Viruses and Prions Lecture Notes

Chapter 5 Lecture Notes Viruses and Prions 1. Discovery of viruses: scientists discovered that a disease in tobacco plant was caused by a virus, an animal virus causes foot-and-mouth disease in cattle, and bodily fluids that were filtered to remove bacteria remained infectious indicating there were infectious agents smaller than bacteria 2. Role of viruses in evolution: infect cells and influence their genetic makeup, 8% of the human and 10-20% of bacterial genome contains viral sequences 3. Properties of viruses a. Obligate intracellular parasites: cannot multiply unless they invade a host cell and instruct its machinery to make and release new viruses since they lack enzymes for most metabolic processes and machinery for protein synthesis b. Infect: bacteria, algae, fungi, protozoa, plants, and animals, ubiquitous in nature and have had a major impact on development of biological life c. Classification and naming: based on hosts and diseases they cause, their structure and chemical composition, and similarities in genetic makeup, the Internal Committee of the Taxonomy of Viruses classifies and categorizes viruses d. Size: 20nm to 1,000nm diameter, almost all require an electron microscope to visualize e. Describing viruses: active/inactive instead of alive/dead since they are non-living and unable to multiply independent from a host f. Attachment to host cells: molecules on virus surfaces provides high specificity for host cell attachment g. Viral structure: capsid, nucleic acids, may have one or two enzymes, may have an envelope, not a cell and do not independently fulfill the characteristics of life i. Capsid: protein shell that surrounds nucleic acid 1. Nucleocapsid: capsid together with nucleic acids 2. Capsomeres: identical protein subunits that spontaneously self-assemble into the finished capsid 3. Three types: helical (hollow cylinders), icosahedral (3D, vary in number of capsomeres), and complex (never enveloped) ii. Envelope: covering external to the capsid that is usually a modified piece of the host's cell membrane from budding 1. Naked viruses consist only of a nucleocapsid 2. Enveloped viruses can bud from the cell membrane, nuclear envelope, or the endoplasmic reticulum, and are pleomorphic due to the flexibility the envelope confers iii. Spikes: project from the nucleocapsid or the envelope and allow viruses to dock onto host cells iv. Virion: fully formed virus that is able to establish an infection in a host cell v. Nucleic acids: DNA or RNA, not both 1. Only possess genes needed to invade host cells and redirect their activity 2. DNA: double- or single-stranded 3. RNA: double- or more often single-stranded a. Positive-sense RNA: ready for immediate translation b. Negative-sense RNA: used as a template to make mRNA before translation c. Segmented: individual genes exist on separate pieces of RNA d. Retroviruses: possess enzymes to create DNA from their RNA 4. Baltimore Classification System: describes how each type of virus makes mRNA TYPES OF VIRAL GENOMES Class I dsDNA Class II ssDNA Class III dsRNA Class IV (+) ssRNA Class V (-) ssRNA Class VI ssRNART Class VII dsDNA-RT STRATEGY EXAMPLE dsDNA → mRNA Herpes simplex (herpes) ssDNA → dsDNA → mRNA Parvovirus B19 (skin rash) dsRNA → mRNA Rotavirus (gastroenteritis) (+) ssRNA → (-) ssRNA → mRNA Poliovirus (polio) (-) ssRNA → mRNA ssRNA-RT → DNA/RNA → dsDNA → mRNA dsDNA-RT → mRNA Influenza virus (influenza) HIV (AIDS) Hepatitis B virus (Hepatitis B) vi. Other components 1. Enzymes a. Polymerases: synthesize DNA and RNA b. Replicases: copy RNA c. Reverse transcriptase: synthesizes DNA from RNA d. Most viruses lack the genes for synthesis of metabolic enzymes 2. Taking components from host cell a. Arenaviruses: take host ribosomes b. Retroviruses: use host tRNA molecules h. Multiplication cycles of animal viruses: dictate the way the virus is transmitted, what it does to the host, immune responses, human measures to control viral infections, vary in length i. Adsorption 1. Virus encounters susceptible host cell and adsorbs specifically to receptors on the cell membrane that are usually proteins the cell requires for normal function 2. Glycoprotein spikes on the envelope or on the capsid of a naked virus binds to the receptors on the membrane 3. Host range: range of cells that a virus can infect a. b. c. d. Restricted: Hepatitis B, only infects liver cells of humans Moderate: Poliovirus, infects intestinal and nerve cells of primates Broad: rabies, infects various cells of mammals Cells that lack compatible virus receptors are resistant to adsorption and invasion by that virus e. Tropisms: specificities of viruses for certain tissues ii. Penetration and uncoating 1. Virus or its nucleic acid penetrates the host cell membrane a. Endocytosis: entire virus is engulfed by the cell and enclosed in a vacuole or vesicle, enzymes in the vacuole may break down the capsid, freeing the nucleic acid b. Fusion: viral envelope fuses with cell membrane, nucleocapsid enters cell, nucleic acids uncoated iii. Synthesis 1. Replication and protein production a. DNA viruses: enter nucleus for replication and assembly b. RNA viruses: enter cytoplasm for replication and assembly c. Retroviruses: copies its RNA into DNA, complex life cycle 2. Example 1: +ssRNA viruses a. +ssRNA serves as mRNA and is translated into viral proteins, especially those useful for further viral replication b. +ssRNA is replicated into -ssRNA, becoming the template for the creation of many new +ssRNAs that are used as the viral genomes of new viruses, additional +ssRNAs are synthesized and used for late-stage mRNAs c. Some viruses are equipped with the necessary enzymes for synthesis of viral components, others utilize those of the host d. Proteins for the capsid, spikes, and viral enzymes are synthesized on the host's ribosomes using its amino acids 3. Example 2: DNA viruses a. Early phase i. Viral DNA enters nucleus and genes are transcribed into mRNA ii. mRNA moves into cytoplasm to be translated into viral protein/enzymes needed to replicate the viral DNA iii. Host cell's DNA polymerase is involved b. Late phase i. Parts of viral genome are transcribed and translated into proteins required to form the capsid and other structures ii. New viral genomes and capsids are assembled iii. Mature viruses are released by budding or cell disintegration iv. Assembly 1. Mature viruses are constructed from the growing pool of parts 2. Capsid is first laid down as an empty shell that will serve as the receptable for the nucleic acid 3. Viral spikes are inserted into the host's cell membrane so they can be picked up as the virus buds off with its envelope v. Release 1. Nonenveloped and complex viruses: reach maturation in nucleus or cytoplasm and are released when the cell lyses or ruptures 2. Enveloped viruses: liberated by budding from the membranes of the cytoplasm, nucleus, endoplasmic reticulum, or vesicles a. Nucleocapsid binds to the membrane, which will curve completely around it and form a small pouch b. The pouch will pinch off and release the virus with its envelope 3. The number of viruses released by infected cells varies and is controlled by: the size of the virus and the health of the host cell a. Poxvirus-infected cell: may release 3,000-4,000 virions b. Poliovirus-infected cell: may release up to 100,000 virions c. With large numbers of virions released by some infected cells, there is potential for rapid viral proliferation as the released viruses encounter susceptible cells