Medical Virology Lecture Notes PDF

Al-Turath University /College of Pharmacy nd nd Microbiology II-2 semester/2 year students (2023/2024) Assist. Prof. Dr. Shaymaa Abdalwahed Medical Virology Lec 1 Definition ► Virology is the bioscience for study of viral nature, and the relationship between viruses and hosts. Viruses often cause se...

Al-Turath University /College of Pharmacy nd nd Microbiology II-2 semester/2 year students (2023/2024) Assist. Prof. Dr. Shaymaa Abdalwahed Medical Virology Lec 1 Definition ► Virology is the bioscience for study of viral nature, and the relationship between viruses and hosts. Viruses often cause serious diseases, relate to some cancers and congenital deformities, also can be used as tool for genetic engineering. History ► Oreginated 1000 yrs BC in China when dried crusts from smallpox lesions isolated from cured patients where inhaled or inoculated of the pus into a scratch in the arm of a child. They coined/invented the first concept of Variolation. ►Dmitri Ivanovski is credited as the original discoverer of viruses and a founder of the field of virology. Today, we can see viruses using electron microscopes. ►Viruses are distinct biological entities; however, their evolutionary origin is still a matter of speculation. In terms of taxonomy, they are not included in the tree of life because they are acellular (not consisting of cells). In order to survive and reproduce, viruses must infect a cellular host, making them obligate intracellular parasites. The genome of a virus enters a host cell and directs the production of the viral components, proteins and nucleic acids, needed to form new virus particles called virions. New virions are made in the host cell by assembly of viral components. The new virions transport the viral genome to another host cell to carry out another round of infection. History ► Viral infections have been recorded unknowingly from the beginning of recorded history. ► Plant scientists had isolated material that passed through a low pore filter that was infectious to tobacco plants. ► The twentieth century saw the discovery of bacteriophage, viruses that attack bacteria, and 1 the use of such bacteriophage to launch/start studies of molecular biology, and DNA and RNA structure. Definition Of Virus ❑ Virus come from the Latin for poison or slimy matter. ❑ Viruses may be defined as an extremely small piece of organic material that causes disease in humans, animals, and plants. ❑ Virus is acellular organisms whose genomes consist of nucleic acid, and which obligately replicate inside host cells using host metabolic machinery and ribosomes to form a pool of components which assemble into particles called Virions, which serve to protect the genome and to transfer it to other cells. Viral Properties or the Characteristics of viruses are: 1 Viruses are inert (nucleoprotein) filterable Agents. 2 Viruses are obligate intracellular parasites with host and cell-type specificity. 3 Viruses cannot make energy or proteins independent of a host cell. 4 Viral genome are RNA or DNA but not both. 5 Viruses have a naked capsid or envelope with attached proteins. 6 Viruses do not have the genetic capability to multiply by division. 7 Viruses are non-living entities (acellular pathogens). It is Infectious. Consequences of viral properties: Viruses are non-living. Viruses must be infectious to endure/survive in nature. Viruses must be able to use host cell processes to produce their components (viral messenger mRNA, protein, and identical copies of the genome). Viruses must encode any required processes not provided by the cell. Viral components must self-assemble. Genome is surrounded by a protein capsid and, in some cases, a phospholipid membrane studded/covered with viral glycoproteins. Lack genes for many products needed for successful reproduction, requiring exploitation (use or abuse) of host-cell genomes to reproduce. 2 Challenges the way we define life 􀀀 The universe of viruses is rich in diversity. 􀀀 Viruses vary greatly in structure, genome organization and expression, and strategies of replication and transmission. 􀀀 The host range for a given virus may be broad or extremely limited. 􀀀 Viruses are known to infect unicellular organisms such as mycoplasmas, bacteria, and algae and all higher plants and animals. 􀀀 Viruses do not respire, nor do they display irritability, they do not move, they do not grow, they do most certainly reproduce, and may adapt to new hosts. Measuring the Sizes of Viruses Small size and the ability to pass through filters that hold back bacteria are classic, some bacteria may be smaller than the largest viruses. Electron microscopy (EM) (the two most common type of EM are transmission electron microscopes (TEMs) and scan electron microscopes (SEMs) The resolution is 5nm (1nm = 10-9 m) X-ray crystallography is used to determine the atomic structure of viruses (visualizing virus 3D structures). Size of Viruses A small virus has a diameter of about 18-26 nm. Having only 30 capsomeres. ✓ Parvovirus and Picornavirus. A large virus has a diameter of up to 230 nm by 400nm. (genome 130-360 kilobase (kb) in length) ✓ Poxviruses 3 Shape of Viruses: Spherical (Space vehicle shaped) (e.g. Human Immunodeficiency Virus (HIV)) Rod-shaped (e.g. Rudivirus) Brick-shaped (e.g. Poxviridae, Poxviruses) Tadpole-shaped (e.g. T bacteriophage) Bullet-shaped (e.g. Rhabdoviridae, Rabies) Filament (e.g. Filoviridae, Ebola virus) Origin of viruses: there are three hypothesis regarding the origin of viruses: 1. Regressive hypothesis. 2. Cellular origin hypothesis. 3. Coevolution hypothesis. 1. Regressive hypothesis ❑Viruses may have once been small cells that parasitised larger cells. ❑Over time, genes not required by their parasitism were lost. ❑The bacteria rickettsia and chlamydia are living cells that, like viruses, can reproduce only inside host cells. They lend/add support to this hypothesis, as their dependence on parasitism is likely to have caused the loss of genes that enabled them to survive outside a cell. 4 ❑This is also called the degeneracy hypothesis, or reduction hypothesis. ❑The regressive hypothesis did not explain why even the smallest of cellular parasites do not resemble viruses in any way. 2. Cellular origin hypothesis ❖Some viruses may have evolved from bits of DNA or RNA that "escaped" from the genes of a larger organism. ❖The escaped DNA could have come from: A. plasmids (pieces of naked DNA that can move between cells) B. transposons (molecules of DNA that replicate and move around to different positions within the genes of the cell). Once called "jumping genes", transposons are examples of mobile genetic elements and could be the origin of some viruses. ❖They were discovered by Barbara McClintock in 1950. ❖This is sometimes called the vagrancy hypothesis, or the escape hypothesis. ❖The escape hypothesis did not explain the complex capsids and other structures on virus particles. 3. Coevolution hypothesis This is also called the virus-first hypothesis and proposes that viruses may have evolved from complex molecules of protein and nucleic acid at the same time as cells first appeared on Earth and would have been dependent on cellular life for billions of years. The virus-first hypothesis contravened the definition of viruses in that they require host cells. Viroids are important pathogens of plants. Viroids are molecule of RNA that do not fit the definition of classic viruses because they lack a protein coat. They are smaller than a virus and consisting only of nucleic acid without a protein coat (do not code for proteins) but interact with the host cell and use the host machinery for their replication. Satellites virus may represent evolutionary intermediates of viroids and viruses. Viruses are now recognised as ancient and as having origins that pre-date the divergence of life into the three domains. This discovery has led modern virologists to reconsider and re-evaluate these three classical hypotheses. Prions are infectious protein molecules that do not contain nucleic acid (DNA or RNA). They are highly resistant to inactivation by heat, formaldehyde, and ultraviolet light that inactivate viruses. The prion protein is encoded by a single cellular gene. 5 Prion diseases, called “transmissible spongiform encephalopathies”, include scrapie in sheep, mad cow disease (bovine spongiform encephalopathy) in cattle. In humans, prionic diseases include Kuru, Creutzfeldt–Jakob disease. 􀀀Although prions are fundamentally different from viruses and viroids, their discovery gives credence to the theory that viruses could have evolved from self-replicating molecules. Structure of viruses Virion (virus particle) is the complete infectious unit of virus particle. It is structurally mature, extracellular virus particles. Virion is represents a virus in its extracellular phase. Virion is Function to transfer the viral nucleic acid from one cell to another. In some instances (eg, papillomaviruses, picornaviruses), the virion is identical with the nucleocapsid. In more complex virions (herpesviruses, orthomyxoviruses), this includes the nucleocapsid plus a surrounding envelope. To ensure survival of a virus, the virion must fulfill two roles: (1) protecting the genome from environmental damage, for example, from heat, desiccation/dryness, chemicals; and (2) facilitating the passage of the virus to the next host, that is, from the point of release from the original host, passage through the environment to the point of encountering/meeting a new host, followed by entry into the cells of the new host. Viral components: Nucleic acids, Capsid, Envelope, Glycoprotein. Viral core: Is the viral nucleic acid genome, found in the center of the virion, it is control the viral heredity and variation, responsible for the infectivity. Genome (Chemical Composition Of Viruses) The genome of a virus can be either DNA or RNA molecules (classification property). 6 Both DNA and RNA genomes can be either double-stranded (ds) or single-stranded (ss), linear or circular, as well as monopartite (all viral genes contained in a single molecule of nucleic acid) or multipartite (segmented) (viral genes distributed in multiple molecules or segments of nucleic acid). DNA-double stranded (ds): linear (single) or circular (single, multiple) Single stranded (ss) : linear (single) or circular (single, multiple) RNA- ss: segmented or non-segmented ss: polarity+(sense) or polarity –(non-sense) ds: linear (single, multiple) (only reovirus family) Single-stranded (ss) RNA genomes can be defined according to coding sense (also called polarity). If the genomic RNA is of the same sense as mRNA, that is, it can direct the synthesis of protein (i.e can immediately translated by host cell), it is said to be of positive-sense (also called plus sense). If, on the other hand, the genomic nucleotide sequence is complementary to that of mRNA, it is said to be negative-sense. Consequently, the genome of the virus cannot translate readily into the viral proteins. 7 In addition to the properties of the genome, the following properties have been used as a basis for the classification of viruses: 1. Virion morphology, including size, shape, type of symmetry. or absence of peplomers, and presence or absence of membranes. 2. Virus protein properties, including number, size, and functional activities of structural and nonstructural proteins, amino acid sequence, and modifications (glycosylation, phosphorylation). 3. Antigenic properties. 4. Biologic properties, including natural host range, mode of transmission, vector relationships, pathogenicity, tissue tropisms, and pathology. 5. Genome organization and replication, including gene order, number and position of open reading frames, strategy of replication (patterns of transcription, translation), and cellular sites (accumulation of proteins, virion assembly, virion release). 6. Virus genome properties, including type of nucleic acid (DNA or RNA), size of genome in kilobases (kb), strandedness (single or double), whether linear or circular, sense (positive, negative), segments (number, size), nucleotide sequence and GC-content (or guanine-cytosine content). 7. Physicochemical properties of the virion, including molecular mass, pH stability, thermal stability, and susceptibility to physical and chemical agents, especially ether and detergents. Viral Capsid The protein shell, or coat, that encloses the nucleic acid genome. Viral capsid is composed of repeated protein subunits known as capsomeres, which are made of one or more proteins known as the chemical subunit or structural subunit. Viral Capsid Functions: A. Protect the viral nucleic acid. B. Participate in the viral infection. C. Share the antigenicity. Capsomeres: Morphologic units seen in the electron microscope on the surface of icosahedral virus particles. Capsomeres represent clusters of polypeptides, but the morphologic units do not necessarily correspond to the chemically defined structural units (protomer). Defective virus: A virus particle that is functionally deficient in some aspect of replication. Envelope: A lipid-containing membrane that surrounds some virus particles. It is acquired during viral maturation by a budding process through a cellular membrane. Virus encoded glycoproteins are exposed These on theare surface of theprojections, envelope.orThese projections are called peplomers. Peplomers: the specific spikes, made of glycoproteins that stick out from the virus’s envelope. The essential components of infectious viral particles are nucleic acid (the genome) and protein. In addition, all enveloped viruses contain lipid in the envelope and carbohydrate in their glycoprotein peplomers (as well as that in the nucleic acid). 8 Nucleocapsid – The core of a virus particle consisting of the genome (nucleic acid) plus a complex of proteins. – Or : The protein–nucleic acid complex representing the packaged form of the viral genome. The term is commonly used in cases in which the nucleocapsid is a substructure of a more complex virus particle (Virion). – complex of proteins = Structural proteins +Non- Structural proteins (Enzymes &Nucleic acid binding proteins) Structural units: ❑ The basic protein building blocks of the coat. ❑ They are usually a collection of more than one nonidentical protein subunit. ❑ The structural unit is often referred to as a protomer. ❑ Capsomeres are individual proteins composed of protomers. Protomers make up capsomeres which form the capsid, a protein coat. Subunit: A single folded viral polypeptide chain. Types of Symmetry Of Nucleocapsid Viral architecture can be grouped into three types based on the arrangement of capsomeres and the morphology of the nucleocapsid subunits: 1.Helical symmetry, e.g. Orthomyxoviruses. 2. Cubic symmetry (Icosahedral), e.g. Adenoviruses 3. Complex structures, e.g. Poxviruses and Bacteriophage. 1. Helical symmetry: In cases of helical symmetry, protein subunits are bound in a periodic way to the viral nucleic acid, winding it into a helix. The filamentous viral nucleic acid–protein complex (nucleocapsid) is then coiled inside a lipidcontaining envelope. This arrangement results in rod-shaped or filamentous virions: These can be short and highly rigid, or long and very flexible. The genetic material, in general, single-stranded (ss) RNA, but ss DNA in some cases. 9 Example of Helical symmetry: California Encephalitis Virus, Coronavirus, Hantavirus, Influenza Virus (Flu Virus), Measles Virus (Rubeola), Mumps Virus, Parainfluenza Virus, Rabies Virus, Respiratory Syncytial Virus (RSV). 2. Cubic (Icosahedral) symmetry ❑ icosahedral is a solid figure with twenty plane faces, especially equilateral triangular ones. ❑ Most animal viruses are icosahedral or near-spherical with icosahedral symmetry. ❑ A regular icosahedron is the optimum way of forming a closed shell from identical sub-units. ❑ The icosahedron has 20 faces (each an equilateral triangle), 12 vertices, and fivefold, threefold, and twofold axes of rotational symmetry. ❑ Many viruses, such as rotavirus, have more than twelve capsomers and appear spherical but they retain this symmetry. ❑ Capsomers at the apices are surrounded by five other capsomers and are called pentons. ❑ Capsomers on the triangular faces are surrounded by six others and are called hexons. ❑ There are exactly 60 identical subunits on the surface of an icosahedron. ❑ To build a particle size adequate to encapsidate viral genomes, viral shells are composed of multiples of 60 structural units. 10 3. Complex Virus Structures ► A well known example is the tailed bacteriophages such as T4 bacteriophages. ► The head of these viruses is cubic with a triangulation number of 7. This is attached by a collar to a contractile tail with helical symmetry. ► Some virus particles do not exhibit simple cubic or helical symmetry but are more complicated in structure. ► Ex. poxviruses are brick shaped, with ridges on the external surface and a core and lateral bodies inside. Figure show the types of virus morphology. Virus (A) is a helical virus, where the capsoid has a helical shape that envelops the genomic material, virus (B) is icosahedral following cubic symmetry, (C) is a complex virus, namely a bacteriophage with a prolate capsid protecting the genomic material, and (D) is virus covered by a viral envelop. Naked viruses, or non-enveloped viruses, do not have a viral lipid envelope. They have only the capsid. This characteristic is the primary basis in distinguishing them from the enveloped viruses. Naked viruses pertain to those that only have nucleocapsid, which is a protein capsid that covers the genome of the virus. These viruses use their nucleocapsid to enter cells. 11 Properties of naked viruses: 1. Stable in hostile environment. 2. Not damaged by drying, acid, detergent, and heat (because they lack a lipid sheath, which when present can be disrupted by a disinfectant). 3. Released by lysis of host cells. 4. Can sustain in dry environment. 5. Can infect the GI tract and survive the acid and bile. 6. Can spread easily via hands, dust, fomites, etc. 7. Can stay dry and still retain infectivity. 8. Neutralizing mucosal and systemic antibodies are needed to control the establishment of infection. Naked viruses example are: Adeno-associated Virus (AAV), Adenovirus B19, Coxsackievirus A, Coxsackievirus -B, Echovirus, Hepatitis A Virus (HAV), Hepatitis E Virus (HEV), Norwalk Virus, rotavirus, Norovirus, parvovirus. (a)virions lacking envelopes=Naked viruses (b)virions having envelopes=Enveloped viruses Envelope viruses ❑It is a lipid-containing membrane that surrounds some viral particles. ❑It is acquired during viral maturation by a budding process through a cellular membrane, Viruses-encoded glycoproteins are exposed on the surface of the envelope. ❑Not all viruses have the envelope. Envelope viruses example: Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Human Immunodeficiency Virus (HIV), herpes simplex virus, parainfluenza virus, adenovirus, Hepatitis B Virus (HBV), Hepatitis C Virus (HCV). Viral Glycoproteins (attached to the envelope) Viral envelopes contain glycoproteins. In contrast to the lipids in viral membranes, which are derived from the host cell, the envelope glycoproteins are virus-encoded. However, the sugars added to viral glycoproteins often reflect the host cell in which the virus is grown. Function Viral Glycoproteins: 1▪ attach the virus particle to a target cell by interacting with a cellular receptor. 2▪ Involved in the membrane fusion step of infection. 3▪ The glycoproteins are also important viral antigens. 4▪ Involved in the interaction of the virus particle with neutralizing antibody. 12 Properties of enveloped viruses 1. Labile in dry, arid environment. 2. Damaged by drying, acid, detergent, and heat. 3. Pick up new cell membrane during multiplication. 4. Insert new virus-specific proteins after assembly. 5. Virus is released by budding. Consequences of Properties for enveloped viruses 1. Must stay moist. 2. Must not infect the GI tract for survival. 3. Must be transmitted in the protective, droplets, secretions, blood and body fluids. 4.Must reinfect another host cell to sustain. 5. Humoral and cell-mediated immunity are needed to control the infection. Enveloped 13 Differences between naked viruses and enveloped viruses Definition structure Virulence Host lysis Susceptibility to disinfectants sensitivity to heat and dryness Examples Naked Viruses Viruses without an envelope Nucleocapsid More virulent May cause host lysis upon exit Less susceptible to disinfectants Enveloped Viruses Viruses with an envelope on the exterior Nucleocapsid + Viral Envelope Less virulent Rarely; often leaves cells by budding off the host cell membrane More susceptible to disinfectants Resistant to heat and dryness Sensitive to heat and dryness Norovirus, parvovirus, HAV HIV, HBV, adenovirus, influenza virus Thank You 14