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Chapter 13 Characterizing and Classifying Viruses, Viroids, and Prions Characteristics of Viruses • Virus – Minuscule, acellular infectious agent having either DNA or RNA – Causes many infections of humans, animals, plants, and bacteria – Causes most of the diseases that plague the industrialized world 10/15/11 . MDufilho 2 Characteristics of Viruses • 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 (with one exception) • Have extracellular and intracellular state 10/15/11 MDufilho 3 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 10/15/11 MDufilho 4 Figure 13.1 Virions-overview 10/15/11 MDufilho 5 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 – dsDNA, ssDNA, dsRNA, ssRNA – Linear and segmented or single and circular – Much smaller than genomes of cells 10/15/11 MDufilho 6 Figure 13.2 The relative sizes of genomes Partial genome of E. coli 10/15/11 Viral genome MDufilho 7 Characteristics of Viruses • Hosts of Viruses – Most viruses infect only particular host’s cells – Affinity of viral surface proteins for proteins on host cell – May be so specific they infect only particular kind of cell in a particular host – Generalists – infect many kinds of cells in many different hosts 10/15/11 MDufilho 8 Figure 13.3 Hosts of viral infections-overview 10/15/11 MDufilho 9 Figure 13.4 Sizes of selected virions E. coli (bacterium) (1000 nm 3000 nm) Red blood cell (10,000 nm in diameter) Bacterial ribosomes (25 nm) Poliovirus (30 nm) Bacteriophage T4 (50 nm 225 nm) Bacteriophage MS2 (24 nm) 10/15/11 Smallpox virus (200 nm 300 nm) MDufilho Tobacco mosaic virus (15 nm 300 nm) 10 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 – Capsomere made of single or multiple types of proteins – Three basic shapes - helical,polyhedral,complex 10/15/11 MDufilho 11 Figure 13.5 The shapes of virions-overview 10/15/11 MDufilho 12 Figure 13.6 Bacteriophage T4-overview 10/15/11 MDufilho 13 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’s proteins and glycoproteins often play role in host recognition 10/15/11 MDufilho 14 Figure 13.7 Enveloped virion-overview 10/15/11 MDufilho 15 Table 13.2 Families of Human Viruses 10/15/11 MDufilho 16 Viral Replication • Lysogeny – Modified replication cycle – Infected host cells grow and reproduce normally for generations before they lyse – Temperate phages – Prophages – inactive phages – Lysogenic conversion results when phages carry genes that alter phenotype of a bacterium 10/15/11 MDufilho 17 Viral Replication • Replication of Animal Viruses – Same basic replication pathway as bacteriophages – Differences result from – Presence of envelope around some viruses – Eukaryotic nature of animal cells – Lack of cell wall in animal cells 10/15/11 MDufilho 18 Viral Replication • Replication of Animal Viruses – Attachment of animal viruses – Chemical attraction – Animal viruses do not have tails or tail fibers – Have glycoprotein spikes or other attachment molecules that mediate attachment – Uncoating – Direct penetration – Membrane fusion 10/15/11 MDufilho 19 Viral Replication • Replication of Animal Viruses – Synthesis of animal viruses – 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 10/15/11 MDufilho 20 Figure 13.13 Synthesis of proteins and genomes in animal RNA viruses-overview 10/15/11 MDufilho 21 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 10/15/11 MDufilho 22 Figure 13.14 The process of budding in enveloped viruses Enveloped virion Budding of enveloped virus Viral glycoproteins Cytoplasmic membrane of host Viral capsid 10/15/11 MDufilho 23 Viral Replication • Replication of Animal Viruses – Latency of animal viruses – When animal viruses remain dormant in host cells – May be prolonged for years with no viral activity – Some latent viruses do not become incorporated into host chromosome – Incorporation of provirus into host DNA is permanent 10/15/11 MDufilho 24 The Role of Viruses in Cancer • Animal’s genes dictate that some cells can no longer divide or 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 vs. malignant tumors – Metastasis – Cancers 10/15/11 MDufilho 25 Figure 13.16 The oncogene theory of the induction of cancer in humans Normal state: DNA Protooncogene Represses Gene for repressor mRNA Repressor Result: No cancer First “hit”: Virus inserts promoter DNA Oncogene Represses Gene for repressor mRNA Repressor Result: Still no cancer Second “hit”: Virus inserts into represssor gene DNA Oncogene mRNA 10/15/11 Protein No repressor protein because gene is segmented MDufilho Causes cell division Result: Cancer 26 The Role of Viruses in Cancer • Environmental factors that contribute to the activation of oncogenes – – – – Ultraviolet light Radiation Carcinogens Viruses 10/15/11 © 2012 Pearson Education Inc. MDufilho 27 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 ~15% of human cancers – Burkitt’s lymphoma – Hodgkin’s disease – Kaposi’s sarcoma – Cervical cancer 10/15/11 MDufilho 28 Are Viruses Alive? • Some consider them complex pathogenic chemicals • Others consider them the least complex living entities – Use sophisticated methods to invade cells – Have the ability to take control of their host cell – Are able to replicate themselves 10/15/11 MDufilho 29 Other Parasitic Particles: Viroids and Prions • Characteristics of Viroids – Extremely small, circular pieces of RNA that are infectious and pathogenic in plants – Similar to RNA viruses, but lack capsid – May appear linear due to H bonding 10/15/11 MDufilho 30 Figure 13.20 The RNA strand of the small potato spindle tuber viriod (PSTV) Genome of bacteriophage T7 10/15/11 PSTV MDufilho 31 Figure 13.21 One effect of viroids on plants 10/15/11 MDufilho 32 Other Parasitic Particles: Viroids and Prions • Characteristics of Prions – Proteinaceous infectious agents – Cellular PrP protein – Made by all mammals – Normal structure with -helices called cellular PrP – Prion PrP – Disease-causing form with -pleated sheets called prion PrP – Prion PrP changes shape of cellular PrP so it becomes prion PrP 10/15/11 MDufilho 33 Other Parasitic Particles: Viroids and Prions ANIMATION Prions: Overview 10/15/11 MDufilho 34 Other Parasitic Particles: Viroids and Prions • Characteristics of Prions – Normally, nearby proteins and polysaccharides force PrP into cellular shape – PrP mutations result in formation of prion Pr 10/15/11 MDufilho 35 Other Parasitic Particles: Viroids and Prions ANIMATION Prions: Characteristics 10/15/11 MDufilho 36 Other Parasitic Particles: Viroids and Prions • Characteristics of Prions – Prion diseases – Fatal neurological degeneration, fibril deposits in brain, and loss of brain matter – Large vacuoles form in brain – Characteristic spongy appearance – Spongiform encephalopathies – Prions only destroyed by incineration or autoclaving in 1 N NaOH 10/15/11 MDufilho 37 Other Parasitic Particles: Viroids and Prions ANIMATION Prions: Disease 10/15/11 MDufilho 38 Viral Diseases of the Skin and Wounds • Herpes Infections – Signs and symptoms – Slow spreading skin lesions – Recurrence of lesions is common – Pathogen and virulence factors – Caused by human herpesviruses 1 and 2 – Produce various proteins that act as virulence factors – Pathogenesis – Painful lesions caused by inflammation and cell death – Cause fusion of cells to form syncytia 10/15/11 MDufilho 39 Figure 19.11 Oral herpes lesions 10/15/11 MDufilho 40 Viral STDs • Genital Herpes – Signs and symptoms – Small blisters on or around the genitals or rectum – Pathogen and virulence factors – Human herpesvirus 2 causes most cases – Virus can become latent in nerve cells – Pathogenesis – Herpesvirus kills epithelial cells at infection site – Blisters may form at sites far from initial infection site – Babies can become infected during birth 10/15/11 MDufilho 41 Figure 24.12 Herpes lesions of the eyes and skin-overview 10/15/11 MDufilho 42 Viral Diseases of the Skin and Wounds • Herpes Infections – Epidemiology – Spread between mucous membranes of mouth and genitals – Herpes infections in adults are not life threatening – Diagnosis, treatment, and prevention – Diagnosis made by presence of characteristic lesions – Immunoassay reveals presence of viral antigens – Chemotherapeutic drugs help control the disease but do not cure it 10/15/11 MDufilho 43 Viral Diseases of the Skin and Wounds • Warts – Benign epithelial growths on the skin or mucous membranes – Can form on many body surfaces – – – – – Various papillomaviruses cause warts Most warts are harmless Transmitted via direct contact and fomites Diagnosed by observation Various techniques to remove warts – New warts can develop due to latent viruses 10/15/11 MDufilho 44 Figure 19.13 Various kinds of warts--lesions caused by papillomaviruses-overview 10/15/11 MDufilho 45 Figure 24.13 Genital warts 10/15/11 MDufilho 46 Viral STDs • Genital Warts – Signs and symptoms – Warts on the genitalia and surrounding areas – Large growths called condylomata acuminata may form – Pathogen – Caused by human papillomaviruses (HPV) – HPV can cause various cancers 10/15/11 MDufilho 47 Viral STDs • Genital Warts – Pathogenesis and epidemiology – HPVs invade skin or mucous membranes during sex – Most common STD in the U.S. – Diagnosis, treatment, and prevention – Diagnosis made by presence of warts – Variety of methods available to remove warts – Vaccine available against HPV strain associated with cervical cancer 10/15/11 MDufilho 48 Viral Diseases of the Skin and Wounds • Chickenpox and Shingles – Signs and symptoms – Chickenpox characterized by lesions on the back and trunk that spread across body – Shingles lesions localized to skin along an infected nerve – Pathogen – Varicella-zoster virus (VZV) causes both diseases – Pathogenesis – Infected dermal cells cause rash characteristic of chickenpox – Virus becomes latent in nerve ganglia – Reactivated VZV causes shingles 10/15/11 MDufilho 49 Viral Diseases of the Skin and Wounds • Chickenpox and Shingles – Epidemiology – Chickenpox occurs mostly in children – Disease is more severe in adults – Risk of shingles increases with age – Diagnosis, treatment, and prevention – Diagnosis based on characteristic lesions – Treatment based on relief of symptoms – Vaccine available against chickenpox 10/15/11 MDufilho 50 Viral Diseases of the Skin and Wounds • Other Viral Rashes – Erythema infectiosum – Caused by an erythrovirus of family Parvoviridae – Respiratory disease that manifests as a rash – Also referred to as fifth disease – Roseola – Caused by human herpesvirus 6 (HHV-6) – Characterized by a rose-colored rash – Coxsackievirus infection – Caused by coxsackie A viruses – Produces lesions like those from herpes infections – Also causes hand-foot-and-mouth disease 10/15/11 © 2012 Pearson Education Inc. MDufilho 51 Figure 19.16 A case of erythema infectiosum (fifth disease) 10/15/11 MDufilho 52 Viral Diseases of the Nervous System • Viruses more readily cross the bloodbrain barrier • Occur more frequently than bacterial and fungal infections • Include meningitis, polio, rabies, and encephalitis 10/15/11 MDufilho 53 Viral Diseases of the Nervous System • Viral Meningitis – Signs and symptoms – Similar to those of bacterial meningitis – Usually milder than those of bacterial or fungal meningitis – Pathogens and virulence factors – 90% of cases caused by viruses in the genus Enterovirus – Pathogenesis – Damage to cells in the meninges triggers meningitis 10/15/11 MDufilho 54 Viral Diseases of the Nervous System • Viral Meningitis – Epidemiology – More common than bacterial and fungal meningitis – Spread via respiratory droplets and feces – Diagnosis, treatment, and prevention – Diagnosed by characteristic signs and symptoms in the absence of bacteria in the CSF – No specific treatment exists 10/15/11 MDufilho 55 Viral Diseases of the Nervous System • Arboviral Encephalitis – Arboviruses are arthropod-borne viruses – Transmitted via blood-sucking arthropods (e.g., mosquitoes) – Mosquito-borne arboviruses can cause arboviral encephalitis – As zoonotic diseases, they rarely affect humans – Arboviruses usually cause mild, coldlike symptoms – Can cause if cross the blood-brain barrier 10/15/11 MDufilho 56 Table 20.2 Characteristics of Arboviral Encephalitis Diseases and Viruses in the United States 10/15/11 MDufilho 57 Figure 20.15 Transmission of six encephalitis arboviruses Humans can be infected via mosquito bites. Small mammals are hosts for VEE and California viruses only. Mosquitoes are vectors. Encephalitis arboviruses can overwinter inside mosquito eggs. Wild birds Horses, Domestic fowls and rarely other domestic mammals are hosts for equine viruses. 10/15/11 MDufilho Birds are hosts for all six encephalitis arboviruses. 58 Figure 20.16 Human West Nile virus encephalitis in the United States Reported cases Number of reported cases Annual deaths (299) (124) (264) (84) (86) (43) (30) (9) Time (months/years) 10/15/11 MDufilho 59 Viral Diseases of the Nervous System • Arboviral Encephalitis – Diagnosis based on signs and symptoms – Confirmed by presence of arbovirus-specific antibodies in CSF – Treatment is supportive – Prevention involves limiting contact with mosquitoes – Use netting and insect repellents – Eliminate stagnant water – Vaccines for horses available against EEE, WEE, VEE, and WNV 10/15/11 MDufilho 60 Viral Cardiovascular and Systemic Diseases • Infectious Mononucleosis – Signs and symptoms – Severe sore throat and fever occur initially – Followed by swollen lymph nodes, fatigue, appetite loss – Pathogen and virulence factors – Epstein-Barr virus (EBV or HHV-4) is the causative agent – EBV establishes latent infection in host – EBV implicated in number of other diseases 10/15/11 MDufilho 61 Figure 21.13 Diseases associated with Epstein-Barr virus Diseases of EBV Oral hairy leukoplakia* Burkitt’s lymphoma (shown) Chronic fatigue syndrome* Nasopharyngeal cancer Asymptomatic Infectious mononucleosis Lacking Poor Normal Vigorous State of cellular immunity *EBV implicated, not proven 10/15/11 MDufilho 62 Viral Cardiovascular and Systemic Diseases • Infectious Mononucleosis – Pathogenesis and epidemiology – Transmission occurs via saliva – EBV infects B lymphocytes – Majority of adults have antibodies against EBV – Diagnosis, treatment, and prevention – Diagnosed by presence of large, lobed B lymphocytes and neutropenia – Treatment focuses on relieving symptoms – Prevention is difficult since EBV occurrence is widespread 10/15/11 MDufilho 63 Viral Cardiovascular and Systemic Diseases • Cytomegalovirus Disease – Signs and symptoms – Asymptomatic in most cases – Complications in neonates and immunodeficient individuals – Pathogen and virulence factors – Caused by Cytomegalovirus – Pathogenesis and epidemiology – Transmit by direct contact with body fluids or transplacentally – One of the most common infections of humans – Diagnosis, treatment, and prevention – Fomivirsen is administered for eye infections – No vaccine is available 10/15/11 MDufilho 64 Figure 21.14 An abnormally enlarged “owl’s eye” cell indicates Cytomegalovirus (CMV) infection “Owls eye” cell 10/15/11 MDufilho 65 Viral Cardiovascular and Systemic Diseases • African Viral Hemorrhagic Fever – Signs and symptoms – Fever and fatigue – Minor petechiae progress to severe internal hemorrhaging – Pathogens and virulence factors – Caused by Ebolavirus or Marburgvirus – Pathogenesis and epidemiology – Occurs primarily in Africa – Transmitted via contact with bodily fluids of infected individual 10/15/11 MDufilho 66 Figure 21.17 Filamentous Ebolavirus 10/15/11 MDufilho 67 Figure 21.18 Sites in which locally acquired cases of Marburg and Ebola viruses have occurred Marburg 10/15/11 Ebola MDufilho 68 Viral Cardiovascular and Systemic Diseases • African Viral Hemorrhagic Fever – Diagnosis, treatment, and prevention – Diagnosis based on characteristic symptoms and presence of virus in the blood – Treatment involves fluid and electrolyte replacement – Vaccines are being studied for their effectiveness in humans 10/15/11 MDufilho 69 Viral Diseases of the Upper Respiratory System • Common Cold – Signs and symptoms – Sneezing, runny nose, congestion, – sore throat, malaise, and cough – Pathogens and virulence factors – Enteroviruses (rhinoviruses) are the most common cause – Numerous other viruses cause colds – Pathogenesis – Cold viruses replicate in and then kill infected cells 10/15/11 MDufilho 70 Viral Diseases of the Upper Respiratory System • Common Cold – Epidemiology – Rhinoviruses are highly infective – Spread by coughing/sneezing, fomites, or person-to-person contact – Diagnosis, treatment, and prevention – Signs and symptoms are usually diagnostic – Pleconaril can reduce duration of symptoms – Hand antisepsis is important preventive measure 10/15/11 MDufilho 71 Viral Diseases of the Lower Respiratory System • Influenza – Signs and symptoms – Sudden fever, pharyngitis, congestion, cough, myalgia – Pathogens and virulence factors – Influenza virus types A and B are the causative agents – Mutations in hemagglutinin and neuraminidase produce new strains – Occurs via antigenic drift and antigenic shift 10/15/11 MDufilho 72 Figure 22.12 Influenzavirus budding from a cell Neuraminidase Hemagglutinin Envelope ssRNA molecule in helical capsid 10/15/11 MDufilho 73 Viral Diseases of the Lower Respiratory System • Influenza – Mutations in hemagglutinin and neuraminidase produce new strains – Occurs via antigenic drift and antigenic shift – Named by type (A or B), location and date or original identification – Example – A/Singapore/1/80 (H1N2) – If isolated from an animal, that is included – Hong Kong flu or swine flu – Asia is major site of antigentic shift 10/15/11 MDufilho 74 Figure 22.13 The development of new strains of flu viruses-overview 10/15/11 MDufilho 75 Figure 22.11 A scene from the flu pandemic of 1918-19 10/15/11 MDufilho 76 Viral Diseases of the Lower Respiratory System • Influenza – Pathogenesis – Symptoms produced by the immune response to the virus – Flu patients are susceptible to secondary bacterial infections – Virus causes damage to the lung epithelium – Epidemiology – Transmitted via inhalation of viruses or by selfinoculation – Complications occur most often in the elderly, 10/15/11 MDufilho with chronic diseases children, and individuals 77 Viral Diseases of the Lower Respiratory System • Influenza – Diagnosis, treatment, and prevention – Signs and symptoms during a community-wide outbreak are often diagnostic – Treatment involves supportive care to relieve symptoms – Oseltamivir and zanamivir can be administered early in infection – Prevent by immunization with a multivalent vaccine 10/15/11 MDufilho 78 Viral Diseases of the Lower Respiratory System • Severe Acute Respiratory Syndrome (SARS) – Signs and symptoms – High fever, shortness of breath, and difficulty breathing – Later develop dry cough and pneumonia – Pathogen and virulence factors – Caused by a coronavirus called SARS virus – Pathogenesis and epidemiology – SARS virus spreads via respiratory droplets – Diagnosis, treatment, and prevention – Diagnosis based on signs and symptoms of SARS 10/15/11 – Treatment is supportive MDufilho 79 Figure 22.14 The face of SARS 10/15/11 MDufilho 80 Viral Diseases of the Lower Respiratory System • Respiratory Syncytial Virus Infection – Most common childhood respiratory disease – Signs and symptoms – Fever, runny nose, and coughing in babies or immunocompromised individuals – Mild coldlike symptoms in older children and adults – Pathogen – Respiratory syncytial virus (RSV) – Pathogenesis – Virus causes syncytia to form in the lungs to RSV further damages the lungs 10/15/11 – Immune response MDufilho 81 Figure 22.15 A syncytium forms when RSV triggers infected cells to fuse with uninfected cells Multinucleated syncytium Newly infected cell Nucleus RSV Infected host cell Uninfected cell Newly infected cell Infected host cell RSV Multinucleated syncytium 10/15/11 MDufilho 82 Viral Diseases of the Lower Respiratory System • Respiratory Syncytial Virus Infection – Epidemiology – Transmission occurs via close contact with infected persons – Diagnosis, treatment, and prevention – Diagnosis made by immunoassay – Supportive treatment for young children – Prevention includes aseptic technique of health care and day care employees 10/15/11 MDufilho 83 Viral Diseases of the Digestive System • Viral Gastroenteritis – Signs and symptoms – Similar to bacterial gastroenteritis – Pathogens and pathogenesis – Caused by caliciviruses, astroviruses, and rotaviruses – Epidemiology – More cases occur in winter – Diagnosis, treatment, and prevention – Serological test distinguishes among viruses – Treatment is based on fluid and electrolyte replacement exists 10/15/11 – Vaccine for rotavirus MDufilho 84 Figure 23.13 Some viruses causing gastroenteritis-overview 10/15/11 MDufilho 85 Figure 23.14 Deaths from rotaviral diarrhea are most common in developing countries 1000 deaths 10/15/11 MDufilho 86 Viral Diseases of the Digestive System • Viral Hepatitis – Signs and symptoms – Jaundice, abdominal pain, fatigue, vomiting, appetite loss – Symptoms may occur years after initial infection – Host immune response causes much of the liver damage – Pathogen and pathogenesis – Hepatitis A virus (HAV) – Hepatitis B virus (HBV) – Hepatitis C virus (HCV) – Hepatitis delta virus (HDV) – Hepatitis E virus (HEV) 10/15/11 MDufilho 87 Table 23.2 Comparison of Hepatitis Viruses 10/15/11 MDufilho 88 Viral Diseases of the Digestive System • Viral Hepatitis – Diagnosis, treatment, and prevention – Initial diagnosis made by observation of jaundice, enlarged liver, or fluid in the abdomen – Serological testing can identify viral antigens – HBV diagnosed by presence of viral proteins in body fluids – Supportive care for symptoms – Prevent with good hygiene and protected sex or abstinence – Vaccines are available against HAV and HBV 10/15/11 MDufilho 89 Figure 23.15 The three types of viral particles produced by hepatitis B viruses-overview 10/15/11 MDufilho 90