Chapter13 Characterizing and Classifying Viruses, Viroids, and Prions

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Chapter13 Characterizing and Classifying Viruses, Viroids, and Prions 11/20/2017 MDufilho 1

Characteristics of Viruses Viruses Minuscule, acellular, infectious agent having either DNA or RNA Cause infections of humans, animals, plants, and bacteria Cause most of the diseases that plague the industrialized world Cannot carry out any metabolic pathway Neither grow nor respond to the environment Cannot reproduce independently Recruit the cell's metabolic pathways to increase their numbers No cytoplasmic membrane, cytosol, organelles Have extracellular and intracellular state 11/20/2017 MDufilho 2

Characteristics of Viruses Extracellular state Called virion Protein coat (capsid) surrounding nucleic acid Nucleic acid and capsid also called nucleocapsid Some have phospholipid envelope Outermost layer provides protection and recognition sites for host cells Intracellular state Capsid removed Virus exists as nucleic acid 11/20/2017 MDufilho 3

Characteristics of Viruses Genetic Material of Viruses Show more variety in nature of their genomes than do cells Primary way scientists categorize and classify viruses May be DNA or RNA, but never both Can be dsdna, ssdna, dsrna, ssrna May be linear and segmented or single and circular Much smaller than genomes of cells 11/20/2017 MDufilho 4

Characteristics of Viruses Hosts of Viruses Most viruses infect only particular host's cells Due to affinity of viral surface proteins for complementary proteins on host cell surface May be so specific they only infect particular kind of cell in a particular host Generalists infect many kinds of cells or many different hosts All types of organisms are susceptible to some virus 11/20/2017 MDufilho 5

Characteristics of Viruses Capsid Morphology Capsids Provide protection for viral nucleic acid Means of attachment to host's cells Composed of proteinaceous subunits called capsomeres Viral Shapes Capsomere may be made of single or multiple types of proteins Viruses can be classified by virion shape Three basic types of viral shapes: Helical Polyhedral Complex 11/20/2017 MDufilho 6

Figure 135 The shapes of virions Enveloped capsid Fiber layer Cell's vesicle 11/20/2017 MDufilho 7

Characteristics of Viruses The Viral Envelope Acquired from host cell during viral replication or release Envelope is portion of membrane system of host Composed of phospholipid bilayer and proteins Some proteins are virally coded glycoproteins (spikes) Envelope proteins and glycoproteins often play role in host recognition Enveloped viruses are more fragile than naked viruses 11/20/2017 MDufilho 8

Classification of Viruses Virus classification based on: Type of nucleic acid Presence of an envelope Shape Size Viral genera have only been organized into families Relationship among viruses is not well understood by taxonomists 11/20/2017 MDufilho 9

Viral Replication Dependent on hosts' organelles and enzymes to produce new virions Lytic replication Viral replication usually results in death and lysis of host cell Five stages of lytic replication cycle: Attachment Entry Synthesis Assembly Release 11/20/2017 MDufilho 10

Figure 1312 Three mechanisms of entry of animal viruses Viral genome inside capsid Empty capsid Cytoplasmic membrane of host engulfs virus (endocytosis) Receptors on cytoplasmic membrane Direct penetration Viral genome Viral glycoproteins Envelope Viral glycoproteins remain in cytoplasmic membrane Viral genome Uncoating capsid Endocytosis Receptors on cytoplasmic membrane of host Viral genome Uncoating capsid Membrane fusion 11/20/2017 MDufilho 11

Viral Replication Replication of Animal Viruses Synthesis of DNA Viruses of Animals Each type of animal virus requires different strategy depending on its nucleic acid DNA viruses often enter the nucleus RNA viruses often replicate in the cytoplasm Must consider How mrna is synthesized What serves as template for nucleic acid replication 11/20/2017 MDufilho 12

Viral Replication Synthesis of DNA Viruses of Animals dsdna viruses Similar to replication of cellular DNA Viral genome replicated in the nucleus Viral proteins are made in the cytoplasm Some exceptions ssdna viruses Hepatitis B viruses replicate DNA from an RNA intermediary Cells do not use ssdna Parvoviruses have ssdna genomes DNA strand folds back on itself to form dsdna, which is replicated by cellular DNA polymerase Newly replicated strand is released as ssdna 11/20/2017 MDufilho 13

Figure 1313 Synthesis of proteins and genomes in animal RNA viruses +ssrna virus Receptors on cytoplasmic membrane of host ssrna virus Receptors on cytoplasmic membrane of host Receptors on cytoplasmic membrane of host dsrna virus +ssrna ssrna dsrna Transcription by viral RNA polymerase Transcription by RNA-dependent RNA transcriptase Unwinding Complementary ssrna to act as template Further transcription Copies of +ssrna Translation of viral proteins; genome acts as mrna Further transcription Copies of ssrna Complementary +ssrna to act as template and as mrna Translation of viral proteins ssrna Transcription by viral RNA polymerase to make complementary RNA strands +ssrna acts as template and as mrna Translation of viral proteins Assembly Assembly Assembly Positive-sense ssrna virus Negative-sense ssrna virus Double-stranded RNA virus 11/20/2017 MDufilho 14

Viral Replication Replication of Animal Viruses Assembly and Release of Animal Viruses Most DNA viruses assemble in nucleus Most RNA viruses develop solely in cytoplasm Number of viruses produced depends on type of virus and size and initial health of host cell Enveloped viruses cause persistent infections Naked viruses are released by exocytosis or lysis 11/20/2017 MDufilho 15

Viral Replication Replication of Animal Viruses Latency of Animal Viruses When animal viruses remain dormant in host cells Viruses are called latent viruses or proviruses May be prolonged for years with no viral activity Incorporation of provirus into host DNA is permanent 11/20/2017 MDufilho 16

The Role of Viruses in Cancer Cell division is under strict genetic control Genes dictate that some cells can no longer divide at all Cells that can divide are prevented from unlimited division Genes for cell division "turned off" or genes inhibiting division "turned on" Neoplasia Uncontrolled cell division in multicellular animal Mass of neoplastic cells is tumor Benign versus malignant tumors Malignant tumors also called cancers Metastasis occurs when tumors spread 11/20/2017 MDufilho 17

The Role of Viruses in Cancer Protooncogenes promote cell growth and division Uncontrolled activation of oncogenes can lead to cancer Environmental factors that contribute to the activation of oncogenes: Ultraviolet light Radiation Carcinogens Viruses 11/20/2017 MDufilho 18

Figure 1316 The oncogene theory of the induction of cancer in humans Normal state: DNA Protooncogene Gene for repressor Represses mrna Repressor Result: No cancer First "hit": Virus inserts promoter DNA Oncogene Gene for repressor Represses mrna Repressor Result: Still no cancer Second "hit": Virus inserts into repressor gene DNA Oncogene mrna No repressor protein because gene is segmented 11/20/2017 Protein Causes cell MDufilho division Result: Cancer 19

The Role of Viruses in Cancer Viruses cause 20 25% of human cancers Some carry copies of oncogenes as part of their genomes Some promote oncogenes already present in host Some interfere with tumor repression Specific viruses are known to cause some human cancers: Burkitt's lymphoma Hodgkin's disease Kaposi's sarcoma Cervical cancer 11/20/2017 MDufilho 20

Other Parasitic Particles: Viroids and Prions Characteristics of Viroids Extremely small, circular pieces of ssrna that are infectious and pathogenic in plants Similar to RNA viruses, but lack capsid Viroid RNA does not code for proteins Viroid RNA adheres to complementary plant RNA Plant enzyme degrades the dsrna Results in a disease state 11/20/2017 MDufilho 21

Other Parasitic Particles: Viroids and Prions Characteristics of Prions Proteinaceous infectious agents Cellular PrP Made by all mammals Normal, functional structure has α-helices Prion PrP Disease-causing form has β-sheets Prion PrP causes cellular PrP to refold into prion PrP 11/20/2017 MDufilho 22

Prions: Overview PLAY Prions: Overview 11/20/2017 MDufilho 23

Prions: Characteristics PLAY Prions: Characteristics 11/20/2017 MDufilho 24

Other Parasitic Particles: Viroids and Prions Characteristics of Prions Prion diseases Spongiform encephalopathies Large vacuoles form in brain Characteristic spongy appearance BSE, scrapie, kuru, CWD, vcjd Transmitted by ingestion, transplantation, or contact of mucous membranes with infected tissues No standard treatment for any prion disease 11/20/2017 MDufilho 25

Other Parasitic Particles: Viroids and Prions Characteristics of Prions Normal sterilization procedures do not deactivate prions Prions destroyed by incineration or autoclaving in concentrated sodium hydroxide European Union recently approved use of enzymes to remove prions from medical equipment 11/20/2017 MDufilho 26

Prions: Diseases PLAY Prions: Diseases 11/20/2017 MDufilho 27