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What is a virus?
- -discovered in 1898
- -Visualized only after discover of electron microscope in 1930
- -A virus particle is also called a virion
- -smaller than bacteria
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How are viruses unique?
- -Their simple, very small, acellular
- -The presence of either DNA or RNA, not both, in the same viral particle
- -Their inability to reproduce independently of living, 2-50 genes.
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What is a virus composed of?
- -DNA or RNA and protein capsid which surrounds the nucleic acid
- -Combo of nucleic acid and capsid is called a nucleocapsid
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What is a naked virus?
- -If it only has a protein capsid, it is naked
- -The subunits are call capsomeres and the entire protein coat is called the capsid
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What is an envelope virus?
- -Membrane derived from host cell
- -in the envelope are viral proteins.
- -Enveloped viruses are not very stable since envelope is it is a membrane.
- -The envelope has protein and carbs, some from the host.
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What are the parts of a naked viruses?
- -Capsid
- -Nucleic acid
- -Capsomere
- -Nucleocapsid
- -Virion
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What are the parts of an envelope virus?
- -Capsid
- -Nucleic acid
- -Capsomere
- -Nucleocapsid
- -Virion
- -Envelope
- -Spike (envelope glycoproteins)
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What is the genetic makeup of a virus?
- -DNA or RNA
- -Single or Double stranded
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What are of the shapes of a viral capsid?
- -Icosahedral (hexagonal, most common)
- -Helical (spiral staircase-shaped)
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What is the viral growth rate?
- -Viruses make separate parts within the host cell they are infecting and then assemble into many viral particles
- -1 Human virus (12-72) = 100,00 virions
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What can a virus infect?
- -Animal: Influenze
- -Plant: Tobacco mosaic virus
- -Bacteria viruses: Bacteriophage
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Why study viruses?
- -Viral diseases have been some of the major concern for epidemics in humans. (Polio, rabies, smallpox, yellow fever)
- -Leading cause of all human disease (Common acute respiratory, GI, Ebola, AIDS, Hepatitis C, Hantaviruses, SARS)
- -Can be useful for gene therapy
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What are some viral diseases?
-Measles, Mumps, Chicken pox (shingles, reactivation of diseases), small pox.
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What is the effect of viral infections on cells?
- - Visible effects on the patient
- 1. Direct damage of virus to cells, make cells different
- 2. Host defense mechanisms (immunocytopathology) Sickness caused by immune system working
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What are the visible effects of viral pathology at the cellular level?
- -Cell death
- -Giant Cell formation, Syncytia
- -Rounding up of cells
- -Pilling up of cells
- -Inclusion boides inside the cells
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What is cell death?
- -CPE, cytopathic effect
- -Lysis of host cell, viral plaques, bacteriophage
- -Plaque assay of bacteriophage
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What is giant cell formation?
- -CPE, cytopathic effect
- -Syncytia, when cells fuse together to form large cells with many nuclei
- -Sticks to the T cells so they cannot kill anymore
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What is round up of cells?
- -III of viral CPE.
- -Rounded up as result of infection
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What is pilling up of cells?
- -CPE IV, Transformation, focus formation, wart
- -Warts are small, painless growth
- -Raised round or oval growth on the skin
- -No discomfort unless in a bad area, goes away on their own within two years
- -Venereal warts can cause cancer
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What is inclusion bodies?
- -CPE V
- -Visible by EM
- -Lesion inside the cell
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What is the life cycle of a virus?
- 1. Attachment
- 2. Penetration
- 3. Uncoating
- 4. Replication of Nucleic acids
- 5. Protein synthesis
- 6. Assembly
- 7. Release
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What is attachment?
- -1 step in life cycle
- -Lock and key, matching part
- -Attachment proteins, specific surface proteins for each virus
- -Cell specific-receptors
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What is penetration?
- -Life cycle step 2, follows attachment
- -Same step in bacteriophage with uncoating
- 1. Endocytosis-Whole virus goes in and then the capsule is released
- 2. Membrane fusion- just capsule is released
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What is uncoating?
- Step 3 of life cycle
- -Removal of membrane and capsid proteins, usually carried out by cellular enzymes that chew off the viral coat by lysosome function
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What is replication of nucleic acids?
- -Step 4 of the life cycle
- -DNA virus: nucleus, 1-2 viral and many cellular enzymes
- -RNA virus: cytoplasm, always uses viral coded enzymes
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What is protein synthesis?
- -Step 5 of life cycle
- -Cytoplasm, both viruses use cellular ribosomes and the rest of the host cell protein synthetic machinery
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What is assembly?
- -Step 6 of life cycle
- -Nucleic acid and capsid proteins come together and undergo self assembly which is a spontaneous process
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What is release?
- -Final step of life cycle
- -Lysis of cell, naked virus
- -Budding: enveloped virus: reverse process of membrane fusion. The virus acquires the membrane from the host cell but the membrane always contains viral protein that are required for specific attachment.
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What are the portals of viruses into the body?
- -Skin: HPV, Warts
- -Respiratory tract: Rhinovirus, common cold
- -GI tract: Rotavirus, diarrhea
- -Eye: Adenovirus, conjunctivitis
- -Genitourinary tract: Herpes virus, genital herpes
- -Direct entry: West nile, Hep B, Rubella, HIV
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What is the host-virus interaction?
- -Spread of virus throughout the body-viremia-target organ
- 1. Local replication at the site of entry, grow into large number
- 2. Spread into blood, viremia
- 3. Dissemination throughout the body-now any susceptible organ may be infected, can go in the lymphatic system to spread
- 4. Disease: Symptoms are usually seen in cells of only the target organ. Observable clinical symptoms
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When are we asymptomatic?
-After exposure to the virus, asymptomatic until the virus reaches the target organ and cause symptoms, and this is called the incubation time (period) of the virus.
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What is the incubation period?
-The amount of time between infection with a virus or bacteria to beginnings of the symptoms
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What does the incubation period depend on?
- -Distance between the site of infection and target organ. Short: 2 days for Flu, respiratory tract is both. Long: Weeks to months for rabies virus.
- -Growth rate of the virus. Fast: 1 to 2 for flu. Slow: weeks to months for papillomavirus for warts
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What is an interferon?
- -Host defense
- -Innate
- -Alpha: PMNS and macrophages
- -Beta: produced by Fibroblasts
- -Gama: produced by CD4 T cells
- -Cellular protein
- -Can work by warning neighboring cells
- -Antiviral states in the neighboring cells: Degrades RNA, inhibit protein synthesis
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What is humoral response to viruses?
- -Host defense
- -Neutralizing antibodies
- -Opsonization
- -Complement fixation
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What is neutralizing antibodies?
- -Host defense
- -render virus harmless, coats virus particle, inhibit attachment, if partial binding-no penetration, attachment. Aggregation-reduction in virus infectivity
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What is opsonization?
- -Host defense
- -Enhancement of phagocytosis
- -Antibodies with virus attach to PMNs which kill the virus
- -Nk cells kill antibody coated viral particles by process of antibody dependent cellular cytotoxicity (ADCC)
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What is complement fixation?
- -Host defense
- -Activation of complement cascade
- -Component of complement C3 is an opsonin
- -Viral proteins present in infected cell membrane or viral envelope can by lysed by C6, 7, 8, which form the MAC attack
- -ONLY enveloped viruses
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What is the role of CD4 (helper) and CD8 (T killer cell)?
- -Cellular response, these cells act on virus infected cells, not directly on virus.
- -CD4 T cell: They recognize the new viral antigens, proliferate and produce cytokines that activate B cells to release neutralizing antiviral antibodies
- -Activate T killer cells.
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What is the importance of smallpox?
- -WHO started in 1967 to eradicate smallpox from the earth, gone by 1977.
- -Last naturally occurring in 1977, somalia.
- -National stockpile of vaccine in case of bioterrorism.
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What is a DNA vaccine?
- -Being tested
- -Get into patient cells and express the gene produce
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What are other viral vaccines?
- -Live attenuated, vaccinia
- -Killed- Flu
- -Sub- viral component: Hep B, Recombinant
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What are specific examples of human DNA viruses?
- 1. Herpes Viruses
- 2. Adenovirus: Conjunctivitis, diarrhea
- 3. Paravovirus: Pox virus
- 4. HPV, warts
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