Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
10/30/2016 Viruses, viroids, and prions Chapter 13 BIO 220 Fig. 13.1 Characteristics of viruses • Very, very small (filterable) • Obligatory intracellular parasite • They have no ribosomes, so must use host cell machinery to translate viral mRNA into viral proteins • Do not store or generate ATP, so energy is derived from the host cell • Parasitize host cell for building materials like amino acids, lipids, and nucleotides • Without the host cell, viruses can not carry out “life”-sustaining processes 1 10/30/2016 Host range of virus • Spectrum of cells virus can invade • Most viruses can only infect specific types of cells of only one host species • Range determined by – Virus must be able to interact with specific receptor sites on host cell surface – Availability within the specific host of cellular factors necessary for viral multiplication Viral structure • Viruses are composed of a nucleic acid surrounded by a protein coat called a capsid • Some viruses have a lipid/protein/CHO envelope surrounding the capsid • A virion is a complete, fully developed, infectious viral particle located outside a host cell Nucleic acids • Virus can have DNA or RNA • Nucleic acid can be ds or ss • Nucleic acid may be a few thousand nucleotides up to 250,000 nucleotides • Nucleic acid may be circular or linear • For some viruses, the percentage of nucleic acid in relation to protein is about 1% (influenza), can be up to 50% (certain bacteriophages) 2 10/30/2016 Capsid • This is the protein coat covering the viral nucleic acid • Protein subunits of capsid are called capsomeres • Functions: – Protection – Contains attachment sites – Proteins allow viral penetration of host cell Fig. 13.2 3 10/30/2016 Envelopes • Nonenveloped viruses lack an envelope • Enveloped viruses do have an envelope • Some viral capsids are covered by envelopes which may be made of lipids, proteins, and CHOs Spikes • May be means of attachment to host cells • May be used as a means of identification – May be a result of extrusion from host cell – Viral nucleic acid codes for envelope proteins, other components derived from the host cell • Some envelopes may be covered in spikes (CHO/protein complexes) Fig. 13.3 Influenza • HA spikes (hemagglutinin spikes) – Binds sialic acid on host cell membranes – Bind to erythrocytes and form cross bridges, resulting in agglutination – Targeted by antibodies against the influenza virus • NA spikes (neuraminidase spikes) – Enable virus to be released from host cell – Required for viral replication – Target of drugs like Tamiflu • Spikes can be used for identification of subtypes Influenza classification • A – infects humans and several types of animals (i.e. birds, horses, swine) • B – humans • C – humans, swine, dogs • Influenza pandemics are caused by Type A viruses, which are classified into subtypes based on the HA and NA spikes • HA (17 versions), NA (10 versions) 4 10/30/2016 Viruses are tricky • Some viruses have evolved mechanisms for evading antibodies (that were produced in response to that particular virus) – Viral genes, including those determining viral surface proteins, are susceptible to mutation – The progeny of mutant viruses therefore have altered surface proteins (slight changes in spikes), which are not recognized by the antibodies – Antigenic drift Viral morphology Antigenic shift • A major change in the virus that results in new combinations of HA and NA proteins • Can take place when a human or animal is infected with two different subtypes of virus • Reassortment of nucleic acids can result in a modified virus that humans do not have immunity to Based on capsid architecture • • • • Helical (rabies, Ebola) Polyhedral (adenovirus, poliovirus) Enveloped (influenza) Complex Fig. 13.4a – Bacteriophages Fig. 13.5a 5 10/30/2016 Classification of viruses • • • • • • Way people imagined they were contracted Scientists that discovered them Based on disease they produce Animal/tissue affinity Host range or specificity Morphological characteristics – Type of nucleic acid/enveloped or naked/capsid size/capsid architecture Plaque method How can we grow viruses in the lab to study them? For animal viruses . . . • Grow virus in live animals • Chicken embryos • Cell/tissue culture Bacteriophages • Much easier to grow in lab Viral multiplication • The virion nucleic acid contains only a few genes for viral replication – Genes for viral structural components – Genes for enzymes used in viral life cycle (i.e. replicating viral nucleic acid) – Some virions contain a few preformed enzymes – Genes are only transcribed and proteins made if virus is in host cell • Most everything else is supplied by host cell Fig. 13.6 Plaque forming units – each plaque corresponds to a single virus 6 10/30/2016 Viral one-step growth curve Bacteriophage multiplication • The lytic cycle (T-even bacteriophage) – Ends with the lysis and death of host cell • The lysogenic cycle (Bacteriophage λ) – Host cell lives Fig. 13.10 Virulent phages • Undergoes the lytic cycle Phage lysozyme • The result of the lytic cycle is viral replication and death of the host cell as mature virions are released Degradation host DNA Viral mRNA transcribed/translated Phage components synthesized Lysozyme Fig. 13.11 7 10/30/2016 Induction Temperate phages • Can undergo a lytic or lysogenic cycle, depending on environmental conditions • In the lysogenic cycle the phage DNA is incorporated into the bacterial chromosome Prophage gene repression – Prophage is inactive during this period Fig. 13.12 • The phage DNA can be excised via induction and then enter the lytic cycle Some phages (temperate phages) may proceed through a lytic cycle, but also have the ability to incorporate their DNA into the host cell’s DNA to begin a lysogenic cycle. Consequences of lysogeny • Lysogenic cells are immune to reinfection by the same phage • Phage conversion – host cell may exhibit new properties, i.e. toxin production – Corynebacterium diphtheriae, Clostridium botulinum • Specialized transduction is possible – When a prophage is excised from its host chromosome, it can take with it a bit of the adjacent DNA from the bacterial chromosome Fig. 13.13 8 10/30/2016 Multiplication of animal viruses • • • • • Attachment Entry Uncoating Biosynthesis of virus Maturation and release The type of nucleic acid as well as whether or not the virus has an envelope will determine the life cycle of an animal virus. Multiplication of animal viruses • Attachment – Animal viruses have attachment sites that bind to receptor sites on host cell PM • Entry – Many viruses enter by receptor-mediated endocytosis – Fusion (enveloped viruses) Multiplication of animal viruses • Uncoating – This is the step where the capsid is removed from the viral nucleic acid • Host lysosomal enzymes • Enzymes encoded by viral DNA that are synthesized soon after infection Fig. 13.14 9 10/30/2016 Biosynthesis of DNA viruses • Generally, DNA viruses replicate their DNA in the host cell nucleus by using viral enzymes • Capsid synthesis in cytoplasm • Virion assembly in nucleus • Virions transported to PM for release Papovavirus – naked, dsDNA Fig. 13.15 DNA viruses • Papovaviridae (naked) Biosynthesis of RNA viruses • Virus multiplies in cytoplasm – Human papilloma virus • Herpesviridae (enveloped) • Adenoviridae (naked) • Hepadnaviridae (enveloped) • Viral RNA codes for RNA-dependent RNA polymerase, which makes a complementary copy of RNA – Hepatitis B • Poxviridae (enveloped) 10 10/30/2016 Zika virus • ss +RNA virus, enveloped • Member of flaviviridae • Transmitted by Aedes mosquitos, but sexual transmission is also possible • Zika fever symptoms include headache, fever, maculopapular rash, and conjunctivitis, but symptoms vary Synthesis of host RNA inhibited Fig. 13.17 – Can cause a birth defect called microcephaly – Can also cause Guillain-Barre syndrome in adults +RNA virus (ss) Picornaviridae (poliovirus, enterovirus) Detection and treatment Detection • PCR (detection of viral RNA) • Presence of antibodies in serum Treatment • None • Vector control! – Wolbachia -RNA virus (ss) Fig. 13.17 11 10/30/2016 Biosynthesis of RNA viruses that use DNA Original viral RNA degraded Virus may remain in a latent state or may be expressed Retroviruses & oncogenic RNA viruses Fig. 13.19 Fig. 13.17 HIV HIV infection of target T cells A retrovirus (Lentivirus) Two strands of RNA Reverse transcriptase Phospholipid envelope with gp120 spikes • Spread by dendritic cells • Activated CD4+ cells are main target • • • • Fig. 19.13 Fig. 19.13 12 10/30/2016 Infection in CD4+ cells Fig. 19.14 Infection in APCs Fig. 19.15 HIV subtypes How is HIV able to persist? • Integrated in host genome as provirus • Virus may not be released by infected cells (stored as latent virions in vacuoles) • Some infected cells become a reservoir for the virus • Cell-cell fusion • Rapid antigenic changes due to reverse transcriptase activity (high mutation rate) • HIV-1 – Most virulent – Accounts for 99% of cases – Related to viruses in western Africa that affect primates – Further subdivided by letter . . . • HIV-2 – Related to virus that affects the sooty mangabeys – Not common outside of Africa – Patients may be asymptomatic for lengthy periods 13 10/30/2016 Acquired Immunodeficiency Syndrome (AIDS) • Final stage of human immunodeficiency virus (HIV) infection • Patients susceptible to infections due to suppressed immune activity Fig. 19.16 HIV detection • ELISA (detection of HIV antibodies) • Western blots • Real-time PCR 14 10/30/2016 HIV transmission • • • • • • • • • Drugs that inhibit the HIV life cycle Blood Semen Intimate sexual contact Breast milk Transplacental Blood-contaminated needles Organ transplants Artificial insemination Blood transfusion Fig. 19.18 Maturation and release • • • • Budding Capsid is assembled Nucleocapsid forms Naked viruses cause rupture of the host cell Enveloped viruses often leave the host cell via a process called budding – Envelope proteins are encoded by viral genes and are inserted in host cell PM – Envelope forms as virion leaves the host Fig. 13.20 15 10/30/2016 Transformation of normal cells into cancer cells • Can be due to viruses • Cancer-inducing genes (oncogenes) carried by viruses are actually derived from animal cells • Oncogenes can be activated to abnormal functioning by a variety of factors • Oncogenic viruses can induce tumor formation – Virus integrates into host cell DNA and replicates along with the host cell DNA, ultimately transforming host cell • After being transformed by viruses, tumor cells contain a virus-specific antigen on their cell surface (tumorspecific transplantation antigen (TSTA) or in the nucleus (T antigen) DNA oncogenic viruses • Adenoviridae • Herpesviridae – Epstein-Barr virus • Poxviridae • Papovaviridae – Human papillomaviruses • Hepadnaviridae – Hepatitis B RNA oncogenic viruses • Retroviridae – Leukemia virus Viruses to treat cancer • • • • • • • Adenovirus (H101) Talimogene laherparepvec (T-VEC) Reolysin Delta 24 cold virus Modified measles Modified herpesvirus Modified HIV 16 10/30/2016 Viral infections Latent and persistent viral infections • A latent viral infection is one in which the virus remains quiet or latent within a host cell and does not produce disease for an extended period, perhaps years • Persistent viral infections occur gradually over an extended period of time Fig. 13.21 Prions • Proteinaceous infectious particle • Cause diseases such as kuru, Creutzfeldt-Jakob disease, fatal familial insomnia, mad cow disease, scrapie which are characterized by spongiform encephalopathies • Disease is caused by the conversion of a normal host glycoprotein (PrPC) into an infectious form (PrPSc) 17 10/30/2016 Plant viruses and viroids • Plant viruses are morphologically similar to animal viruses and have similar types of nucleic acids • Because of the presence of the plant cell walls, viruses typically gain access through wounds or are assisted by other parasites (nematodes, fungi, insects) • Some plant diseases are caused by viroids, which consist of naked RNA Fig. 13.22 18