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What is Gardasil?

9.1 General Properties of Viruses

•__________ made of ___________

surrounded by a _____________

•Only ______

•No nucleus, organelles, cytoplasm

•AKA virions
-obligate intracellular parasite, nucleic acid, protein coat

-replicate inside host
9.2 Nature of the Virion
Viral Components-

•Nucleic acid-________

–Can be___________

•Capsid-__________ surrounding nucleic acid

•Envelope-______________ surrounding the capsid of
-either DNA or RNA

-single-stranded or double stranded; linear or circular

-protein coat

-lipid bilayer
Capsid proteins are arranged to give virion symmetry
1._________
–Rod-shaped, protein subunits twist up
-Helical symmetry
2._______
–Roughly _____

–___ equilateral equilateral triangles or faces

•Complex viruses-

–Head- ________

–tail & _____
-Icosahedral symmetry

-spherical

-20

-genome surrounded by capsid

-tail fibers
•Enzymes- some viruses have 1 or more to help _____________

•Bacterial viruses
–Bacteriophage/phage- viruses that infect _____
-infect host cell or for replication of viral genome

-bacteria
PART II Growth and Quantification
9.3 The Virus Host; 9.4 Quantification of Viruses

•Must be grown with living host cells.
3 types of hosts:

1. Prokaryotes
–Ex- _______

2. Plants
–Ex- _________

3. Animals
–Ex- ________
-Bacteriophage lambda with E.Coli

-Tobacco mosaic virus with Tobacco

-HIV with lymphocytes
Quantification methods:
1. Animal infectivity
–Inject sensitive animals with ___________________

2. Plaque assay
–Used to count _________
-10-fold serial dilutions of viral sample, determine % survival

-bacterial & some animal viruses
(each plaque results from infection by a single virus particle)
PART III Viral Replication 9.5 – 9.7
1. Attachment to __________

2. Penetration of either _________
-specific receptor on host cell, usually a membrane protein

-whole virus (eukaryotic) or just its genome (prokaryotic)
3. Synthesis of nucleic acid and protein- host machinery replicates _________________

4. Assembly and packaging of structural _______________

5. Release-___________; new virions can infect new host cell
-viral genome & makes viral proteins

-subunits & genome into capsid

-Lysis of host cell or by budding
Viral Restriction and Modification by the Host

•Bacteria synthesize ____ as protection against viral invaders

–Restriction endonucleases _________

•Viruses can__________________ by the host’s restriction endonucleases
–Glucosylation
–Methylation
–Encode proteins to inhibit host restriction systems

•Host cells have similar means of protecting their DNA from __________
-enzymes

-cleave DNA at specific sequences

-modify their DNA to avoid digestion

-degredation by viral endonucleases
2 types of phage:
–_____
–______
Lytic
•simple life cycle

•_______________

•Eg. T4 which infects E. coli
-lytic
-lysogenic

-infect host, make copies of themselves, lyse the host cell
T4 life-cycle:
Attachment & penetration

•____ of T4 attach to cell wall

•T4 genome is 1 linear molecule of ________

•DNA is ______. Rest of phage _____
-Tail-fibers

-double stranded DNA

-inserted into host.
-remains outside host cell
Replication & synthesis of new proteins

•DNA is _______

•Resulting _____ is translated to make proteins for __________

•100’s of copies of ________

Assembly & release of viral particles

•DNA is inserted into _______

•Host cell is _____________
-transcribed

-mRNA, new viral heads & tails

-viral DNA are also made

-empty capsids & tails are added

-lysed to release viruses
Lysogenic phage/Temperate viruses- Fig 9.16

•Enter a state called _____-viral genome integrates into host chromosome & is replicated with host chromosome

•Don’t immediately make new phage particles

• The virus is called a _______, when its genome exists as part of host genome

• Bacterial host cells that harbor __________

•Eventually, new phage are made (lytic cycle occurs) and cells ______

•Induction of ____ --> _____ --> _______

•Ex. Lambda which infects E. coli
-lysogeny

-prophage

-prophages are called lysogens

-lyse

-prophage, lytic cycle, host cell lysis
The lambda life cycle- Lysogeny

•Lambda genome is _________

•Attaches to host cell wall & _______

•DNA is inserted into E. coli chromosome between the _________

•Lysogenic cell- __________

•When chromosome replicates, lambda DNA __________

•Regulation of lytic versus lysogenic events in lambda is controlled by several promoters and regulatory proteins.
-double-stranded linear DNA

-injects its DNA into cell

-gal & bio genes

-cell with lambda DNA in its chromosome

-replicates with it
Induction
•Change in__________________ causes lambda to come out of chromosome and form new viruses

•Hundreds of _______

•Viruses are ________
-environmental conditions

-lambda chromosomes are formed

-assembled then cell lyses to release viruses
Bacteriophage with different types of nucleic acids:
Single-stranded
•DNA phage
–Ex. _____
•RNA phage
–Ex. _____
–Single-stranded

–Used as ______

–Complementary copies are also made and used as _____________

–New phage RNA is packaged, cells _____
-M13

-MS2

-mRNA to make proteins

-templates for making more phage RNA
9.12 Overview of Animal Viruses
4 Types of infection by animal viruses:

1. Lytic
–Destruction of _____

2. Persistent

–New virions leave _____

–Cell does not ___, but remains ___ and will produce ______
-host cells

-host by budding

-die, infected, virions indefinately
3.Latent

–Virus is not _______

–Symptoms appear only when ________

4. Transformation

–Virus can change ________

–Genetic changes that regulate _____

–Benign or _____
-actively replicating, dormant

-virus emerges from latency

-normal cell into cancer cell

-growth

-malignant tumors
Animal viruses
•Can be single or double stranded _______
-DNA or RNA
RNA viruses

Positive-strand RNA viruses (SS)-___________

•Ex. poliovirus, coronaviruses & rhinoviruses (_______)

Negative-strand RNA viruses (SS)- _____________

•Ex. rhabdoviruses (rabies), Ebola virus, measles, influenza, RSV
-genomic RNA is used directly as mRNA for making proteins

-(cold viruses)

-genomic RNA does not serve directly as mRNA but is transcribed into a complement that functions as mRNA
Double-stranded RNA viruses-

•Reoviruses- __________

•Rotavirus- member of reovirus family, most common cause of ________
-only animal viruses with double stranded RNA

-infant diarrhea
DNA viruses
•parvoviruses- only group with _____

•herpesvirus group (DS) - causes ___,____,____

•Are able to remain _________ in the body for years, becoming _________

•poxvirus group (DS) causes smallpox (vaccinia), cowpox, & some tumors
-single-stranded DNA

-cold sores, venereal disease, chicken pox

-latent, active during stressful conditions
9.13 Retroviruses

•Retro means_____-

•Cause HIV & some forms of cancer

•Single stranded ______

•Enzyme __________

•DNA integrates into ________

•Viral DNA is transcribed into __________

•New viruses are assembled and released
-"backward"

-RNA genome

-reverse transcriptase copies RNA into DNA

-host genome like a temperate/lysogenic

-mRNA & RNA for new viruses
9.14 Viroids and Prions

Viroids

•Small, _____

•Mostly _____

Prions
•_____

•BSE (mad cow), scrapie (sheep), Creutzfeld-Jakob, kuru (humans), chronic wasting disease (deer, elk)
•Fig 9.29 Normal protein takes on
-naked ss RNA

-crop diseases

-Protein-only infectious agent
Control of Viruses and Eukaryotic Pathogens 20.10 Antiviral Drugs

Effective antiviral agents must target ______

Anti-HIV drugs:

•____

• Azidothymidine (AZT)

•______

–bind HIV protease, preventing the protease from processing viral polypeptides

•_____

–synthetic peptide that binds to an HIV membrane protein preventing the viral membrane from binding to the host cell membrane
-virus-specific enzymes and processes

-Reverse transcriptase inhibitor

-protease inhibitors

-fusion inhibitors
28.1 Public Health and Water Quality

•Prior to coliform counting procedures such as MPN technique, water was ________

•Fig 28.1 With the discovery that ___________ was an effective disinfectant, large water supplies could be treated.
-filtered to reduce turbidity

-chlorine
28.2 Wastewater and Sewage Treatment
•Sewage- liquid effluent contaminated with ___________

•Wastewater- from domestic sewage or industrial sources that must be treated to ___________

–so it can no longer support __________

–to eliminate _______
-human or animal fecal materials

-reduce organic & inorganic materials

-microbial growth

-potentially toxic materials
Primary wastewater treatment-Fig 28.3

•Uses ____________

•Water passes through ______, then is allowed to settle several hours

anoxic secondary wastewater treatment- fig 28.5

•Digestive & ______ of many bacteria

•Occurs in ___________
-physical seperation methods

-gates & screens

-fermentative reactions

-sludge digesters or bioreactions
aerobic secondary wastewater treatment- fig 28.6

•Digestive _____

•Can use _____________

Optional tertiary

•(chlorine, UV, O3) treatment before ?
-reactions of microbes

-tricling filter or activated sludge process
28.3 Drinking Water Purification- fig 28.8

•Drinking water plants- industrial size physical and chemical systems to ____________

•Clarification- ______

•Filtration

•Disinfection-

–Usually by _____
-remove contaminants from water sources to make the water potable

-suspended solids are coagulated & removed

-chlorination
•UV radiation as an
____________
– physical not chemical

–short ________

–no _____
-alternative to chlorine for disinfection

-contact time

-by-products
•Table 28.1 & 28.2 - Sources of waterborne pathogens: ______

•Worldwide, lack of water treatment facilities and access to clean water _________
-Drinking water or Recreational water

-contribute to the spread of infectious diseases
Pathogenic _____________

•Vibrio cholerae
– Cholera
•Salmonella typhi
–typhoid fever Legionella pneumophila
–Legionellosis (Legionnaires’ Disease)
-bacteria killed by chlorine treatment
Vibrio cholerae- cholera

•Gram ______

•Major waterborne disease; mainly occurs in __________

•7 major pandemics since 1817
–2001- 184,000 cases; 2728 deaths; 94% were in Africa
–1961- 5 million cases; 250,000 deaths
- (-) curved rods

- developing parts of world
•Epidemics in areas with ______


•_________ in some countries

•Sporadic outbreaks along ___________

Pathogenesis
•Requires large __________
-little or no sewage treatment

-Endemic

-US Gulf Coast due to raw shell fish

-inoculum (10^8-10^10 cells) due to stomache acid
•Vibrio attaches to ___ in ____ then _____

•Causes severe diarrhea (“rice water” up to 20 liters per day) which can result in _____

•If untreated, mortality rate of _____

•Treatment- electrolyte replacement therapy

–Reduces mortality rate to _____
-epithelical cells, in small intestine, then releases enterotoxin

-death from dehydration

-25 to 50%

-1%
Salmonella typhi- typhoid fever

•Gram negative __________

•Causes __________; mainly transmitted by ______

•Less than _____ cases per year in US
-bacillus; can colonize intestine

-gastroenteritis, contaminated water

-400
Legionella pneumophila- Legionellosis

•Gram _______

•Transmitted in _______

•First recognized after outbreak at American Legion meeting in 1976

•Commonly found in __________

•Symptoms can be: none, sore throat, cough, headache, fever or pneumonia.

–Mild symptoms are called _______

–More serious pneumonia type symptoms called ________
-negative bacillus

-aerosols

-cooling towers of air conditioning systems; also in hot tubs

-Pontiac fever

-Legionellosis
•The following organisms are very resistant to chlorine and UV radiation so sedimentation and filtration
methods must be used to prevent these _________

•Giardia intestinalis
– Giardiasis
•Cryptosporidium parvum
–Cryptosporidiosis
•Entamoeba histolytica
–Amoebic dysentery
-pathogenic protozoans from entering the water supply
Giardia intestinalis- Giardiasis

•Flagellated ________

•Causes ?

•Some people can be _________

•Can come from ______

•Is found in __________
-protozoan; produces tough cysts

-carriers (no symptoms)

-drinking water, ingesting swimming pool water, lake water, stream water

-97% of surface waters in US
Cryptosporidium parvum- Cryptosporidiosis

•Produces _________

•Caused ____________ in US (Wisconsin, 1993).

•Over 400,000 people were infected from ___________

•Causes _____________

•Common in ___________
-thick walled oocysts

-largest single outbreak of waterborne disease

-municipal water supply

-mild gastrointestinal illness

-cattle & other warm blooded animals
Entamoeba histolytica-Amoebic dysentery

•Anaerobic; produces ____

•Symptoms can be ?

•If intestinal wall is _____

–Intestinal ______

–Untreated- can ____________

•100,000 ________________
-produces cysts

-invaded, this condition is dysentery

-inflammation, fever, blood & mucus in stool

-invade liver, lung, brain

-deaths per year worldwide, several hundred per year in US
•Pathogens- microbes that_____

•Pathogenicity- ability of a _______

•Opportunistic pathogen- microbe that causes ___________

•Infection- a microbe is _______
-cause disease

-pathogen to cause disease

-disease when host defense is absent or compromised
•Disease- a microbe causes ________

•Infection precedes disease.

•Infection often begins at________________ found throughout the body.
-damage or injury to host that impairs host function
Normal Human Flora

•There are _________________

Sites where bacteria are normally found:
•Skin
•Oral cavity
•Gastrointestinal tract
•Respiratory tract
•Urogenital tract
-billions of microbial cells living in and on the human body
Normal flora of the skin

•Microbes grow mostly in _________

•Associated with ___________

•Factors that affect types of normal flora- _________
-moist areas- underarms, genitals, etc

-sebaceous (oil) glands & apocrine (sweat) glands (pH 4-6)

-weather, age, personal hygiene
Bacterial species commonly associated with the skin:

•Most are_______

•Staphylococcus

•Gram _____

•Propionibacterium

•Gram _____

•Propionibacterium acnes can cause _____
-Gram +

-Gram +, aerobic cocci

- +, anaerobic rods

-can cause acne
•Acinetobacter

•Gram _____

•Few G ________
- (-) rods

- (-) bacteris found on skin
Normal flora of the oral cavity

•Bacteria in the mouth prior to tooth formation are mainly ______________

•Acidic glycoproteins in saliva form a layer on teeth providing a firm __________, usually ___ species

•Extensive growth of these microbes results in ________

•microflora of dental plaques make ____ taht decalcify tooth enamel; results in ______-
-aerotolerant anaerobeds such as streptococcus & Lactobacillus

-attachment site for microbes, Streptococcus

-thick bacterial layers called dental plaque

-acids, dental caries (tooth decay, cavities)
•Tooth surfaces in and near the gingival crevice where food particles remain are common sites of tooth decay. Floss!!!

•Diets high in ______

•Lactic acid bacteria _______

•Streptococcus mutans produces_____________ (polysaccharide used for attachment to tooth surface) only when sucrose is present

•Diets containing fluoride during formation of ______________

•Incorporation of fluoride into the calcium phosphate crystal matrix increases resistance to decalcification.
-sucrose are cariogenic- cavity causing

-ferment the sucrose to lactic acid

-dextran

-tooth enamel make teeth more resistant to tooth decay
Normal flora of the gastrointestinal tract

The stomach:

•pH ____

•Only ____ tolerant bacteria can colonize stomache wall- ex. ________

•Very few bacteria are found in stomach fluids
- 2

-acid, Helicobacter pylori (pepti ulcers)
The small intestine:

•# of bacteria _________

•Duodenum: few bacteria due to _________; mainly ______

•Jejunum: Enterococcus, Lactobacillus

•Ileum: microbiota reflects that of large intestine; large number of ______ & _____ like _____
-increases down through small intestine (due to rising pH)

-stomach acids; Gram + cocci and bacilli

-Bacteroides & facultative aerobes, E. coli
The large intestine:

•Fermentation vessel; ________, mostly _____

•Commonly _________

•Small number of facultative aerobes (E. coli); consume oxygen which allows obligate anaerobes to grow
-many bacterial (>300 species), mostly anaerobes

- 10" bacterial cells/gram of intestinal contents
•Diet affects intestinal flora- ex.

•Some vitamins are produced in intestine by bacteria-

•Antibiotics can reduce number of normal intestinal flora, can lead to digestive problems
-more meat in diet, more Bacteroids

- Vit B12, K, riboflavin, thiamine
Common anaerobic intestinal flora:
•Bacteroides
•Clostridium
•Enterococcus

•Many adults also have methanogens which convert ____________________

•Bacteria in the intestinal tract are constantly being displaced downward by the flow of material & ____________

•The growth rate of bacteria in the lumen of the intestinal tract is ____________
-hydrogen & carbon dioxide to methane gas

-replaced by new microbes

- 1-2 doublings per day
Normal flora of the respiratory tract

Upper respiratory tract-

•Most bacteria that are breathed in are

•Are many
- nasopharynx, oral cavity, & throat

-trapped in mucus

-opportunistic pathogens in nasopharynx
Opportunistic pathogens which can be found in the nasopharynx:

•Staphylococcus aureus

•Causes ________

•Streptococcus pneumonia

•Causes ________
-sinus & ear infections

-sinus infections & bronchitis
•Streptococcus pyogenes

•Causes _________

•Corynebacterium diphtheriae

•Cause ________
-sinus infections & "strep" throat

-diphtheria
Lower respiratory tract-

•Bacteria are _______

•Lower respiratory tract is lined with _____ to _________ where they are caught in ___ &____
-not normally found in lower respiratory tract

-cilia, push bacteria & dust particles up, caught in mucus & saliva
Normal flora of urogenital tract

•Bladder is _______

•Several types of ___ are associated with urethra

•Escherichia
•Klebsiella
•Proteus
•Neisseria (____)

•Many of these are ______

•Lactobacillus acidophilus is often found in ______
-normally free of bacteria

-faculatative anaerobes (mostly Gram (-) rods)

-Gram (-) cocci

-opportunistic pathogens

-often found in vagina of adult women
Virulence Factors
•Structures & characteristics of _____ that allow them to ____

Adhesion- ability to ______

Virulence factors affecting adhesion:

•Capsule-outer _______, helps bacteria in ______

•Fimbriae- necessary for some organisms to attach. (_____)
-pathogens, cause disease

-adhere to mucus membranes

-polysaccharide layer, attachment

-(Neisseria & E.coli)
Invasion & Colonization
Invasion:
•Pathogens must be able to ________

•They can reach ______ through ___ or ____
-penetrate the outer layer of skin cells (epithelium)

-inner layers of skin cells, through lesions or mucus membranes
Colonization:
•Once it has invaded a host, it can establish itself and grow

Examples of virulence factors affecting invasion & growth

•The O & Vi _______

•O – ______. prevents ____

•Vi – _____. prevents ____ & _____

•Siderophores:
-Compounds that ___ & make it available to the bacterial cell

•Leukosidin:
-Staphylococcus aureus produces this compound which ______, decreasing _____
-antigens of Salmonella

-cell surface polysaccharide, prevents phagocytosis

-capsule antigen, prevents complement binding & antibody mediated killing

-bind iron

-lyses white blooc cells, decreasing host resistance
Localized infection - Organisms ______

Systemic infection - Organisms _______
-grow locally at site of invasion

-spread through body using blood or lymphatic systems
Dissemination of the pathogen:
•Many pathogens make virulence factors which help them __________

•Many of these are _____ which break down ___
-spread from the initial infection site

-enzymes, tissues
Examples of virulence factors which break down tissues:
•Hyaluronidase-

•Destroys ____ that holds ___ together

•Produced by _____&_____

•Collagenase-

•Breaks down ______

•Produced by _____
-polysaccharide that holds animal cells together

-staphyloccus & streptococcus

-down collagen

-Clostridium
•Streptokinase-

•Breaks down _____

•Clots are made by____j to wall off ___ & prevent their spread to _____

•Made by ________

•Hemolysins- ______ of animal cells- lyse _____

•Disrupt
-fibrin clots

-host, bacterial infections, healthy tissues

-Streptococcus pyogenes

-cytoplasmic membrane, lyse red blood cells
Toxins:
•Compounds produced by pathogens that ______

3 major groups of toxins:
•Exotoxins
•Enterotoxins
•Endotoxins
-damage tissues far from infection site
Exotoxins
•Proteins secreted by bacteria that can _________

Examples of exotoxins:
Diphtheria toxin

•Inhibits ____

•Produced by Corynebacterium diphtheriae (causes ____)

•Toxin is produced by bacteria that are ____ which carries ____

Tetanus toxin

•Acts on _____;causes _____; can lead to ____

•Produced by Clostridium tetani which infects ____

Botulinum toxin

•Prevents _______-results in ____ or ____

•Produced by Clostridium botulinum

•Organism grows in _______, where it produces ____

•Botulism is caused by ____, not by ______
-damage tissues far from infection site

-protein synthesis

-diphtheria

-lysogenized by phage B(beta), tox genes

-motor neurons, continual contraction of muscles, lockjaw

-deep wounds

-muscle contraction, respiratory or cardiac failure

-improperly stored foods, toxin

-ingesting toxin, not infection with C. botulinum
Enterotoxins

•Proteins that act on ____, cause ____

•Produced by _________ such as Clostridium, E. coli, Salmonella

•Cholera toxin

•Produced by _______

•Causes secretion of ___________
-small intestine, cause diarrhea

-food poisoning organisms

-Vibrio cholera

-massive amount of water into small intestine (diarrhea)-death by dehydration
Endotoxins

•When ______ lyse, ____ portion of LPS is released

•LPS from many organisms, such as E. coli, Salmonella, Shigella, is toxic

•Cause ____,___,___- rarely fatal
-Gram (-) bacteria, lipid A

-diarrhea, fever, vomiting
Nonspecific Host Defenses:

Anatomical defenses:

1. Skin
-______
-______
2. Mucus
-_______
3. Enzymes
-______
-Physical barrier
-Dry, low pH

-Traps bacteria

-Lysozyme in tears
Inflammation

•Redness, ________

•Histamine _____

•Capillaries ____:Fluids containing ___ leak into wound

•Clot forms to ______

•Septic shock- ____&___ spread through body
-swelling, pain, heat

-released

-to dilate, WBC's

-localize pathogen

-infection and inflammation
Fever:

•Some products of ______ are ____

•Endogenous ______ are produced by _____

•Higher temp:

–Increases ______

–Slows _________

–However, very high temp damages host tissue
-pathogens (endotoxin) are pyrogenic (fever-inducing)

-pyogens, leukocytes

-phagocytosis & antibody production

-bacterial growth
The host's ability to resist infection depends on:

•Age – _________ more susceptible

•Stress –____________ increases susceptibility

•Diet –_______________ increases susceptibility

•General health and lifestyle –____________ increase susceptibility

•Prior or concurrent disease- increases susceptibility

•Many hospital patients with ________(ex.cancer or heart disease) acquire nosocomial infections because they are _____

•Genetic conditions especially those affecting immune system
-young & old

-high stress

-low protein & calories

-smoing, excess alcohol consumption, drug use, & lack of sleep

-noninfectious diseases

-compromised hosts