Introduction to Viruses 1 PDF Fall 2024

NURS: 201 Introduction to Viruses 1 Department of Microbiology, Immunology & Pharmacology Makeda Matthew-Bernard [email protected] https://www.nationalgeographic.com/magazine/article/why-werent-we-ready-for-this-virus  Learning Objectives 1. Define a virus and de...

NURS: 201 Introduction to Viruses 1 Department of Microbiology, Immunology & Pharmacology Makeda Matthew-Bernard [email protected] https://www.nationalgeographic.com/magazine/article/why-werent-we-ready-for-this-virus  Learning Objectives 1. Define a virus and describe its unique features 2. Explain the essential components of a virus and discuss their functions 3. Describe a capsid and explain how capsid structure can be utilized for the classification of viruses 4. Discuss the functions of the viral envelope and compare and contrast unique features of enveloped and non-enveloped (naked) viruses 5. Describe the various methods of classification of viruses 6. Characterize each of the stages of the viral replication cycle and describe what is occurring at each stage 7. Define a bacteriophage and discuss its unique features and mechanism of replication 8. Discuss latent and oncogenic viruses 9. Discuss how animal viruses can be grown in a laboratory and the various techniques utilized for their quantification 10. Describe the three major groups of subviral entities (viroids, satellite, prions) and identify each when provided with a description of their features 2  Outline What are viruses Properties of viruses Virus structure Type of viruses Viral genome Virus classification (Baltimore and ICCV) Naming viruses Viral host tropism 3  4 https://courses.lumenlearning.com/suny-wmopen-biology2/chapter/prevention-and-treatment-of-viral-infections/  Viruses What are they? non-cellular organisms (acellular microbes or infectious particles) Are they alive? Outside of the host cell behave as non-living structures, called virions Inside of host cell behave as living organisms, called viruses Viruses that infect humans and animals are collectively called animal viruses 5  Viruses Said to have five properties distinguishing them from living cells: 1. Possess either DNA or RNA, unlike living cells, which possess both. 2. Unable to replicate (multiply) independently; the viral nucleic acid directs their replication once it has been introduced into a host cell. 3. Unlike cells, they do not divide by binary fission, mitosis, or meiosis. 4. They lack the genes and enzymes necessary for energy production. 5. They depend on the ribosomes, enzymes, and metabolites (“building blocks”) of the host cell for protein and nucleic acid production. 6  Viruses - Size Viruses are “invisible” by light microscopy An electron microscope is required to visual most viruses Viruses can range in size from about 20 nm to 400 nm [e.g., parvovirus B19 (20 nm), smallpox (400 nm)] Viruses larger than poxviruses have been isolated (e.g, 7 http://ebola--history-facts-perspective.weebly.com/how-big-are-pathogens.html mimivirus) https://www.livescience.com/82-huge-virus-defies-classification.html Viruses can infect any living organism Animals Plants Bacteria Fungi Protists 8 https://biologicalsciences.blogs.bristol.ac.uk/2019/12/09/our-deep-origins-deciphering-the-earliest-branches-on-the-tree-of-life/  Viruses are classified by the following characteristics Type of genetic material (either DNA or RNA) Whether the virus nucleic acid is single-stranded or double-stranded Type of nucleic acid the virus has (positive-sense or negative-sense) Shape of the capsid Number of capsomeres Size of the capsid Presence or absence of an envelope Type of host that it infects Type of disease it produces Target cell Immunologic or antigenic properties 9  10 Virus Structure Components: Genome DNA or RNA Capsid Genome + Capsid = Nucleocapsid Virus specific glycoproteins Some may have an envelope https://www.ucir.org/therapies/oncolytic-viruses Virus Capsid The capsid serves to protect the nucleic acid genome Consist of single or several different subunits (capsomeres) that are held together by non-covalent, reversible hydrophobic or hydrogen bonds Capsomeres are compactly folded proteins that vary in size (50-350 aa) that have identifiable domains and fold only one way 11 Virus Capsid Capsid proteins have various functions: Define tissue or species-specific transmission by interaction with host receptors to facilitate the host cell entry Interact with the viral nucleic acid for packaging/ assembling of the virus Enzymatic functions Assist in viral and/or host gene regulation Evade/block host immune system and other functions 12  Icosahedral Capsid Icosahedral symmetry – is any polyhedron having 20 triangular faces. Few proteins assemble in basic protomers The protomers assemble into pentamers The pentamers assemble into icosahedral virion particles, e.g., poliovirus © 2013 Pearson Education, Inc. ; Brock Biology of Microorganisms (13th Edition) Elsevier: Medical Microbiology, 8th Edition: Murray et al. 13 © 2023 McGraw Hill. Helical Capsid Helical capsids appear as rod-like, filamentous structures (may be rigid or flexible depending on the specific virus). Capsomers bind to the viral genome in a regular fashion. No empty helical capsids can form. Helical capsids are “open-ended” All known examples of animal viruses with helical symmetry contain RNA genomes and have flexible nucleocapsids wound into a ball and surrounded by an envelope, except Rhabdoviruses. 14  Complex Capsid Some viruses do not exhibit cubic or helical symmetry -they are complex. e.g. Poxviruses 15  Viral Envelope Viral envelope is a lipoprotein membrane derived from the host membrane and can be: Cell plasma membrane (HIV; most of the enveloped viruses) Nuclear or other internal (endoplasmic reticulum) membranes (herpesviruses) The viral envelope is poor in host cell proteins, but rich in virus- specific glycoproteins-viral attachment protein (VAP) 16 Types of viruses 17 https://www.bioprocessintl.com/viral-clearance/detection-and-clearance-of-viruses-in-the-biopharmaceutical-industry  Enveloped viruses Have an envelope which protects the capsid Enveloped viruses are sensitive to inactivation by organic solvents (alcohol, chloroform, ether, etc.) detergents, drying, acid, and heat. They are usually transmitted by secretions, large droplets, blood, or sexual contact e.g., measles virus Enveloped viruses are usually spherical or pleomorphic in shape except for: 1. Rhabdovirus (rabies) bullet-shaped 2. Poxvirus (smallpox) complex shape http://www.naro.affrc.go.jp/english/niah/em/files/sparrow-pox-em.jpg 18 © 2023 McGraw Hill. Non-enveloped (naked) viruses Viral nucleocapsid is naked Non-enveloped (naked) viruses are tough and relatively resistant to inactivation by organic solvents (alcohol, chloroform, ether, etc.) detergents, drying, acid, and heat. They are usually transmitted by fecal/oral route, fomites, or small droplets They are released from infected cells by lysis. e.g., poliovirus, adenovirus © 2023 McGraw Hill. 19 https://wshoms.co.uk/the-history-of-polio/ https://www.researchgate.net/publication/11982046_Activation_of_Innate_Immunity_in_Nonhuman_Primates_Following_Intraportal_Administration_of_Adenoviral_Vectors/figures?lo=1 Bacteriophage Bacterial viruses are known as bacteriophages (or just phages) Infect bacteria Structure Head – nucleic acid and protein Tail and contractive sheath Tail fibers and tail pins Base / end plate Foundations of microbiology 10th edition 20 Copyright © 2019 Wolters Kluwer  Viral Structure Baltimore D (2023) Turning RNA Into DNA: The Discovery That Revolutionized Biology and Biotechnology. Front. Young Minds. 11:1080663. doi: 10.3389/frym.2023.1080663 21 Viral Genome Understanding viral genome means understanding different modes of genome replication and viral propagation Genome replication is directly linked to viral classification and phylogenetic relationship One convergent point for all viruses is that they all need to go through mRNA (+) strand synthesis. positive (+) nucleic acid (DNA or RNA) is the gene coding sequence negative (-) nucleic acid (DNA or RNA) is the complementary strand to the gene-coding mRNA (template strand) 22  Positive vs. Negative Strands The concept of positive and negative strands is found mostly in virology because in higher organisms either strand can be coding a gene. Within the host cell, single-stranded positive-sense RNA functions as messenger RNA (mRNA) Single-stranded negative-sense RNA serves as a template for the production of mRNA 23  Viral Genome Nucleic acid represents the viral genome: DNA-based genomes are always presented by a single molecule, either dsDNA or ssDNA (positive or negative) RNA-based genomes exist as either single or several molecules When multiple RNA nucleic acids are presented, the genome is either segmented or diploid dsRNA: Reoviruses (segmented genome) ssRNA positive (+): Retroviruses (diploid genome) negative (–): Orthomyxoviruses (segmented genome) 24 Naming Viruses Named after the disease associated with the virus Poxvirus (smallpox), Hepatitis viruses (different viruses all affecting the liver) Reoviruses (respiratory, enteric, orphan) Human immunodeficiency virus (immune system) Named after the type of cytopathology they cause Respiratory syncytial virus (syncytium - fusion of infected cells), Cytomegalovirus (Greek cyto - "cell", and megalo - "large") Named after places or people Rift Valley Fever virus (Rift valley, Kenya) Epstein-Barr virus (also known as HHV-4) 25 Naming Viruses Named after the site of isolation Adenovirus (adenoids - an enlarged mass of lymphoid tissue in the upper pharynx), Enterovirus (enteric) Rhinovirus (from Greek - rhinos means “nose”) Named after the viral biochemical features Retrovirus (retro - “reverse”) Picornavirus (pico - “small”, RNA - rna) Togavirus (toga - “mantle”) 26  Virus Classification (ICTV) A universal system for classifying viruses and a unified taxonomy, has been established by the International Committee on Taxonomy of Viruses (ICTV) since 1966. The system makes use of a series of ranked taxons (order/family/sub-family/genus/species). Order Order: Mononegavirales Family (-idae) Family: Paramyxoviridae Subfamily (-inae) Subfamily: Paramyxovirinae Genus (-virus) Genus: Morbillivirus Species Species: Measles virus [isolates, strains] 27  Baltimore Classification (defined in 1971) Modified from: © 2013 Pearson Education, Inc. ; Brock Biology of Microorganisms (13th Edition) 28  Viral Hosts and Tropism Viruses have a well-defined range of hosts that can be either limited or include a broad range of susceptible species The viral “tropism” might be limited to a single organ, tissue, specialized cell type, or range of different organs and tissues Tropism is defined by a few factors: The viral glycoproteins (VAP) integrated into the outer coat: either the capsid or the envelope that target receptors are acting as doors on the surface of the host cells (susceptibility) The presence of transcription factors allowing expression of viral genes The presence of cell enzyme pathways to produce viral proteins is known as “permissivity” https://www.labxchange.org/library/items/lb:LabXchange:a8d89b8f:lx_image:1 29  Viral Hosts and Tropism It all boils down to the receptors Influenza A virus attaches to sialic acid residues on the surface of mucosal cells Cells of the respiratory tract are rich in sialic acid –thus influenza infection begins in the respiratory tract 30