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96 Cards in this Set

  • Front
  • Back

Dimitri Iwanowsk

Russian botanist - mosaic tobacco



Walter Reed

Yellow Fever

Fredrick Twort & Felix D'Herelle

Bacteriophage

What happened in 1931

Electron microscopes allow the observation of Viruses

What is a Virus

Genetic elements that replicate independently of the host's chromosome but not independently of the cells themselves

Characteristics of Viruses

- Either DNA or RNA, double or single stranded genomes


- no cytoplasmic membrane


- no Cytosol


- no organelles


- Outermost layer provides protection and recognition sites for host cells


** Cannot carry out metabolic pathways or replicate in absence of host cell



Extracellular State

Virion



Intracellular State

Capsid removed - exist as a nucleic acid

Naked Viron

Only nucleic Acid and Proteins are present - Called nucleocapsid

Nucleocapsid

Naked viron - only nucleic acid and protein are present

Capsid

Protects the genome


Gives shape to virus


Made up of protein subunits called Capsomeres


Organization of capsomeres give viruses symmetry


Involved in the attachment of the host cell

Capsomeres

Protein subunit of a capsid


Number of capsomeres is a characteristic for specific virus



Herpes Virus

162 Capsomeres



Adenovirus

252 Capsomeres

All viruses have

NUCLEOCAPSID

Enveloped Virus

Acquired from host cells during viral replication or release

Envelope is a

Portion of membrane system of host but not function of cytoplasmic membrane ei: endocytosis etc

Envelope is composed of

Phospholipid bilayer and proteins



Envelopes proteins and glycoproteins

Play a role in host recognition

Enveloped Virus with helical Capsid Model



Helical Capsid


Matrix Protein


Envelope


Glyco proteins

3 shapes of Viruses

Helical


Polyhedral


Complex

Viral Taxonomy and Classification

Not classified using hierarchical system due to relationship between viruses are not well understood


- Names derived from characteristics


- Based on: Genome, shape, presence of envelope and size of virion





Class of Virus and Genome

DNA: ss DNA/ds DNA


RNA: ssRNA/ dsRNA


RNA&DNA: ssRNA (retroviruses)/dsDNA(hepadnaviruses)

Replication of viruses

Dependent of host enzymes and organelles to produce new virions


- Lack gene for all the enzymes needed to replicate


- Lack ribosomes for protein synthesis

Lytic

Replication cycle results in death and lysis of host cell



Lysogenic

a dormant state within the host

Viral replication steps

Attachment


Entry


Biosynthesis


Assembly


Release of assembled particles

Attachment

Uses tail pins and legs to attach to the surface of the outer membrane

Entry

Sends a string of T4 genome down through outer membrane, peptidoglycan and cytoplasmic membrane

How it looks

Capsid head full of DNA, Sheath leading down (body), Tail fibers (look like legs), Base plate and pins leading out of it

Viral Replication During Lytic Cycle time map

attachment:0


Entry:5 mins


Synthesis and assembly : 5-25 min.


Burst time: @25mins


Release of virons by lysis: 25-27~mins



Lysogeny

aka Lysogenic cycle or temperate phage


modified replication cycle


infected host cells grow and reproduce normally for generations before they lyse

Prophage

Inactive Phage


- viral genome incorporated into host genome but viral proteins are not actively being produced

Transduction

When phages transfer bacterial DNA that has been incorporated into phage genome into infected host cells.


- one of the mechanisms of horizontal gene transfer

Animal Viruses VS Bacteriophage

Same basic replication pathway as bateriophage


Differences in attachment/entry,release, and site of replication


- differences result from: Envelope around some viruses and the Eukaryotic nature of animal cells (lack cell walls)

Attachment of Animal Viruses

Attachement of animal viruses


- utilizes specific ligand - receptor interactions


- do NOT have tails or tail fibers


- have glycoprotein spikes or other attachment molecules that mediate attachment



Surface receptors of Animal Viruses

Look like spikes on viral surface


Enzymes like the neuraminidase- essential in viral maturation and budding



Hemagglutinin

Plays a key role in adsorption and penetration of the host

Three mechanisms of entry

1. Direct penetration - capsid stick into membrane and sends out a viral genome ei: poliovirus (naked)


2. Membrane Fusion - Glyco protein fuses to cell membrane and enzyme breaks down the bottom part that touches then a viral genome is released by the uncoating capsid ei:HIV (enveloped)


3. Endocytosis - whole virus is engulfed then its membrane is broken down and the enveloped virus is released, uncoated then viral genome is released ei: Influenza (evveloped)

Synthesis of Animal Viruses

- each type requires different strategy depending on its nucleic acid


- DNA often enters the nucleus


- RNA often replicate in cytoplasm



Positive single strand RNA acts like:

mRNA

Synthesis of dsDNA virus of animals

dsDNA viruses - similar to replication of host cellular DNA, viral genome replicated in the nucleus and the viral proteins made in the cytoplasm

Synthesis of ssDNA

Cells do not use ssDNA


parvoviruses have ssDNA genome


- host enzymes produce DNA strand complementary to viral genome to form dsDNA molecule


dsDNA used for viral replication and transcription

most DNA viruses enter:

in nucleus and assembled in cytoplasm



most RNA viruses develop

solely in cytoplasm

Naked Viruses are released by:

Exocytosis or lysis



Enveloped viruses cause:

Persistant infections - years with no activity

Latent virus/provirus

Animal viruses that remain dormant in host cell


- may be years with no viral activity


- typical of enveloped viruses


- differences from lysogeny of bacteriophage


- some latent viruses do not become incorportated into chormosome


- incorporation of provirus into host DNA is rpemanent no induction in eukaryote (HIV)

Retrovirus

RNA virus


do NOT use their genomes as mRNA


carry its enzyme called Reverse Transcriptase that use viral NA to synthesize single stranded DNA


DNA used as template to for a complementary


DNA strand by DNA polymerase - forms double stranded DNA


dsDNA mirgrates into nucleus and is incorporated into host genome by another retrovirus enzyme called an Integrase



Integrase

Retrovirus enzyme

Retrovirus migration

Double stranded DNA migrates into cell nucleus and integrates into host cell genomic DNA (provirus)


- VIRAL DNA IS PERMANENTLY INCORPORATED INTO HOST DNA ei: HIV

Epidemiology of Aids

First recognized in homo men in USA


Now world wide


Found in blood, semen, saliva, and vagina secretions and breast milk


- Blood and semen most infective


- infected fluid must be injected or contact a tear in the skin or mucous membrane

HIV Target Cells

target white blood cells - CD4 aka helper T


cell death by


- killing via virus induced cyto-lysis


- killing of infected cells by HIV specific CD8 killer T cells


CD4 are key immune cells and depletion impairs function of the immune system

Most deaths due to AIDS are actually due to

Mycoses


- infection with various fungi partly define end stage AIDS


- pnumonea indicative of end stage of AIDS



Treatment for enveloped positive ssRNA viruses with Reverse Transcriptase

Cocktail of antiviral drugs


- does not cure infection but can reduce viral load to undetectable levels and patient can live normal life while on treatment

Potential outcome of Host cell interaction and Viral infection

- cell destruction and necrosis


- No cell destruction


- latent infection


- Tumor transformation

Viruses are repsonsible for % of human cancers

20-25%

Cancer

The uncontrolled reproduction of cells result in the formation of a tumour


- Benign - not cancerous


- Malignant - Cells multiply too quickly and spread all over the body - metastasis

Cancer causing Viruses

Herpes - cervical


Epstein Barr - lymphoma - tumour of Jaw


HPV - cervical


Human T cell - Leukemia

Oncogene Theory

- Cancer causing genes are in DNA in inactive form


- found in a veriety of organisms


- proto-oncogenes function in regulating growth and cellular devision


- Converted to oncogenes by carcinogens: virus radiation and chemicals


- oncogenes present in certain viruses and can cause cancer when incorporated into host cell

Virus Killing Cancer Cells

2015 - first approved


- genetically engineered Herpes simplex Virus type 1.


- produces a granulocyte-macrophage colony - stimulating factor - cytokine that recruits immune system to tumour site


- used for localized treatment of unresponsive/inoperable skin melanomas

How does IMLYGIC work

Targets and replicates within tumor cell


Causes cell lysis or death which ruptures tumours releasing tumour derived antigen which may promote an antitumour immune response



PRION

infectious protein


- Transmissible spongiform encephalopathies (TSE)


- Normal cellular prion protein (PrPc) are present in all uninfected brains


- abnormal prion found in infected brain PrPsc



How Prion disease works

Caused my misfolding of proteins. Spread when PrPsc interacts with normal PrP and causes it to adopt the incorrectly folded state. This continues until all PrP are in the PrPsc form


sprial to straight*



What happens in the brain from Prions

- PrPsc are very resistant to chemicals


- clump together


- taken up by lysosomes


- cant break it down so it bursts the cell leaving lesions in the brain tissue


- free mutants are taken up by other cells and the cycle continues



Resevoirs of infection and 3 types

Site where pathogens are maintained as a source of infection


- Animal Reservoir


- Human Carriers


- Nonliving Reservoir



Animal reservoir

Zoonoses: disease naturally spread from animal host to human


- Direct contact with animal or its waste


- eating animals


- bloodsucking arthropods


humans are dead end host for zoonotic pathogens



Human Carriers

- infected but asymptomatic and can infect others


- Some can eventually get sick but some never do


Healthy carriers may have a defensive system that protects them


ei: TB, AIDS

Non Living reservoir

Soil, water and food


- some may be contaminated due to feces or urine - E coli



Emerging viruses

Viruses that appear for the first time in a population or has rapidly expanded its host range


ei: Zika, West Nile, Ebola, SARS

Hemorrhagic Fevers

Enveloped, unsegmented Negative ssRNA Viruses


- Marburg and Ebola virus are causes


Natrual resevoir and mode of trasmission to humans is unknown


- spread from person to person from contamination


- Virons attack many cells of the body * Macrophages and liver cells


- uncontrolled bleeding under skin and from every body opening


- up to 90% die


- Only treatment: Fluid replacement

Ebola

Largest in history - west africa


- first case reported in March 2014


- Outbreak over March 29 2016

Ebola Pathology

- Enters patient through mucous membrane, breaks in the skin or parenterally


- infects: monocytes, macrophages, dendritic cells, epithelial cells, endothelial cells, fibroblasts, hepatocytes and andrenal cortical cells


- Incubation period


- 6 days injection/10 days contact


- fatality 70%; 61% if hospitalized

Ebola Treatment

- No treatment


- Clinical management = supportive care of complications


- Recommended care: volume repletion, maintenance of BP, nutritional support





Zmapp

Ebola experimental treatment


- intravenous cocktail with 3 humanized monoclonal antibodies - targets surface of glycoproteins on virus and prevents attachment


- worked in 5/7 ppl but not sig. enough



TKM

Experimental Ebola treatment


- interfering RNA that targets 3 of 7 Ebola proteins


- RNA targets viral RNA for degradation in the cell



Merck Vaccine

developed in Canada


- live virus that expresses the ebola surgace glycoprotein


- works with 100% efficiency

Flu virus is called

Orthomyxoviridae

Viruses that infect animals but transfer to humans

Bunyaviridae and Arenaviridea

Influenza

Caused by orthomyxovirus A and B


- rarely attacks cells outside the lungs


- 8 different ssRNA molecules


- envelope studded with two glycoproteins


- nuraminidase(NA): enables viral release by hydrolyzing sialic acid residues from surface


- Hemagglutinin(HA): binds to terminal sialic acid, attachmet to pulmonary epithelial cells trigger endocytosis of virus

Nueraminidase(NA)

- One of main surgace antigens on influenza virus


- inhibition of enzyme prevents viral maturation



Antigenic drift

Mutation

Antigenic Shift

recombination

Mutation

Antigenic Drift

Recombination

Antigenic shift

Influenza mutations

Result in new strains of influenza virus


- often in Asia due to dense pop and domesticated birds and pigs

Influenza and the world

New pandemic could involve 1/3 of worlds population


viruses multiply in epithelial cell lining in the lung


- death of infected cells eliminate the lungs epithelial lining


- patients more susceptible to secondary bacterial infections



Epidemiology of Influenza

- infection primarily through inhalation of airborne viruses


- millions infected in US yearly


- about 64,000 die anually

Prevention and Treatment of Influenza

Treatment: Oseltamivir- blocks virion release from infected cells


- must be administered within 48hrs


Prevention:


- Immunization

Zika Virus infection methods

- Transmitted by mosquitos bites, and sexual contact with someone infected


- Viral RNA can be found in saliva, breast milk and urine.


- unclear if these can cause infection


- in semen up to 76 days post infection



Flavivirus

Suspected host for Zika is non human primate

Zika structure

Enveloped virus

Zika Replication

- receptors not well characterized


- internalize via endocytosis


- vesicles fuse with endosome and uncoating takes place


- ssRNA genome replicated within spherules made with endoplasmic reticulum


- single polyprotein synthesized and inserted in ER membrane


- cleaved into individual protein


- immature virons assembled in the ER


- transit to Golgi where they are processed into mature virions


- transit to membrane where they are released - persistent infection

Symptoms of Zika

Same as flu


- sever for pregnant women's babies: Microcephaly and gulliain - Barre syndrom


GB syndrom- not well understood. Auto immune disease targeting peripheral nerves - weakness, tingling sensation in extremities

Zika and Epidemiology

Zika has been know about for aprox 64-67 years


- not known to cause birth defects until current outbreak in Brazil and Central America


- unclear why its causing more sever problems now

Hypothesis to why Zika became a pandemic

Evolution of virus make it spred more effectively by vector


- evolution of virus to increas viral load in humans thus increasing effective trasmission


- Immune system of Brazil and C.America are naive to it so more likely to get it