thursday, December 7, 2023 Presentation title Control of Viral Infection I. Vaccination II. Antivirals III. Education Thursday, December 7, 2023 Presentation title Control of Viral Infection Vaccination • Primes the adaptive immune system • Types: ✓ Live attenuated ✓ Killed inactivated vaccine ✓ Subunit vaccine ✓ Recombinant vector vaccine……. • Importance: lack of effective treatment Thursday, December 7, 2023 Presentation title Vaccine Success • Smallpox (variola virus) 4 ✓ Worldwide eradication • Polio (enterovirus) ✓ Eliminated in many developed countries • Childhood immunization schedules ✓ Huge decrease in infant mortality http://www.immunise.health.gov.au/internet/immunise /publishing.nsf/Content/nips Thursday, December 7, 2023 Presentation title Control of Viral Infection Antiviral Agents: • Problematic ✓ Because viruses replicate intracellularly using host cell components • Targets must be virus-specific ✓ To avoid damage to the host - selective toxicity Thursday, December 7, 2023 Presentation title Control of Viral Infection Antiviral Agents: • Examples: ✓ Attachment inhibitors: eg. Maraviroc ✓ Fusion inhibitor: e.g. Enfuvirtide ✓ Inhibitors of uncoating: eg. Amantadine ✓ Viral polymerase inhibitors eg. Acyclovir ✓ Interferon Thursday, December 7, 2023 Presentation title Summary • Viruses are small infectious agents with simple structure • Viral pathogenesis is the process by which viral infection leads to disease • Outcome of a viral infection is determined by ✓The nature of the virus-host interaction ✓The host response to infection • The outcomes of viral infection: ✓Abortive ✓Lytic ✓Non lytic ✓Persistent • Viral infections can be prevented/treated with vaccination and antivirals Thursday, December 7, 2023 Presentation title References • Goering et al., Mims Medical Microbiology, 5th edition, Chapters 3 and parts of 15, 16, 17 • Murray et al., Medical Microbiology, 5th edition, Chapters 49 and 50 • Jawetz et al., Medical microbiology Thursday, December 7, 2023 Presentation title