Topic 2 Virus structure and life cycle PDF

Foundations of Pharmacology PHRM2005 Dr. Ricky R Lareu Virus Structure and Life Cycle 2 Key Concepts Virus structure and life cycle Viral tropism Viral pathogenesis Types of viral infections Prions Learning Outcomes Understand that viruses are acellular and intracellular parasites Describe the major...

Foundations of Pharmacology PHRM2005 Dr. Ricky R Lareu Virus Structure and Life Cycle 2 Key Concepts Virus structure and life cycle Viral tropism Viral pathogenesis Types of viral infections Prions Learning Outcomes Understand that viruses are acellular and intracellular parasites Describe the major structural characteristics of viruses Outline the general life cycle of viruses Be able to compare-contrast the modes of cellular infection Be able to explain the major modes of transmission of viruses Define cell tropism Explain how viruses damage cells List and elaborate on the virus patterns of infection Be able to explain what prions are and outline the general method of propagation and cell damage 3 Lecture Information Reading and reference material: Mims’ Medical Microbiology 5th Ed., Chapter 3 Note on the recording there is a comment on slides 8 and 9 to ‘see diagram on slide 32’ but should be slide 10. This recording has been adapted from another lecture. 4 Characteristics of Viruses Viruses are not living organisms because they cannot carry out many life processes: are not made of cells - an isolated virus is merely a packaged set of genes in transit from one host cell to another cannot reproduce on their own - they are totally dependent on a host cell for replication - strict intracellular parasites do not grow or undergo division do not transform energy lack machinery for protein synthesis Living Multicellular Organism The vast majority of viruses contain only one type of nucleic acid: DNA or RNA, but not both. They must assemble into complete viruses (virions) to go from one host cell to another Non-living Acellular Infectious Agent 5 What are Viruses Made Of? Capsid – a protein coat which provides protection for viral nucleic acid and means for attachment to target host’s cells Made of protein subunits called capsomeres Some capsids are composed of a single type of capsomere; others composed of multiple types Capsid + nucleic acid is known as the nucleocapsid Genome – the virus genome is nucleic acid often packed around proteins: it can be double stranded DNA (dsDNA), single-stranded DNA (ssDNA), double stranded RNA (dsRNA) or single-stranded RNA (ssRNA) May be linear, several segments or singular and circular. It is much smaller than the genomes of cells. Genome type is used to classify viruses. Naked Virus Capsid Genome Capsomeres Enveloped virus 6 The Viral Envelope Animal viruses may have a membrane outer layer made up of lipids and proteins which surround the capsid. Acquired from host cell during viral release; the envelope is a portion of the membrane system of the host => it has a similar composition to the host’s cell membrane A virus which doesn't have an envelope is called a naked virus Helical Polyhedral Spherical Complex Spikes – virally-encoded proteins and glycoproteins Function in attachment of virion to host cell, and assist in entry into host cell 7 How Do Viruses Infect Cells and Reproduce? Four basic steps: Attachment, Entry, Replication, Release 1) Attachment – recognize and attach to host cell Most viruses infect only a certain type of host - called cell tropism. This specificity is due to the affinity of viral spikes (surface proteins) for host cell surface molecules ▪ Bacteriophages – proteins in their tail fibres, bind to bacterial surface molecules. ▪ Animal viruses have spikes that bind to specific glycoproteins on the surface of animal cells, present on capsid or envelope. 2) Entry – whole virus or genome enters target cell Direct penetration - Naked viruses spikes attaches to cell surface and inject their nucleic acid, capsid remains on cell’s surface. Endocytosis – Some naked and enveloped viruses can induce cell mechanism to take them – once inside the capsid is removed [see diagram on slide 10] Fusion – For some enveloped viruses, the envelope can fuse with the host cell membrane and release the capsid inside the cell – once inside the capsid is removed. [see diagram on slide 10] 8 How Do Viruses Infect Cells and Reproduce? 3) Replication – Virus takes over cell processes Host cell proteins read viral genetic instructions and manufacture viral components needed to build many new virus particles, including viral genome. See diagram on slide 10 These viral components self-assemble. 4) Release – new viruses exit the host cell Bacteriophage are released through cell lysis, with an enzyme called endolysin For animals viruses it depends if they are: ▪ Naked – After packaging and construction of capsid, viruses may be released from cell through exocytosis or may cause lysis and death of cell. ▪ Enveloped – Released through a process called budding o Virus exits cell with part of cell’s plasma membrane – envelope. 9 Diagrams for Virus Replication Processes Entry – Endocytosis Host plasma membrane Host plasma membrane Entry – Fusion Uncoating Uncoating Receptor sites Receptor sites Release - Budding © Gary E. Kaiser Release - Bacteriophage Image: Viral life cycle, National Academy of Sciences; Rubella virions budding, Copyright © motifolio.com 10 Cell Tropism of Viruses The affinity of a virus for specific body tissues (tropism) is determined by: Extracellular – The spikes on the virion bind to specific molecules on the target cell surface i.e. receptor-ligand or lock and key analogy. Intracellular: Some cells have specific transcription factors that recognize viral promoters and enhancer sequences on viral genome. The genes of a virus may be more efficiently expressed in the target cell type. Physical barriers – skin, mucous membranes Environmental can the virus survive e.g. local temperature, pH, and enzymes or other non-specific factors in body secretions In the gastrointestinal tract there are enzymes and bile that may inactivate some viruses 11 Viral Pathogenesis – How Do Viruses Cause Damage Pathogenesis - Process by which a parasites infection leads to tissue damage/disease Viral infection of a cell can result in: No apparent change, loss of cell function, cell death or transformation (cancer) Direct cell damage and death can be caused by: Direct lysis Competition by viral nucleic acids for proteins/enzymes involved in gene expression RNA polymerase and ribosomes Re-direction of the cell's energy and resources or shutdown of important pathways Indirect cell damage can result from: integration of the viral genome into the host DNA – mutation inflammation and the host immune response – often causing significant damage Image: Influenza virions electron micrograph, CDC, USA 12 Transmission of viruses Natural means: Horizontal transmission Direct person to person contact or aerosols e.g. Influenza, Measles, Faecal-oral route (polio) Mechanical – arthropod or animal bites e.g. yellow fever, dengue, rabies Vertical transmission Mother to offspring - HIV Unnatural means: Transfusion products, needle-stick injuries, sharing IV equipment Transplantation 13 Patterns of Viral Infection Sub-clinical Infection – Many viruses cause acute infections with symptoms in only a proportion of infected patients e.g. influenza, yellow fever, poliovirus (causes paralytic polio in