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Basic virology (a.3)
Viruses are small infectious agents that can cause diseases in humans. They replicate inside host cells by using the cell's resources. There are three main stages of viral replication: early, central, and final. In the early stage, viruses attach and enter cells. In the central stage, they produce mRNA, proteins, and genomic material. In the final stage, new virus particles assemble and are released. Viruses can mutate, allowing them to evolve and evade host immune responses. They also interact genetically with each other and their hosts. Viruses cause a wide range of human diseases and conditions, from common colds to cancers.
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Basic virology (a.3)
- 1. BASIC MEDICAL VIROLOGY LudhangPradipta Rizki MD., M.Biotech, Clinical Microbiologist Departement of Microbiology Faculty of Medicine UGM
- 2. BASIC MEDICAL VIROLOGY Virologyis 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. Concepts
- 3. Viruses are livingorganisms? BASIC MEDICAL VIROLOGY Question ?
- 4. The General Structureof Viruses Viruses not living organisms Basic Properties Cannot replicate independently Cannot survive long-term independently Contain no ribosomes (cannot synthesise protein)
- 5. The General Structureof Viruses Basic Properties
- 6. Size and Structure Virusesare much smaller (φ 20-300nm) than bacteria, fungi and protozoa Basic Properties Viruses structure is simple Nucleocapsid Protein shell (capsid) Many viruses also have an outer envelope Methods of Analysis use Electron microscopy (the resolution is 5 nm) and X-ray crystallography
- 7. Size and StructureBasic Properties
- 8. Size and StructureBasic Properties
- 9. Shape of VirusesBasic Properties Spherical Rod-shaped Brick-shaped Tadpole-shaped Bullet-shaped Filament
- 10. Shape of VirusesBasic Properties
- 11. Structure and Composition TheVirus particle called a virion Structure Virion consists of nucleocapsid with 2 components (the single or double stranded, linear, circular or segmented DNA or RNA genome) Virion with surrounding protein shell called the capsid
- 12. Capsid The capsid`s repeatingprotein units form structural units (Capsomeres) Structure Capsomers arranged with either helical or isocohedral symmetry, complex symmetrty Nucleocapsid of some human viruses is “naked”
- 13. Helical Nucleocapsids &Capsomeres Structure
- 14.
- 15. Chemical Composition ofViruses Viral Protein Structure Viral Nucleic Acid Viral Carbohydrate Viral Lipids
- 16. Chemical Composition ofViruses Structure
- 17. Composition of Viruses ViralNucleic Acids Structure Viral Protein and Viral enzymes Viral envelopes Viral core Viral core : The viral nucleic acid genome, in the center of the virion, Control the viral heredity and variation, responsible for the infectivity
- 18. Viral Nucleic AcidsStructure
- 19. Viral Envelopes Viral envelopesare lipoprotein and composed of an inner structural derived protein and an outer host cell derived lipid layer Structure 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
- 20. Viral Envelopes In additionthere are often projecting spikes of glycoprotein (Viral Attachment Proteins (VAPs) to host cells) Structure Not all viruses have the envelope, and viruses can be divided into 2 kinds: enveloped virus and naked virus
- 21.
- 22. Naked Capsid andEnveloped Virus Structure
- 23. Atypical viral-like agentsStructure Defective viruses Pseudovirions Viroids Prions
- 24. Atypical viral-like agentsStructure Defective viruses Pseudovirions Defective viruses (Hepatitis D) have viral protein but defective nucleic acid (by mutation or deletion) Cannot replicate without a helpervirus (Hepatitis B) • Viral DNA replaced by host-cell DNA which has fragmanted and been incorporated into the viral capsid • Can infect but of course cannot replicate
- 25. Atypical viral-like agentsStructure Viroids Prions Only single small molecule of RNA (subviral particles) No capsid or envelope How they replicate is unclear Can infect plants but not humans Prions a single glycoprotein with no detectable nucleic acid, yet replicate. The protein is encoded by a host cell gene, not viral gene The increase in numbers of prions infected in human nervous tissue (Cruetzfeldt-Jakob disease)
- 26. The Host Cell Abortive(no replication, no visible host cell effect, no disease) Cytolytic (cell death and virus dissemination then disease, then death or recovery of the host) Persistent Three major types of viral infection occurs: Latent No effect on the cell, but may re-activate (e.g.herpes) Productive Give chronic carriage or disease (e.g. hepatitis B) Transforming Producing tumours (e.g. EBV lymphomas)
- 27. The Host CellThreemajor types of viral infection occurs:
- 28. How Viruses areClassified and Named? Clasisification of Viruses Question ?
- 29. Clasisification of VirusesStructure
- 30. Clasisification of VirusesStructure
- 31.
- 32. Baltimore Clasisification Genome TheBaltimore classification based on the relationship of the viral genome to its mRNA and recognizes 7 classes of viruses
- 33. Clasisification on thebasis of host organism Plant VirusesAnimal Viruses Human Viruses
- 34.
- 35. How do virusesreplicate? Virus Replication Question ?
- 36. Viruses Replication General EARLYSTAGE CENTRAL STAGE FINAL STAGE
- 39. Viruses Replication Replication Earlystage of recognation, attachment, penetration and uncoating a. Recognation and attachment are due to interaction between each type of virus and specific receptor on the human cell. b. Penetration or entry is either by uptake into phagosome or by fusion of viral and host cell membranes c. Uncoating in the cell cytoplasm is by cell enzymes from lysosomes, which remove the virus protein coat and so make the viral genome accessible for the next stage
- 40.
- 41. Viruses Replication Replication Centralstage of mRNA synthesis, protein synthesis and genome replication 1. mRNA synthesis 2. Early protein synthesis 3. Genome replication 4. Late protein synthesis
- 42. Viruses Replication Replication a.mRNA synthesis by transcription The method of transcription to form depand on the genome, arranged by Baltimore classification (6 groups) Unnecessary for positive sense single strand RNA Viruses, where they definition their RNA is mRNA b. Early protein synthesis By translation of the above mRNA using host cell ribosomes in the citoplasm to make viral protein If the viral genome is a single nucleic acid molecule, one large polyprotein is produced and the claved by enzymes into a number of smaller proteins If the viral genome consist several mRNAs are made, each translated into one protein These early protein are usually enzymes and regulatory molecules for the next stage
- 43. Viruses Replication Replication c.Genome replication Like mRNA synthesis depend on type of genome d. Late protein synthesis Late protein synthesis of viral mRNA produces the capsid structural protein
- 44. Viruses Replication Replication Finalstage of assembly and release (with or without envelopment) Assembly of progeny virus particles Release of unenveloped virus Enveloped viruses
- 45. Viruses Replication Replication Finalstage of assembly and release (with or without envelopment) 1. Assembly of progeny virus particles Occurs in the cytoplasm Occurs in the nucleus (herpes, adeno, papilloma viruses) Occurs at the cell membrane of the host cell The viral genome is assembled with the capsid proteins and the viral enzymes into new viral progeny 2. Release of unenveloped virus Occurs in thought the host cell wall by rupture (“lysis”) Causing cell death
- 46. Viruses Replication Replication Finalstage of assembly and release (with or without envelopment) 3. Enveloped viruses Incorporating host cell nuclear or plasma membrane components Inserted viral proteins and glycoproteins to form the envelope prior to release Realese is usually by budding, and does not necessarily cause cell death Infectious enveloped virus can be shed for a long time
- 47.
- 48. Viral Genetic A. Mutations The RNA or DNA (“wild type”) of virus may mutate by 2 mechanisms: Mutations by base subtitutions One base of another by mistake or by mutagen (physical or c hemical). This mutations called a missense mutation if a different amino acids is code. This mutations called a nonsense mutation if no amino acids is code,stopping protein synthesis, and thus usually a lethal mutations Frameshift When one or more base pairs are deleted or added Thus shifting the reading frame and leading to the wrong amino acids Hence an inactive protein
- 49.
- 50. Viral Genetic B. Interaction(Genetic exchanges) Four major interaction can occur between host and virus, or 2 viruses infecting the same cell Recombination Reassortment Complementation Phenotypic mixing
- 52. Viruses and HumanDiseases
- 53. Viruses and HumanDiseases
- 54. Viruses and HumanDiseases
- 55.
Editor's Notes
- #3 Viruses were originally distinguished from other infectious agents because they are especially small (filterable) and because they are obligatory intracellular parasites. Virtually all cervical and anal cancers are caused by human papillomavirus (HPV). A vaccine against four HPVs is recommended for 11- to 12-year-old girls and boys. Epstein-Barr (EB) virus was isolated from Burkitt’s lymphoma Cells.
- #4 The question of whether viruses are living organisms has an ambiguous answer. Life can be defined as a complex set of processes resulting from the actions of proteins specified by nucleic acids. The nucleic acids of living cells are in action all the time. Because viruses are inert outside living host cells, in this sense they aren’t considered to be living organisms.
- #5 Viruses have few or no enzymes of their own for metabolism; for example, they lack enzymes for protein synthesis and ATP generation. To multiply, viruses must take over the metabolic machinery of the host cell.
- #8 Viral sizes are determined with the aid of electron microscopy. Different viruses vary considerably in size. Although most are quite a bit smaller than bacteria, some of the larger viruses (such as the vaccinia virus) are about the same size as some very small bacteria (such as the mycoplasmas, rickettsias, and chlamydias). Viruses range from 20 to 1000 nm in length.
- #9 The comparative sizes of several viruses and bacteria are shown in
- #12 A virion is a complete, fully developed, infectious viral particle composed of nucleic acid and surrounded by a protein coat outside a host cell. Viruses are classified by their nucleic acid and by differences in the structures of their coats
- #13 The nucleic acid of a virus is protected by a protein coat called the capsid . The structure of the capsid is ultimately determined by the viral nucleic acid and accounts for most of the mass of a virus, especially of small ones. Each capsid is composed of protein subunits called capsomeres.
- #19 In contrast to prokaryotic and eukaryotic cells, in which DNA is always the primary genetic material (and RNA plays an auxiliary role), a virus can have either DNA or RNA—but never both. The nucleic acid of a virus can be single-stranded or double-stranded. Thus, there are viruses with the familiar double-stranded DNA, with single-stranded DNA, with doublestranded RNA, and with single-stranded RNA. Depending on the virus, the nucleic acid can be linear or circular
- #29 Just as we need taxonomic categories of plants, animals, and bacteria, we need viral taxonomy to help us organize and understand newly discovered organisms. The oldest classification of viruses is based on symptomatology, such as for diseases that affect the respiratory system. This system was convenient but not scientifically acceptable because the same virus may cause more than one disease, depending on the tissue affected. In addition, this system artificially grouped viruses that don’t infect humans. viral species is a group of viruses sharing the same genetic information and ecological niche (host range). Specific epithets for viruses aren’t used. Thus, viral species are designated by descriptive common names, such as human immunodeficiency virus (HIV), with subspecies (if any) designated by a number (HIV-1)
- #32 Traditionally viruses have been classified phenotypically, by appearance, by size, by genome type, by replication strategy, by host, and by diseases caused. There are two main classification systems in use – the International Committee on Taxonomy of Viruses (ICTV) classification and the Baltimore classification system.
- #33 The Baltimore classification divides viruses into seven groups based on a combination of genome type and replication strategy, specifically how mRNA is formed from the original genome.
- #38 Following attachment, entry, and uncoating, the viral DNA is released into the nucleus of the host cell. Transcription of a portion of the viral DNA—the “early” genes—occurs next. Translation follows. The products of these genes are enzymes that are required for the multiplication of viral DNA. In most DNA viruses, early transcription is carried out with the host’s transcriptase (RNA polymerase); poxviruses, however, contain their own transcriptase. 3. Sometime after the initiation of DNA replication, transcription and translation of the remaining “late” viral genes occur. Late proteins include capsid and other structural proteins. 4. This leads to the synthesis of capsid proteins, which occurs in the cytoplasm of the host cell. 5. After the capsid proteins migrate into the nucleus of the host cell, maturation occurs; the viral DNA and capsid proteins assemble to form complete viruses. Complete viruses are then released from the host cell.
- #39 Pathways of multiplication used by various RNA-containing viruses. (a) After uncoating, single-stranded RNA (ssRNA) viruses with a + strand genome are able to synthesize proteins directly from their + strand. Using the + strand as a template, they transcribe − strands to produce additional + strands to serve as mRNA and be incorporated into capsid proteins as the viral genome. (b) The ssRNA viruses with a − strand genome must transcribe a + strand to serve as mRNA before they begin synthesizing proteins. The mRNA transcribes additional − strands for incorporation into capsid protein. Both ssRNA and (c) dsRNA viruses must use mRNA (+ strand) to code for proteins, including capsid proteins.
- #52 Model for antigenic shift in influenza virus. If a pig were infected with a human influenza virus and an avian influenza virus at the same time, the viruses could reassort and produce a new virus that had most of the genes from the human virus but a hemagglutinin and/ or neuraminidase from the avian virus. The resulting new virus might then be able to infect humans and spread from person to person, but it would have surface proteins (hemagglutinin and/or neuraminidase) not previously seen in influenza viruses that infect humans.