Chapter 13: Viruses and Prions - Fall 2022 PDF

Chapter 13: Viruses and Prions Human Immunodeficiency Virus (HIV) (Depicted in green, budding off infected white blood cell.) Viruses were not finally discovered until 1935 with the invention of the el...

Chapter 13: Viruses and Prions Human Immunodeficiency Virus (HIV) (Depicted in green, budding off infected white blood cell.) Viruses were not finally discovered until 1935 with the invention of the electron microscope Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Discovery of Viruses: 1886: Adolf Meyer showed that TMD was transmissible from an infected plant to a healthy plant 1892: Dimitri Iwanowski found that the cause of TMD was filterable. 1930: the word “virus” meaning “poison” was used to describe filterable agents of disease 1935: Wendell Stanley isolated the virus responsible for TMD, invention of electron microscope Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Living or Non-living? ✔What is life? - complex process resulting from actions of proteins encoded for by nucleic acids that carry out essential biological processes Viruses are not living organisms because they are incapable of carrying out all life processes. Viruses: –are not made of cells –cannot reproduce on their own –do not grow or undergo division –do not transform energy –lack machinery for protein synthesis Nonliving / Acellular Infectious Agent: H1N1 Influenza Virus Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Definition of a Virus: ✔Contain single type of nucleic acid: DNA or RNA, never both ✔Protein coat surrounds the nucleic acids ✔Multiply inside a living cell by using the cell’s metabolic machinery ✔ Cause virions (specialized structures used to transfer viral nucleic acids) to be made by the host cell Additionally: -very small, filterable -obligate intracellular parasites -BUT: these characteristics shared by some bacteria also Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Viral sizes and shapes: Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings  Virus Structure Capsid Covering Envelope (not Virus found in all viruses) Particle Nucleic acid molecule (virion) Central core (DNA or RNA) Matrix proteins enzymes (not found in Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings all viruses)  Viral Structure: Capsid ✔ Capsid: protein coat surrounding viral nucleic acids ✔Structure of capsid: - determined by viral nucleic acids - composed of subunits:capsomeres Functions: ✔Protection of viral nucleic acids ✔Important for attachment to host cells ✔Useful in identifying viruses ✔Determines theInc., Copyright © 2006 Pearson Education, shape publishing of the Cummings as Benjamin virus Viral Structure: Envelopes ✔In some viruses: - capsid enclosed by an envelope ✔Envelope structure: - lipids, proteins and carbohydrates - sometimes made up of host cell plasma membrane - sometimes covered in spikes ✔Spikes: - carbohydrate-protein complexes - project from envelope surface Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Advantages/Disadvantages of Envelopes: ✔Advantages: 1. Envelopes acquired from host cell plasma membrane - allows virus to escape/evade host immune system 2. Because so similar to host cells: - also helps an enveloped virus fuse with a host cell to help it invade ✔Disadvantages: 3. Envelopes are damaged easily - narrow pH range, narrow temperature range - susceptible to lipid solvents - Enveloped virus are more sensitive to antimicrobial agents than naked viruses Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Functions of viral surface coat: ✔Attachment to host cells - non-enveloped viruses: capsid - enveloped: envelope or spikes ✔ Protection of viral nucleic acids ✔ Immune evasion: mutations - viral nucleic acids encode for surface coat - these genes susceptible to mutation - changes the structure of the surface coat Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Viral Morphology: ✔Viruses can be classified based on the architecture (shape, structure) of the capsid 1. Helical viruses 2. Polyhedral viruses 3. Complex viruses Naked & Enveloped viruses Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings  Helical Viruses: 1. Non-enveloped (naked) helical virus: TMV 2. Enveloped helical viruses: Influenza Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings  Polyhedral Viruses: Adenovirus ✔Polyhedral: “many sided” - most viruses are icosahedron- 20 triangular faces, 12 corners famous “naked” virus ~ poliovirus Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Complex Viruses: Bacteriophages A. Bacteriophages: - capsids have additional structures attached (sheath, base plate, pins, tail fibers) Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Complex Viruses: Poxviruses B. Poxviruses: - no clear capsid - multiple membranes surrounding nucleic acids Examples: 1. Vaccinia virus (smallpox) Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Viral Host Range: Host range: spectrum of host cells a virus is capable of infecting ✔ Virus specificity: - viruses can infect specific cells within a single host species - specificity determined by: - receptor sites on host surface for viral attachment Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Viral Taxonomy: ✔Viruses grouped into families based on: 1. Nucleic acid type 2. Strategy of replication 3. Morphology ✔Family names have the suffix: “-viridae” Ex: Retroviridae ✔Genus names have the suffix: “-virus” Ex: Lentivirus ✔Viral species: group of viruses that share the same: 4. Genetic information 5. Ecological niche (host) - no specific epithet - designated by descriptive common name: Human immunodeficiency virus (HIV) - subspecies designated by numbers (HIV- 1) publishing as Benjamin Cummings Copyright © 2006 Pearson Education, Inc., Nucleic Acid Classification of viruses: 1st: Is their genome made up of RNA or DNA? 2nd: For RNA viruses: is their RNA double-stranded (dsRNA) or single-stranded (ssRNA)? - most RNA viruses have ssRNA 3rd: For single-stranded RNA genomes: is the RNA a positive (+) sense strand or a negative (-) sense strand? - positive (+) sense strand: RNA acts like mRNA - can be translated into protein by host ribosomes - negative (-) sense strand: acts as a template for (+) RNA - first transcribed to make complimentary (+) RNA - then (+) RNA is translated by host ribosomes Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Viral Mechanisms of Multiplication: A. Bacteriophages: 1. Lysogenic Cycle: the silent virus infection 2. Lytic Cycle: the death cycle B. Animal Viruses: 1. DNA viruses 2. RNA viruses a. Single-stranded, + strand RNA viruses b. Single-stranded, - strand RNA viruses c. Double-stranded RNA viruses d. Retroviruses Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Bacteriophages Phages are Viruses That Infect Bacteria Viral Replication: Bacteriophages ✔Two mechanisms of replication of bacteriophages: 1. Lytic cycle: death of host cell Example: T-even bacteriophages 2. Lysogenic cycle: host remains alive - viral DNA incorporated into host DNA Example: Lambda bacteriophage Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings  How Do Phages Reproduce? A bacteriophage is a virus that attacks and destroys bacterial cells. Bacteriophage replication: LYTIC CYCLE 1. Adsorption: Phage attaches by tail fibers to host cell 2. Penetration: Phage lysozyme opens cell wall, tail sheath contracts to force tail core and DNA into cell 3. Biosynthesis: Production of DNA and proteins 4. Maturation: Assembly of phage particles 5. Release: Phage lysozyme breaks cell wall Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Lytic cycle: Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Lytic cycle: Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings  Phage Growth Cycle: Penetration thru phage release Penetration thru biosynthesis Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings The Lysogenic Cycle: Bacteriophage C Viral Mechanisms of Multiplication: A. Bacteriophages: 1. Lysogenic Cycle: the silent virus infection 2. Lytic Cycle: the death cycle B. Animal Viruses: 1. DNA viruses 2. RNA viruses a. Single-stranded, + strand RNA viruses b. Single-stranded, - strand RNA viruses c. Double-stranded RNA viruses d. Retroviruses Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Multiplication of Animal viruses:  1. Adsorption: Viruses attach to cell membrane  2. Penetration* by endocytosis or fusion  3. Uncoating * * by viral or host enzymes  4. Biosynthesis * : Production of nucleic acid and proteins  5. Maturation *: Nucleic acid and capsid proteins assemble  6. Release* by budding (enveloped viruses) or rupture *Different mechanistically from bacteriophages ** Unique to animal viruses Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Animal viruses: Attachment to host cells ✔Viruses have attachment sites that bind to host cell receptor sites - host receptor sites: proteins and glycoproteins on host cell plasma membrane - inherited characteristic of host cells - can vary from person to person - contributes to susceptibility to certain viruses - antibodies against viral attachment sites can be used to treat some viral infections Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings  Animal viruses: Penetration Endocytosis: Fusion: Enveloped viruses ONLY! Animal Viruses: Uncoating ✔Unique to Animal Viruses ✔Uncoating: separation of viral nucleic acids from protein coat - occurs once inside vesicle or host cell cytoplasm - Mechanism varies among viruses: 1. Lysosomal enzymes present in vesicles of host cell - digests capsid protein 2. Specific enzyme encoded by viral nucleic acids that is synthesized after penetration (poxviruses) 3. Enzymes found within host cell cytoplasm 4. Poliovirus: uncoating occurs while attached to host cell plasma membrane Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Animal Viruses: Biosynthesis ✔ Mechanisms of Biosynthesis differ based on type of nucleic acid the virus has 1. DNA viruses 2. RNA viruses a. Single-stranded, + strand RNA viruses b. Single-stranded, - strand RNA viruses c. Double-stranded RNA viruses d. Retroviruses Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Biosynthesis/Multiplication of DNA viruses: ✔General information: - DNA replicated in nucleus of host cell using host or sometimes viral enzymes - capsid proteins made in cytoplasm using host enzymes - capsids migrate to nucleus for assembly into virions ✔One exception to above generalizations: Poxviruses - all components synthesized and assembled in host cell cytoplasm Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Multiplication of DNA Virus: Copyright © Biosynthesis/Multiplication of RNA viruses: ✔RNA viruses multiply entirely in the cytoplasm of the host cell ✔Several different mechanisms of mRNA formation 1. ssRNA (+) strand (sense strand) 2. ssRNA (-) strand (antisense strand) 3. dsRNA: have both (+) and (-) strands 4. Retroviruses ✔(+) strand (sense) RNA: can be directly translated into viral proteins - essentially viral mRNA ✔(-) strand (antisense) RNA: is complementary to viral mRNA -must be copied into (+) strand RNA prior to translation -requires a virus- specific RNA dependent RNA-polymerase - generally packaged into virion Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Release of an Enveloped Virus by Budding: Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 13.20  The Reproductive Cycle of a Retrovirus 1. 2. 3. 4. 5. Building Reverse Integration Transcription Assembly and transcription and and entry Translation Release Viral DNA Cell DNA Viral RNA and proteins Receptor A retrovirus is an enveloped ssRNA virus. It relies on the enzyme reverse transcriptase to use its RNA genome to build DNA, which can then be integrated into the host's genome. The virus then replicates as part of the cell's DNA. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings  The Reproductive Cycle of a Retrovirus A retrovirus is an enveloped ssRNA virus. It relies on the enzyme reverse transcriptase to use its RNA genome to build DNA, which can then be integrated into the host's genome. The virus then replicates as part of the cell's DNA. How does HIV enter T-cells and Macrophages? Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings The fate of the host cell Budding of a HIV virion Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Course of HIV infection Less than 200 T Helper cells is indicative of AIDS Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Opportunistic Infections of AIDS patients  Protozoan  Toxoplasmosis  Fungal Pneumocystis carinii, candidiasis, cryptococcosis, histoplasmosis  Bacterial Mycobacterium avium complex, atypical mycobacterial disease, Salmonella septicaemia, multiple or recurrent pyogenic bacterial infection  Viral  CMV, HSV, etc. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings  Hidden Viruses When bacteriophage DNA becomes integrated into DNA of host bacteria it is called a prophage. When an animal virus becomes integrated in host cells, it is called a provirus. The provirus condition is permanent; it becomes a permanent physical part of host’s chromosome (examples: HIV, Varicella zoster (chicken pox), herpes Varicella zoster, and other Herpes Image: Bacteriophage Lysogenic Replication, Suly12 Wikimedia viruses can become proviruses, Commons; Varicella zoster Herpesvirus, PHIL 1878. because have DNA as genetic material Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings  Persistent Latent (dormant) Infections Herpes Simplex virus (Herpes virus) - hides in dorsal root ganglia EBV Epstein Bar Virus (Herpes virus) - hides in B lymphocytes Varicella-Zoster (Herpes virus) - hides in sensory ganglia Hepatitis B (Hepadnavirus) - hides HIV (Lentivirus) in liver cells These infections avoid - hides in T cells the immune system;they Cytomegalovirus (Herpes virus) do not enter the lytic - hides in many cells cycle, Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings the cell is not What reactivates latent infections? Event Virus -Age -Varicella-Zoster -Pregnancy -CMV, Herpes 2 -Immunosuppression -Herpes, CMV, EBV, Hep. B, Varicella-Zoster Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Persistent Chronic Infections  Infectious virus is produced and can be recovered over long periods of time -Hepatitis B and C; chronic liver disease and liver cancer. -Human papilloma virus (HPV) causes warts and cervical cancers. - Human T cell leukemia virus (HTLV) Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings  Viruses and Cancer: ✔Cancer: uncontrolled, invasive growth of abnormal cells - can result in a neoplasm: localized accumulation of cells (often referred to as a tumor) - malignant tumors: invade neighboring tissues and interfere with the normal functioning of these tissues - if these tumors spread to other parts of the body they are said to have metastasized ✔1911: the discovery that some viruses cause cancer Examples: 1. Epstein-Barr Virus (EBV) is associated with Burkitt’s lymphoma- malignant tumor- causes destruction of jaw 2. Human Papillomaviruses (HPV) is associated with several types of cancers including cervical and oral cancer. Viruses and Cancer: ✔ Anything that causes alterations in genetic material (DNA) has the potential to cause cancer ✔Not all cancers are caused by viruses AND not all viruses can cause cancer ✔The ability of a virus to cause cancer depends on: - ability of virus to integrate viral DNA into host cell chromosomes (form provirus) - primarily DNA viruses - only RNA viruses that are oncogenic are Retroviruses Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings How viruses cause cancer: Copyright © 2006 Pearson Education, Influenz a The symptoms start abruptly FEVER, chills HA and NA of Influenza A viruses change their anti HEADACHE determinants more rapid than those of B and C ch MYALGIA, ARTHRALGIA Dry COUGH RHINITIS, SORE THROAT OCULAR SYMPTOMS Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Influenza virus  Hemagglutinin  H spikes used for attachment to host cells (15 subtypes)  Neuraminidase  N spikes used to release virus from the cell (9 subtypes)  Viral strains identified by variation in the H and N spikes  (ex. H5N1) Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Antigenic Shift Changes in H and N spikes due to genetic recombination between different strains infecting the same cell Mechanism of immune evasion may produce pandemics Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings  Mixing in the pig  Pigs are thought to serve as a “mixing vessel,” allowing for genetic exchange between avian and human viruses when the same cell is infected with both virus types.  Most of these hybrid viruses are not infectious and represent an evolutionary dead end.  However, if the mixing in the pig results in a successfully infectious virus to humans, there is a chance that the neutralizing antibodies from previous influenza infections will not recognize the novel subtype, and a pandemic might occur.  This chance for this scenario to take place is great where large number of pigs, ducks and humans are in close contact. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings  Influenza Virus  In general: - H1, H2 and H3 strains are known to infect humans - H4, H5, H6 and H7 strains primarily infect animals - mostly swine and poultry - however, recombination of strains have lead to H5N1 and H7N7 infecting and causing disease in humans Viral neuraminidases: - N1 and N2 = linked to human epidemics - N3 and N7 = linked to a number of isolated deaths, but not epidemics or pandemics Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings  Influenza An influenza pandemic is an epidemic of an influenza virus that spreads on a worldwide scale infecting many people. In contrast to regular seasonal epidemics of influenza, pandemics occur irregularly, with the 1918 Spanish flu the most serious pandemic in recent history. Pandemics can cause high levels of mortality, with the Spanish influenza having been Avian influenza A H5N1 viruses (seen in gold) do not usually infect humans; however, several instances of human responsible for the deaths of 50 – 100 million infections and outbreaks have been reported since 1997 people worldwide. (Source CDC PHIL #1841). ~ 3 influenza pandemics in each century for the last 300 years. Occur when a new strain of influenza virus is Seasonal Flu Bird Flu transmitted to humans from animals (especially pigs, chickens and ducks). These new strains are unaffected by immunity people may have to older human flu strains, so can spread rapidly. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings For more info see: http://www.pandemicflu.gov Flu Outbreaks Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings The 1918 Influenza Epidemic: H1N1 Swine Flu  The deadliest strain of influenza identified to date - 20 million people died worldwide (1 in 30) - mostly young adults - death occurred rapidly, within a few hours of symptom onset Why so deadly? - 10 amino acids changed - created gene that allowed virus to attach to, invade and multiply in lung cells - cytokine storm Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings 1918 Influenza: Cytokine Storm Influenza is caused by an enveloped ssRNA virus. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings How Can Viral Diseases Be Prevented and Treated?  Good hygiene  Avoid contact with contaminated food, water, fecal material or body fluids.  Wash hands frequently.  Vaccines  Stimulate natural defenses with in the body.  Contain a component of or a weakened or ‘killed” virus particles.  Not available for all viruses.  Anti-viral drugs (but not antibiotics)  Available for only a few viruses.  Inhibit some virus development and/or relieve symptoms. Two Types of Influenza vaccines: ✔Flu shot: - inactivated whole-agent vaccine (killed virus) - safe for ages older than 6 months - safe for pregnant women and people with underlying medical conditions ✔Nasal Spray flu vaccine: - living, attenuated whole- agent vaccine (live virus) - safe for healthy people aged 2- 49 - not safe for: - pregnant women - people with underlying medical conditions Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings The Seasonal Influenza Vaccine: ✔Multivalent vaccine: - directed at the three most important strains identified each year (generally 2 type-A strains, 1 type-B strain) - strains collected at 100 centers worldwide and analyzed - vaccine strains have to be identified by February - only 70-90% effective ✔Problems with vaccine development: - vaccine viruses grown in chick embryos (time intensive!) - doesn’t allow for response to new viral strains - it’s essentially an educated guessing game each year - viral strains differ every year Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Diagnosis and Treatment of Influenza: ✔Diagnosis: - can’t diagnose solely on clinical symptoms - rapid identification tests available for Type-A and Type-B influenza viruses ~70% sensitive ✔Treatment: - antiviral drugs: rimantadine and amantadine - reduce clinical symptoms of Influenza A if administered early - inhibitors of Neuraminidase: 1. Zanamivir (Relenza) 2. Oseltamivir phosphate (Tamiflu) - both shorten duration of symptoms if taken within 30 hours of symptom onset Virus-like agents: Prions PrP: prion protein - exist normally in plasma membranes of mammalian cells - mostly found in brain cells When PrP becomes a problem: - when they become folded incorrectly - prevents proper organization in cell membranes - leads to cell death Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings  Prions Prions are infectious agents even simpler than viruses. Responsible for fatal neurodegenerative diseases called transmissible spongiform encephalopathies (TSEs). Can enter brain usually after being ingested, or arise from a mutation. In brain, causes normal proteins to refold into abnormal shape. As prion proteins multiply, neurons are destroyed and brain tissue becomes riddled with holes. Unlike all other known agents of infection, they appear to lack nucleic acid (DNA or RNA). TSEs include: - Creutzfeldt-Jakob (kroits-felt yock-ub) disease - mad cow disease - scrapies (neuro disease of sheep & goats) Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Properties of Prions: 1. Resistant to high heat (above 90C) - would normally inactivate a virus 2. Resistant to radiation - would normally inactivate viral nucleic acids 3. Resistant to enzymes that damage nucleic acids 4. Sensitive to agents that denature proteins Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Prion Diseases: spongiform encephalopathies Normal Brain: Prion-infected brain: General symptoms: Diseases: 1. Neural degeneration 1. CJD: Creutzfeld-Jacobs Disease 2. Loss of motor function 2. BSE: bovine spongiform 3. Eventual death encephalopathy (Mad Cow) 3. Scrapies Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Transmission of Prion Diseases: