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Chapter 13 Viruses General Characteristics of all viruses • Contain a single type of nucleic acid (DNA or RNA) • Contains a protein coat that surrounds the nucleic acid – Capsid: most of mass of cell (subunit=capsomers) – May be enclosed by envelope (part of host’s plasma membrane); may be covered with spikes Viruses • Obligate intracellular parasites – Inert outside of living tissue (host) – In host Æ nucleic acids active and multiply • Are viruses the only obligate intracellular parasites? • Most viruses infect only specific types of cells in one host; Host range is determined by specific host attachment sites and cellular factors 1 Medical Significance • Most agents that would interfere with viral multiplication would also harm the host cells and would be very toxic History began with the Tobacco Mosaic Virus (TMV) • 1886 Aldolf Mayer showed that a virus was transmissable between plants • 1892 Iwanowski tried to isolate it by filtering with porcelain filter Sizes of viruses 2 Polyhedral virus • Capsid coat made of capsomeres • Nucleic acid inside Helical virus with an envelope • The shape is a long rod • Rabies and Ebola are helical viruses • Influenzae virus is helical with an envelope Helical Viruses Figure 13.4a, b 3 Bacteriophage: Complex virus Bacterial viruses • • Known as bacteriophages or phages Two different life cycles 1. Lytic cycle-results in lysis of the cell 2. Lysogenic cycle-may result in lysis of the cell or the virus becomes a permanent part of the chromosome by integrating (Lytic Cycle) • Attachment • Penetration • Biosynthesis • Maturation • Release Phage attaches by tail fibers to host cell Phage lysozyme opens cell wall, tail sheath contracts to force tail core and DNA into cell Production of phage DNA and proteins Assembly of phage particles Phage lysozyme breaks cell wall 4 Lytic Cycle • Burst Time: time from phage attachment to release (about 20 -40 min) • Burst size: number of new phages released from a single cell (50 – 200) Lytic Cycle Lytic Cycle 5 Growth curve of bacteriophage Lysogenic Cycle • Lysogenic (temperate) – Phage may result in lysis of cell – Virus may integrate into host chromosome and become permanent part of cell • Phage remains inactive within lysogenic host cells • Cells then immune to reinfection by same virus • Phage conversion: host cell may have new characteristics due to phage Lysogenic Cycle 6 Specialized transduction Bacterial DNA Prophage gal gene 1 Prophage exists in galactose-using host (containing the gal gene). Galactose-positive donor cell gal gene 2 Phage genome excises, carrying with it the adjacent gal gene from the host. gal gene 3 Phage matures and cell lyses, releasing phage carrying gal gene. 4 Phage infects a cell that cannot utilize galactose (lacking gal gene). Galactose-negative recipient cell 5 Along with the prophage, the bacterial gal gene becomes integrated into the new host’s DNA. 6 Lysogenic cell can now metabolize galactose. Galactose-positive recombinant cell Figure 13.13 How can you study bacteriophages? • Plaque assay -pour agar with bacteria and phage on top of an agar plate -“plaque” develops where virus infected bacterial cell -each plaque is counted as one virus Growing Animal Viruses • Animal viruses may be grown in living animals or in embryonated eggs. Figure 13.7 7 Growing Viruses • Animal and plants viruses may be grown in cell culture. – Continuous cell lines may be maintained indefinitely. Figure 13.8 Virus Identification • Cytopathic effects(CPE): can count like plaques • Serological tests – Detect antibodies against viruses in a patient – Use antibodies to identify viruses in neutralization tests, viral hemagglutination, and Western blot • Nucleic acids Cytopathic Effect of Viruses Figure 13.9 8 Multiplication of Animal viruses • Attachment Viruses attaches to cell membrane (receptors are inherited) • 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 (usually results in cell death) Attachment, Penetration, and Uncoating Figure 13.14 Release of an enveloped virus by budding Figure 13.20 9 DNA Papovavirus 1 Virion attaches to host cell 7 Virions are released Host cell DNA Capsid 2 Virion penetrates DNA cell and its DNA is uncoated Cytoplasm 6 Virions mature Capsid proteins mRNA 5 Late translation; capsid proteins are synthesized 4 Late transcription; DNA is replicated 3 Early transcription and translation; enzymes are synthesized Figure 13.15 RNA Virus Multiplication • RNA viruses differ in how mRNA produced + single stranded RNA can serve as mRNA to code for proteins = single stranded RNA does not code for proteins Retroviruses: reverse transcriptase RNA Figure 13.17 10 Retrovirus Capsid Reverse transcriptase DNA Virus Two identical + stands of RNA 1 Retrovirus penetrates host cell. Host cell DNA of one of the host cell’s chromosomes 5 Mature retrovirus leaves host cell, acquiring an envelope as it buds out. Reverse transcriptase Viral RNA Identical strands of RNA 2 Virion penetrates cell and its DNA is uncoated 4 Transcription of the provirus may also occur, producing RNA for new retrovirus genomes and RNA that codes for the retrovirus capsid and envelope proteins. Viral proteins RNA Provirus 3 The new viral DNA is tranported into the host cell’s nucleus and integrated as a provirus. The provirus may divide indefinitely with the host cell DNA. Figure 13.19 • Latent Viral Infections – Virus remains in asymptomatic host cell for long periods • Cold sores, shingles • Persistent Viral Infections – Disease processes occurs over a long period, generally fatal • Subacute sclerosing panencephalitis (measles virus) Virus Families • Single-stranded DNA, nonenveloped viruses – Parvoviridae • Human parvovirus • Fifth disease – Anemia in immunocompromised patients 11 Double-stranded DNA, nonenveloped viruses • Mastadenovirus – Respiratory infections in humans – First isolated in adenoids – Tumors in animals Double-stranded DNA, nonenveloped viruses • Papillomavirus (human wart virus) • Polyomavirus – Cause tumors, some cause cancer Double-stranded DNA, nonenveloped viruses • Orthopoxvirus (vaccinia and smallpox viruses/ variola) • Molluscipoxvirus – Smallpox, molluscum contagiosum, cowpox 12 DNA Animal Viruses • Poxviridae – dsDNA, enveloped – small pox virus (variola) • Simplexvirus (HHV1 and HHV 2) • Varicellavirus (HHV 3) • Lymphocryptovirus (HHV 4) • Cytomegalovirus (HHV 5) • Roseolovirus (HHV 6) • HHV 7 • Kaposi's sarcoma (HHV 8) – Some herpesviruses can remain latent in host cells Herpes simplex-1 • HHV-1 causes fever blisters, HHV-2 genital herpes • Symptoms: fluid filled skin lesions • Treatment: Acyclovir 13 Varicella (chickenpox) and Herpes Zoster (Shingles) • HHV-3 causes chicken pox and latent activation known as shingles • Acquired by respiratory route, 2 weeks later see vesicles on skin • Vaccine established in 1995 for chickenpox Epstein Barr • Causes infectious mononucleosis • Acquire by saliva, incubation period is 4-7 weeks • Identify by -lobed lymphocytes -heterophile antibodies -fluorescent antibody tests Double-stranded DNA, nonenveloped viruses • Hepadnavirus (Hepatitis B virus) – Use reverse transcriptase to produce DNA from mRNA 14 Hepadnaviridae • dsDNA, enveloped • Hepatitis B -passes through intermediate stage (RNA) -three particles in blood Dane filamentous sphericle -exposure through blood/body fluids Hepatitis B • Incubation period is ~12 weeks • 10% of cases become chronic, mortality rate is less than 1% • About 40% of the chronic cases die of liver cirrhosis RNA animal viruses • Is there an enzyme in animal cells to replicate RNA? • What does RNA polymerase do? 15 RNA animal viruses • (+) single stranded RNA viruses – RNA serves as mRNA to code for proteins • (-) single stranded RNA viruses – RNA does not code for proteins RNA Figure 13.17 Single-stranded RNA, + strand, nonenveloped • Enterovirus – Enteroviruses include poliovirus and coxsackievirus • Rhinovirus • Hepatitis A virus 16 Picornaviridae (+) ssRNA • Poliovirus • Virus ingested then travels throughout the body • In some cases it impairs the upper motor neurons, less than 1% of all cases • Vaccines – Salk vaccine (IPV) – Enhanced-inactivated polio (E-IPV) – Sabin vaccine Cases of Poliomyelitis in US Picornaviridae (+) ssRNA • Rhinovirus -causes the common cold -100 or more serological types -virus grows best in the nose and conjunctiva 17 Picornaviridae (+) ssRNA • Enterovirus responsible for 90% of viral gastroenteritis – Rotavirus • Most common cause of viral gastroenteritis – Norwalk-like virus • Responsible for local epidemics Rotavirus • Note the shape which gave it the name rota=wheel Picornaviridae (+) ssRNA • Hepatitis A -obtain through fecal-oral route, enters GI tract and multiplies -incubation period is ~4 weeks -symptoms include: anorexia, malaise, nausea, diarrhea, abdominal discomfort, fever, and chills lasting 2-21 days 18 Single-stranded RNA, + strand, nonenveloped • Arboviruses can replicate in arthropods; include yellow fever, dengue, SLE, and West Nile viruses • Hepatitis C virus Flaviviridae (+) ssRNA, enveloped • Hepatitis C virus – Obtain from blood/body fluids – Incubation period averages 6 weeks – Hard to screen blood for the virus – 85% of all cases become chronic Single-stranded RNA, – strand, one RNA strand • Vesiculovirus • Lyssavirus (rabies virus) – Cause numerous animal diseases 19 Rhabdoviridae (-)ssRNA, enveloped • Rabies virus -enters the skin and multiplies in skeletal muscle and connective tissue -virus travels along nerves to the CNS causing encephalitis Pathology of rabies Single-stranded RNA, – strand, one RNA strand • Filovirus – Enveloped, helical viruses – Ebola and Marburg viruses 20 Single-stranded RNA, – strand, one RNA strand • Paramyxovirus • Morbillivirus – Paramyxovirus causes parainfluenza, mumps and Newcastle disease • Influenzavirus (Influenza viruses A and B) • Influenza C virus – Envelope spikes can agglutinate RBCs Orthomyxoviridae-multiple strands of (-)RNA • Influenza virus – Consists of 8 segments of RNA – Envelope has H spikes (hemagglutinin) and N spikes (neuraminidase) – Incubation is 1-3 days – Symptoms include: chills, fever, headache, muscle aches, may lead to cold-like symptoms 21 Influenza virus Identical (+) strands RNA • Lentivirus (HIV) • Oncogenic viruses – Use reverse transcriptase to produce DNA from viral genome – Includes all RNA tumor viruses Retroviridae-multiple strands of (+)RNA • HIV 22 Retroviruses • HIV, Hepatitis B • Reverse Transcriptase Retrovirus Capsid Reverse transcriptase DNA Virus Two identical + stands of RNA 1 Retrovirus penetrates host cell. Host cell DNA of one of the host cell’s chromosomes 5 Mature retrovirus leaves host cell, acquiring an envelope as it buds out. Reverse transcriptase Viral RNA Identical strands of RNA 2 Virion penetrates cell and its DNA is uncoated 4 Transcription of the Viral proteins RNA provirus may also occur, producing RNA for new retrovirus genomes and RNA that codes for the retrovirus capsid and envelope proteins. Provirus 3 The new viral DNA is tranported into the host cell’s nucleus and integrated as a provirus. The provirus may divide indefinitely with the host cell DNA. Figure 13.19 Cancer • Activated oncogenes transform normal cells into cancerous cells. • Transformed cells have increased growth, loss of contact inhibition, tumor specific transplant and T antigens. • The genetic material of oncogenic viruses becomes integrated into the host cell's DNA. 23 Oncogenic Viruses • Oncogenic RNA viruses • Oncogenic DNA Viruses – Retroviridae – Adenoviridae – Heresviridae – Poxviridae – Papovaviridae – Hepadnaviridae • Viral RNA is transcribed to DNA which can integrate into host DNA • HTLV 1 • HTLV 2 Prions • Infectious proteins • Inherited and transmissible by ingestion, transplant, & surgical instruments • Spongiform encephalopathies: Sheep scrapie, Creutzfeldt-Jakob disease, GerstmannSträussler-Scheinker syndrome, fatal familial insomnia, mad cow disease • PrPC, normal cellular prion protein, on cell surface • PrPSc, scrapie protein, accumulate in brain cells forming plaques Prions PrPSc PrPc 1 2 3 4 Lysosome Endosome 5 6 7 8 Figure 13.21 24