Virology Chapter 13 PDF

Chapter 13 Viruses, Viroids, and Prions Copyright © 2010 Pearson Education, Inc. Lectures prepared by Christine L. Case  History ▪ 1892 Iwanowski was wor...

Chapter 13 Viruses, Viroids, and Prions Copyright © 2010 Pearson Education, Inc. Lectures prepared by Christine L. Case  History ▪ 1892 Iwanowski was working with diseased tobacco plants. ▪ He showed that the infectious material (tobacco mosaic virus) was filterable through a filter that stopped bacteria and not influenced by dilution ▪ How did viruses evolve? We don’t really know. But you can watch a summary of competing hypotheses https://www.youtube.com/watch?v=X31g5TB- MRo&t=323s Copyright © 2010 Pearson Education, Inc. General Characteristics of Viruses ▪ Obligatory intracellular parasites ▪ Infect all forms of life ▪ Contain DNA or RNA (single stranded or double) ▪ Genome can be segmented ▪ Contain a protein coat ▪ Some are enclosed by an envelope ▪ Some viruses have spikes/peplomers/surface proteins/envelope proteins ▪ Most viruses infect only specific types of cells in one host (limited host range) Copyright © 2010 Pearson Education, Inc. Virus Sizes Copyright © 2010 Pearson Education, Inc. Figure 13.1 Virion Structure ▪ Nucleic acid ▪ DNA or RNA ▪ Capsid ▪ Capsomeres ▪ Envelope ▪ Spikes Copyright © 2010 Pearson Education, Inc. Figure 13.2a Morphology of a Helical Virus Copyright © 2010 Pearson Education, Inc. Figure 13.4 Morphology of a Complex Virus Some Viruses can also be irregular Copyright © 2010 Pearson Education, Inc. Figure 13.5 Morphology of an Enveloped Virus Copyright © 2010 Pearson Education, Inc. Figure 13.3 Growing Viruses ▪ Viruses must be grown in living cells ▪ Bacteriophages form plaques on a lawn of bacteria ▪ Animal and plant viruses have to be grown in animals or plants themselves or in animal and plant cells. Copyright © 2010 Pearson Education, Inc. Figure 13.6 Growing Viruses ▪ Animal viruses may be grown in living animals or in embryonated eggs Copyright © 2010 Pearson Education, Inc. Figure 13.7 Growing Viruses ▪ Animal and plant viruses may be grown in the organism or in cell culture ▪ Continuous cell lines may be maintained indefinitely Copyright © 2010 Pearson Education, Inc. Figure 13.8 Virus Identification ▪ Serological tests ▪ Detect antibodies against viruses in a patient ▪ Use antibodies to identify viruses in neutralization tests, viral hemagglutination, and Western blot ▪ Nucleic acids ▪ RFLPs ▪ PCR Copyright © 2010 Pearson Education, Inc. Multiplication of Bacteriophages -The Lytic Cycle ▪ Attachment: Phage attaches by tail fibers to host cell ▪ Penetration: Phage lysozyme opens cell wall; tail sheath contracts to force tail core and DNA into cell ▪ Biosynthesis: Production of phage DNA and proteins ▪ Maturation: Assembly of phage particles ▪ Release: Phage lysozyme breaks cell wall Copyright © 2010 Pearson Education, Inc. Lytic Cycle of a T-Even Bacteriophage 1 2 3 Copyright © 2010 Pearson Education, Inc. Figure 13.11 Lytic Cycle of a T-Even Bacteriophage 4 Copyright © 2010 Pearson Education, Inc. Figure 13.11 Results of Multiplication of Bacteriophages ▪ Lytic cycle ▪ Phage causes lysis and death of host cell ▪ Lysogenic cycle ▪ Prophage DNA incorporated in host DNA ▪ Phage conversion ▪ Specialized transduction ANIMATION Viral Replication: Virulent Bacteriophages ANIMATION Viral Replication: Temperate Bacteriophages Copyright © 2010 Pearson Education, Inc. The Lysogenic Cycle Copyright © 2010 Pearson Education, Inc. Figure 13.12 Generalized Transduction 2 3 4 5 6 Copyright © 2010 Pearson Education, Inc. Figure 8.28 Specialized Transduction Copyright © 2010 Pearson Education, Inc. Figure 13.13 Multiplication of Animal Viruses ▪ Attachment: Viruses attach to cell membrane ▪ Penetration by endocytosis or fusion ▪ Uncoating by viral or host enzymes ▪ Biosynthesis: Production of nucleic acid and proteins ▪ Maturation: Nucleic acid and capsid proteins assemble ▪ Release by budding (enveloped viruses) or rupture Copyright © 2010 Pearson Education, Inc. Attachment, Penetration, Uncoating ▪ By receptor-mediated endocytosis (specific) ▪ By pinocytosis (general) Copyright © 2010 Pearson Education, Inc. Figure 13.14a Attachment, Penetration, Uncoating ▪ By fusion Copyright © 2010 Pearson Education, Inc. Figure 13.14b Multiplication of DNA Virus Incorrect! Copyright © 2010 Pearson Education, Inc. Figure 13.15 Sense Strand (+ Strand) RNA Virus Incorrect! Translation first!!! Copyright © 2010 Pearson Education, Inc. Figure 13.17a Antisense Strand (– Strand) RNA Virus Copyright © 2010 Pearson Education, Inc. Figure 13.17b Double-Stranded RNA Virus Copyright © 2010 Pearson Education, Inc. Figure 13.17c Multiplication of a Retrovirus Copyright © 2010 Pearson Education, Inc. Figure 13.19 Latent and Persistent Viral Infections Copyright © 2010 Pearson Education, Inc. Figure 13.21  How viruses cause disease ▪ 1. Lysing cells (necrotic cell death) − Viral-mediated lysis − Loss of host cell maintenance ▪ 2. Immune-mediated cell lysis ▪ 3. Programmed cell death (apoptosis) ▪ 4. Cell to cell fusion (polykaryocyte) ▪ 5. Tumor formation (transformation) Copyright © 2010 Pearson Education, Inc. Viruses and Cancer ▪ Viral infections increase cancer risk in several ways: ▪ Transfer of oncogenes − Activation of growth pathways − Inhibition of cell cycle control checkpoints ▪ Insertional mutagenesis ▪ Chronic inflammation and repair ▪ Immune system inhibition ▪ Oncogenes change normal cells into transformed cells that have increased growth and loss of contact inhibition. Copyright © 2010 Pearson Education, Inc. Oncogenic Viruses ▪ Oncogenic DNA ▪ Oncogenic RNA viruses viruses ▪ Adenoviridae ▪ Retroviridae ▪ Herpesviridae ▪ Viral RNA is ▪ Poxviridae transcribed to DNA, ▪ Papovaviridae which can integrate into host DNA ▪ Hepadnaviridae ▪ HTLV-1 ▪ HTLV-2 Copyright © 2010 Pearson Education, Inc.  Viral Treatment--General ▪ Nucleoside base analogues ▪ AZT - azidothymidine ▪ ddI - dideoxyinosine ▪ ddC – dideoxycytosine ▪ Non-nucleosidal viral enzyme inhibitors (if available) ▪ Acyclovir (herpes family) ▪ Saquinavir (retroviruses) ▪ Telaprevir (HCV) ▪ Palliative (supportive) care ▪ Hydration ▪ Steroids Copyright © 2010 Pearson Education, Inc. Taxonomy of Viruses ▪ Family names end in -viridae. ▪ Genus names end in -virus. ▪ Viral species: A group of viruses sharing the same genetic information and ecological niche (host). Common names are used for species. ▪ Subspecies are designated by a number. Copyright © 2010 Pearson Education, Inc. Taxonomy of Viruses ▪ Herpesviridae ▪ Retroviridae ▪ Herpesvirus ▪ Lentivirus ▪ Human herpes virus ▪ Human HHV-1, HHV-2, HHV-3 immunodeficiency virus HIV-1, HIV-2 Copyright © 2010 Pearson Education, Inc.  ANIMATION Viral Replication: Overview ANIMATION Viral Replication: Animal Viruses Copyright © 2010 Pearson Education, Inc. Papovaviridae ▪ Double-stranded DNA, nonenveloped viruses ▪ Papillomavirus − Human wart virus Copyright © 2010 Pearson Education, Inc. Table 13.2 Cutaneous Warts Copyright © 2010 Pearson Education, Inc.  Genital Warts −Caused by the human papilloma viruses (HPV). −Most common viral STI in USA(?) −Are over 60 antigenic types of HPV. −Types 6 and 11 most common −Types 16 and 18 associated with cancer −Some may promote cervical cancer (women) and throat cancer (males). −Vaccine available Copyright © 2010 Pearson Education, Inc. Poxviridae ▪ Double-stranded DNA, enveloped viruses ▪ Smallpox (variola) and Monkeypox -Killed millions in the old and new worlds -The first vaccine by Jenner -Eradicated by vaccination Copyright © 2010 Pearson Education, Inc. Figure 13.5b Smallpox Lesions Copyright © 2010 Pearson Education, Inc. Figure 21.10 Herpesviridae ▪ Double-stranded DNA, enveloped viruses ▪ Simplexvirus − HHV-1 = HSV-1 − HHV-2 = HSV-2 ▪ Cytomegalovirus (HHV-5) ▪ Kaposi's sarcoma (HHV-8) ▪ Herpesviruses can remain latent in host cells Copyright © 2010 Pearson Education, Inc. Figure 13.16b Herpes Diseases Herpes Simplex 2—STI Epstein Bar—Mononucleosis Varicella Zoster—Chickenpox and Shingles Feline herpes virus 1—Flu-like condition in cats Herpes Simplex 1--Fever blisters and cold sores Copyright © 2010 Pearson Education, Inc.  Herpes ▪ Species infect neurons with lifelong latency in ganglia ▪ Spread by extensive surface to surface contact ▪ Condoms less effective at prevention ▪ 40 million cases of urogenital herpes in USA ▪ Mostly HHV-2 but gHHV-1 does occur (10x less likely) ▪ Neonatal herpes (particularly HHV-5) ▪ Virus crosses the placenta and infects developing fetus. Can cause abortion, mental disability or defective sight and hearing of newborn. Copyright © 2010 Pearson Education, Inc. Hepadnaviridae ▪ Double-stranded DNA, enveloped viruses ▪ Hepatitis B virus ▪ Use reverse transcriptase Copyright © 2010 Pearson Education, Inc. Figure 25.15  Viral Hepatitis ▪ hepatitis Inflammation of the liver. ▪ Second most frequently reported infectious disease in USA. ▪ Are at least 5 viruses that cause hepatitis: − 1. Hepatitis A virus - HAV − 2. Hepatitis B virus – HBV (A major world health problem) − 3. Hepatitis C virus – HCV (A major world health problem) − 4. Hepatitis D virus - HDV − 5. Hepatitis E virus - HEV Copyright © 2010 Pearson Education, Inc.  Viral Hepatitis ▪ Infectious hepatitis (HAV and HEV) ▪ RNA viruses, not related, transmitted by fecal- oral route. −Replicates in intestines, to blood, to liver −Virus is shed in feces. Contaminates water and shell fish. −Incubation period is 2 to 6 weeks. −Symptoms: fever, headache, jaundice −Causes acute disease, not chronic. −Vaccine/IG treatment is available. Copyright © 2010 Pearson Education, Inc.  Viral Hepatitis ▪ HBV, a DNA virus (Hepadnaviridae) −Transmitted by blood and other body fluids. −Incubation period is 4 to 26 weeks. −Virus gets to liver. −Early symptoms: fever, joint pain, loss of appetite. Then, jaundice. −Becomes chronic in 10% of people. −Chronic infection increases cancer risk >200 fold −Vaccine available Copyright © 2010 Pearson Education, Inc.  Viral Hepatitis ▪ HCV, an RNA virus (Flaviviridae) − Similar pathology to HBV − Greater incidence of chronic infection − Fewer cases worldwide − Greater prevalence in USA − NO VACCINE Copyright © 2010 Pearson Education, Inc.  Chronic Viral Hepatitis--Treatment ▪ Treatment for chronic HBV and HCV ▪ A combination therapy of the following: − Nucleoside analogs (Ribavarin) − Pegylated interferon − Viral protease inhibitors (Telaprevir, Simeprevir, etc) *The cost for a 28-days supply of Simeprevir is $22,120 and a 12-week supply is $66,360. Thus, a typical 12-week treatment course of Simeprevir when used with a total of 24-weeks of peg interferon plus ribavirin will cost approximately $85,000. Copyright © 2010 Pearson Education, Inc. Picornaviridae ▪ Single-stranded RNA, + strand, nonenveloped ▪ Enterovirus − Poliovirus ▪ Rhinovirus − The common cold ▪ Hepatitis A virus − Infectious hepatitis Copyright © 2010 Pearson Education, Inc. Table 13.2  Poliovirus ▪ Poliomyelitis ▪ Caused by the poliovirus ▪ Is a picornavirus, a small, naked, icosahedral RNA- containing virus ▪ Acquired through digestive system. Spread via fecal-oral route. Replicates in intestinal mucosa or in nasopharynx. Virus is shed in feces. Goes from intestines to blood (viremia). Incubation period is 10 - 15 days. Copyright © 2010 Pearson Education, Inc.  Poliovirus ▪ Poliomyelitis, cont. ▪ Are four courses of the disease: −1. Subclinical infection −2. Minor disease −3. Aseptic nonparalytic meningitis −4. Paralytic disease ▪ Only about 1% of cases become paralytic. Copyright © 2010 Pearson Education, Inc.  Poliovirus ▪ Poliomyelitis, cont. ▪ In paralytic polio, virus gets into CNS and lyses nerve cells. Flaccid paralysis results. ▪ Two vaccine types are available. − Salk vaccine—inactivated virus, injected − Sabin vaccine—attenuated live virus, oral Copyright © 2010 Pearson Education, Inc. Copyright © 2010 Pearson Education, Inc. Flaviviridae ▪ Single-stranded RNA, + strand, enveloped ▪ Arboviral Encephalitis: Arboviruses are transmitted by arthropods; include Yellow Fever, Dengue, SLE, Zika, and West Nile viruses. ▪ Hepatitis C virus Copyright © 2010 Pearson Education, Inc. Clinical Focus, p. 223 Coronaviridae ▪ Single-stranded RNA, + strand, enveloped ▪ Upper respiratory infections ▪ Coronavirus ▪ SARS ▪ MERS ▪ COVID-19 (Wuhan) A great example of a newly emergent disease Copyright © 2010 Pearson Education, Inc. Rhabdoviridae ▪ Single-stranded RNA, – strand, one RNA strand ▪ Lyssavirus (rabies virus) Copyright © 2010 Pearson Education, Inc. Figure 13.18a Copyright © 2010 Pearson Education, Inc. Filoviridae ▪ Single-stranded RNA, – strand, one RNA strand ▪ Enveloped, helical viruses ▪ Ebola and Marburg viruses Copyright © 2010 Pearson Education, Inc. Figure 23.21 Paramyxoviridae ▪ Single-stranded RNA, – strand, one RNA strand ▪ Measles ▪ Mumps Copyright © 2010 Pearson Education, Inc. Table 13.2 Orthomyxoviridae ▪ Single-stranded RNA, – strand, multiple RNA strands ▪ Envelope spikes can agglutinate RBCs ▪ Influenzavirus (influenza viruses A and B) ▪ Influenza C virus Copyright © 2010 Pearson Education, Inc. Table 13.2  Avian Influenza Influenza rarely kills by itself Other opportunistic infections do. Vaccines are available H = hemagglutination protein N = neuraminidase protein Copyright © 2010 Pearson Education, Inc. Clinical Focus, p. 371 HIV and AIDS ▪ 1981: In United States, cluster of Pneumocystis and Kaposi's sarcoma discovered in young homosexual men ▪ The men showed loss of immune function ▪ GRID and the 4-H’s of infectious immunodefiency ▪ 1983: Discovery of virus causing loss of immune function ▪ HIV and AIDS Copyright © 2010 Pearson Education, Inc.  The Origin of HIV ▪ Crossed the species barrier into humans in Africa. ▪ Earliest known sample 1959 (Congo) ▪ Spread in Africa as a result of urbanization ▪ Spread worldwide through modern transportation and unsafe sexual practices ▪ A Norwegian sailor (and his family) all died of AIDS complications starting in 1974. Copyright © 2010 Pearson Education, Inc. Retroviridae ▪ Single-stranded RNA, 2 +RNA strands, produce DNA ▪ Use reverse transcriptase to produce DNA ▪ Lentivirus (HIV) − SIV − FIV ▪ Oncogenic viruses − Includes all RNA tumor viruses − HTLV − FeLV Copyright © 2010 Pearson Education, Inc. HIV Attachment Copyright © 2010 Pearson Education, Inc. Figure 19.13 The Stages of HIV Infection ▪ Phase 1: Asymptomatic or chronic lymphadenopathy ▪ Phase 2: Symptomatic; early indications of immune failure ▪ Phase 3: AIDS indicator conditions Copyright © 2010 Pearson Education, Inc. The Progression of HIV Infection Copyright © 2010 Pearson Education, Inc. Figure 19.16 Diseases Associated with AIDS ▪ Cryptosporidium hominis ▪ Pneumocystis jirovecii ▪ Toxoplasma gondii ▪ Pneumocystic pneumonia ▪ Isospora belli ▪ Histoplasma capsulatum ▪ Cytomegalovirus ▪ Cryptococcus neoformans ▪ Herpes simplex virus ▪ Candida albicans ▪ Varicella-zoster virus ▪ Kaposi’s sarcoma ▪ Mycobacterium tuberculosis ▪ Hairy leukoplakia ▪ M. avium-intracellulare ▪ Cervical dysplasia Non-Hodgkins Lymphoma, Cervical Cancer, and Kaposi Sarcoma are AIDS-defining malignancies Copyright © 2010 Pearson Education, Inc. Diagnostic Methods ▪ Seroconversion takes up to 3 months ▪ HIV antibodies detected by ELISA ▪ HIV antigens detected by Western blotting ▪ Plasma viral load (PVL) is determined by PCR or nucleic acid hybridization Copyright © 2010 Pearson Education, Inc.  HIV Transmission ▪ HIV survives 6 hours outside a cell ▪ HIV survives less than 1.5 days inside a cell ▪ Infected body fluids transmit HIV via ▪ Sexual contact ▪ Breast milk ▪ Transplacental infection of fetus ▪ Blood-contaminated needles ▪ Organ transplants ▪ Artificial insemination ▪ Blood transfusion Copyright © 2010 Pearson Education, Inc.  HIV Epidemiology ▪ Prevalence worldwide ▪ Estimated 37.9 million worldwide − US prevalence—0.3% − Men who have sex with men--15% US. − Mauritania—23% − Bangladesh--0.2% − Saudi Arabia—0.0% (nonsense) ▪ Incidence in US (new cases) ▪ Male to male, 69%. ▪ Hetero male, 7% ▪ Hetero female, 16% ▪ Drug users, 6% Copyright © 2010 Pearson Education, Inc. Worldwide Distribution of AIDS and HIV Copyright © 2010 Pearson Education, Inc. Figure 19.17 Preventing AIDS ▪ Use of condoms ▪ Use of sterile needles (IDUs) ▪ Circumcision ▪ Chemotherapy (HAART) ▪ PrEP—prexposure prophylaxis ▪ Health care workers use Universal Precautions ▪ Wear gloves, gowns, masks, and goggles ▪ Do not recap needles ▪ Risk of infection from infected needlestick injury is 0.3% Copyright © 2010 Pearson Education, Inc. Vaccine Difficulties ▪ Mutations ▪ Clades (different “strains” of virus) ▪ Antibody-binding sites “hidden” ▪ Infected cells not susceptible to CTLs ▪ Proviruses ▪ Latent viruses Copyright © 2010 Pearson Education, Inc. Chemotherapy ▪ HIV can be effectively treated. It is no longer a death sentence! ▪ Nucleoside reverse transcriptase inhibitors ▪ NRTIs ▪ Non-nucleoside reverse transcriptase inhibitors ▪ NNRTIs ▪ Protease inhibitors ▪ Fusion inhibitors Copyright © 2010 Pearson Education, Inc. HAART ▪ Highly active antiretroviral therapy ▪ Combinations of nucleoside reverse transcriptase inhibitors plus ▪ Non-nucleoside reverse transcriptase inhibitor or ▪ Protease inhibitor ▪ Dapivirine (NNRTI) vaginal ring ▪ Truvada (HIV prevention pill) (PrEP) ▪ Tenofovir (NRTI) ▪ Emtricitabine (NRTI) ▪ HIV+ patients have increased risk of several cancers and shorter life-span Copyright © 2010 Pearson Education, Inc. Survival with HIV Infection ▪ Exposed, but not ▪ Long-term infected nonprogressors ▪ CCR5 mutation ▪ HIV variants ▪ Effective CTLs ▪ Effective CTLs Berlin and London patients “cured” of HIV following bone marrow transplants, both with CCR5 variant donors Copyright © 2010 Pearson Education, Inc.  Laughing Cannibals and Mad Cows Kuru—The Science and the Sorcery https://www.youtube.com/watch?v=vw_tClcS6To ▪ Kuru disease of Fore people of New Guinea 1957-1959 ▪ Cannibalistic practices ▪ Slow acting infectious agent ▪ Scrapie in sheep and hamsters ▪ Mad cow disease in Europe ▪ Zombie deer disease Copyright © 2010 Pearson Education, Inc.  Prions ▪ Prion Proteinaceous infectious particle. ▪ Stanley Prusiner is leader in the field. ▪ Cause kuru and Creutzfeldt Jakob disease in humans; mad cow disease in cows, and scrapie in sheep. Are fatal, neurological diseases. ▪ A prion consists of only protein. Is infectious. Gets to brain, and converts normal protein to infectious protein. Copyright © 2010 Pearson Education, Inc.  Prions ▪ Cow (or other animal meat) is contaminated with prion protein. ▪ Humans (or other animal) ingests the contaminated meat. ▪ The prion protein gets to the brain of person or the animal. ▪ That person or other animal comes down with the degeneration of brain tissue. Copyright © 2010 Pearson Education, Inc. How a Protein Can Be Infectious Copyright © 2010 Pearson Education, Inc. Figure 13.22 Viroids ▪ Naked RNA (300 to 400 bp in length) ▪ Self-complementary and very stable ▪ Cause of plant diseases only (thus far) ▪ Do not produce proteins—just replicate And you thought Prions and Slime molds were strange! Copyright © 2010 Pearson Education, Inc.