In Latin "virus" means
poisonous malodorous substance
Who was the first person believed to have died from a virus
Pharaoh Ramses V
When were the first plant and animal viruses discovered?
1890s
What did Pharaoh Ramses V die from (potentially)?
small pox
What is the Genome of a Virus?
either DNA or RNA
Give the 5 basic characteristics of Viruses
1. genome of either RNA or DNA
2. Obligate intracellular parasites
3. Composed of nucleic acid and proteins
4. Filterable
5. Not susceptible to antibiotics
2. Obligate intracellular parasites
3. Composed of nucleic acid and proteins
4. Filterable
5. Not susceptible to antibiotics
What does filterable mean?
direct indication of size
what are the 2 generic classes of viruses?
naked viruses and enveloped viruses
Describe a nucleocapsid
nucleic acid-protein assembly packaged within the virion
What is the capsid composed of?
capsomeres
what makes up capsomeres?
protein subunits
what are the 3 types of nulceocapsid symmetry?
icosahedral, helical, complex
Describe the core
located within the nucleocapsid. Made of nucleic acid and protein.
what does icosahedral mean?
20 sided
what is the usual protein found in the core?
transcriptase
Describe an enveloped virus
nucleocapsid surrounded by an altered host cell membrane
What does the envelope of a virus contain?
viral-encoded proteins such as peplomers or spikes
what is the purpose of spikes?
essential in host cell - virus interaction
List the 7 basic steps of replication
1. Adsorption
2. Penetration
3. Uncoating.
4. Replication of proteins
5. Replication of nucleic acids
6. Maturation.
7. Release
2. Penetration
3. Uncoating.
4. Replication of proteins
5. Replication of nucleic acids
6. Maturation.
7. Release
What are the 2 types of release at the end of replication?
cytolysis and budding
where is the Eclipse phase?
Between steps 4 and 5 of replication
What is it called when an individual is infected but you cannot see s/s of disease yet?
Eclipse phase
How does adhesion work?
attachment of virus to host cell via receptors like the primary receptor and the co-receptor
How does penetration work?
receptor-mediated endocytosis
Describe plaque formation
produced viral colonies. In the middle of the plaque is the virus
How are viruses classified?
the Baltimore classification
Class 1 virus
dsDNA. Ex: herpes simplex virus, -pox viruses
Class II virus
ssDNA ex: parvovirus affects dogs
Class III virus
dsRNA ex: rotovirus
Class IV virus
+ssRNA ex: polio
Class V virus
-ssRNA ex: mumps, measles, influenza
Class VI virus
+ssRNA ex: retroviruses, HIV
Class VII virus
partially dsDNA with RNA intermediates ex: Hep B
what is the difference between class IV and class VI viruses?
Class 6 has reverse transcriptase in it
what does the + mean?
the genome of the virus can be directly used as mRNA
What does the - mean?
the genome of the virus cannot directly act as mRNA
Where does replication generally take place in DNA?
the nucleus
what are the 2 rounds of transcription in DNA viruses?
one from parental DNA and one from progeny DNA
what's in the nucleus that viruses need?
nucleotides, polymerases
what is the purpose of EVP?
help in replication
what is the purpose of LVP?
act as structural proteins
what are examples of structural proteins?
capsid, peplomeres
where is polymerase typically found?
in the nucleus
Where does replication of RNA in viruses usually take place?
cell cytoplasm
why can replication of RNA take place in the cell cytoplasm?
The RNA viruses carry their own polymerases
what factors determine viral pathogenesis?
cell susceptibility, tissue tropism, immune resistance factors
What do receptors determine?
the presence of receptors determine whether a virus will infect your lungs or kidneys or liver etc.
what are immune resistance factors?
interferons, acquired immunity
what are the two different types of acquired immunity?
humoral immunity, cell-mediated immunity
what cells are in charge of humoral and cell-mediated immunity?
B cells- humoral
T cells- cell-mediated
T cells- cell-mediated
Define Interferons
Inducible cellular proteins
what are the 3 common types of interferons
alpha, beta, and gamma
which interferons function in viral immunity?
alpha and beta
which interferon/s function in the inflammatory response?
gamma
what do alpha and beta interferons do?
induce synthesis of antiviral proteins
is anti-viral activity specific or non-specific?
non-specific
what happens in a person is interferon deficient?
they will develop a lot of viral infections
what happens when a cell become virally infected?
the cell then expresses viral antigens and is considered "foreign".
what are examples of cytotoxic cells?
cytotoxic T cells, Natural Killer cells
What do cytoxic cells do?
release perforine and granzyme B
what do perforines and granzyme B do?
leads to target cell death through apoptosis
What is the major part of Humoral Immunity?
Antibodies
what do antibodies do?
bind to free virions and "neutralize them"
example of acute viral infection:
common cold
example of persistent infection with shedding
hepatitis
example of latent viral infection:
herpes
example of persistent slow following acute infection:
HIV
example of persistent slow infection:
prion diseases
what are the 3 types of antigenic variation?
mutation, recombination, gene switching
what is another name for mutation?
antigenic drift
what is another name for recombination?
antigenic shift
what causes mutation?
change in nucleic acid sequence
what does mutation lead to?
subtle changes in antigen expression
give examples of antigenic drifts:
influenza virus, HIV
why are RNA viruses more susceptible to mutation?
they lack proofreading
what happens when a virus changes?
antigen changes, surface proteins change, change in susceptibility to drugs
how common is antigenic drift?
very common
what causes recombination?
dual infection by multiple strains of virus
what is the result of recombination
substantial variation in antigen expression
how common is antigenic shift?
not very
how many types of influenza are there?
3. A, B, C,
how are strains of influenza determined?
by their H and N spikes
what are pandemics of influenza associated with?
zoonotic transmission
what does H stand for?
hemagglutinin
what does N stand for?
Neuraminidase
what does hemagglutinin do?
attaches to host cells
what does neuraminidase do?
involved in viral budding from host cells
what is unique about influenza?
it has the amazing ability to shift from antigenic drift to shift
what does an antigen drift of influenza cause?
epidemics, that's why there must be a new vaccine every year
what does an antigen shift of influenza cause?
pandemics, usually prolonged
how are influenza strains named? ex: A/Fujian/411/2002 (H3N2)
virus type, geographic origin, strain number, year of isolation, virus subtype
T/F Influenza is the leading cause of U.S. vaccine preventable deaths?
True
what is zoonotic mean?
animal acquired?
when was the Spanish flu outbreak?
1918
describe gene swithching
causes relapsing fever, genes from different infections are switched over
what is an organism that exhibits gene switching?
borrelia recurrentis
list the 6 cytopathic effects of gene switching?
1. inclusion bodies
2. cell lysis
3. cell rounding
4. syncytia formation
5. apoptosis
6. transformation
2. cell lysis
3. cell rounding
4. syncytia formation
5. apoptosis
6. transformation
what are inclusion bodies?
remnants of viral proteins within host cells
what is syncytia formation?
multinucleated giant cell that comes when cells fuse together
what is apoptosis
programmed cell death
what is caused by apoptosis?
DNA fragmentation, formation of cellular "blebs", no inflammation
define transformation
the change of normal cells to cells exhibiting the properties typical of tumor cells
approximately ___% of all cancers are due to viruses
10-15
what 4 changes happen in transformation
morphology, behavior, biochemistry, growth patters.
what change in morphology happens during transformation
flat cells change to round cells
what change in behavior happens during transformation
contact inhibition- cells touch and stop growing
what change in growth patterns happen during transformation
cells are pushed through checkpoints in cell cycle so they keep growing regardless of mutations
Who discovered oncogenes
Payton Rous
what are the 2 types of oncogenes?
v-onc and c-onc
what is another name for c-oncogenes?
proto-oncogenes
describe c-oncogenes
cellular genes that promote cell cycle regulation
describe v-oncogenes
c-onc genes picked up by viruses
oncogenes alter what?
typical cell cycle regulation
what happens in the 5 stages of the cell cycle?
G1: growth phase, RNA and Protein synthesis
G0: resting stage
S: DNA replication
G2: RNA and Protein synthesis
M: Mitosis
G0: resting stage
S: DNA replication
G2: RNA and Protein synthesis
M: Mitosis
how is the cell cycle controlled?
through checkpoints that regulate the progression of cell from one stage to another
what are the 5 normal functions of oncogenes?
growth factors
growth factor receptors
signal proteins
cell cycle and cell death regulators
transcription factors
growth factor receptors
signal proteins
cell cycle and cell death regulators
transcription factors
what are 2 tumor suppressors?
p53 and RB
what are 2 growth activators:
hormones and protoncogenes
when does virus-induced transformation occur?
tumor suppressors are inactivated
enhancement of growth factors
enhancement of growth factors
how are growth activators enhanced?
viral oncogenes are incorporated into the host genome.
viral DNA is incorporated near a proto-oncogene
viral DNA is incorporated near a proto-oncogene
what are 3 transforming viruses?
papillomavirus
Human herpes
Hep B
Human herpes
Hep B
what are the 4 types of retroviruses?
HTLV-1
HTLV-2
HIV1
HIV2
HTLV-2
HIV1
HIV2
what does HTLV stand for?
human T-cell lymphotrophic virus
what are HTLV 1 and 2 and HIV 1 and 2 subdivided into?
oncoviruses and lentiviruses
what is a lentivirus?
slow growing virus
is HIV 1 or 2 more common?
1
what is the structure and class of retroviruses?
enveloped +ssRNA virus. Class VI
what is essential in recognition of target cells?
envelope glycoproteins
describe the order of the retroviral gene structure?
LTR-GAG-POL-ENV-LTR
what is LTR
long terminal repeats
what is GAG made of?
nucleoid capsid, core,
what is POL made of?
RT, RNase H, Integrase
what do ENV do?
envelope proteins code for spikes
what are the 9 steps of HIV replication?
1. adsorption
2. penetration and uptake via gp41
3. Reverse transcription in cytoplasm
4. DNA replication
5. Move into nucleus for integration into host chromosomes as provirus
6. Host transcription factors bind LTR. Cytokine secretion by immune cells can enhance HIV transcription
7. Assembly
8. Budding of immature viral particle
9. Long proteins are cleaved by viral proteases now making the virus infectious
2. penetration and uptake via gp41
3. Reverse transcription in cytoplasm
4. DNA replication
5. Move into nucleus for integration into host chromosomes as provirus
6. Host transcription factors bind LTR. Cytokine secretion by immune cells can enhance HIV transcription
7. Assembly
8. Budding of immature viral particle
9. Long proteins are cleaved by viral proteases now making the virus infectious
Why does HIV mutate so quickly?
lack of proofreading activity in RT
what is HAART?
highly active anti-retroviral therapy
what is the first stage of HIV?
4-8 weeks initial infection
what is the second stage of HIV?
2-10 years asymptomatic phase
what is the third stage of HIV?
2-3 years AIDS/ARC
Define AIDS
immunosuppresion caused by HIV due to drop in TH cells to levels of <200
Where does HIV reside?
lymph nodes
what are the 3 causes of immunodeficiency by HIV?
apoptosis
impaired lymphopoisis
altered cytokine/chemokine secretion
impaired lymphopoisis
altered cytokine/chemokine secretion
CD4 cells susceptible to HIV are found in what 5 places:
bowel epithelium
renal epithelium
brain microglia
follicular dendritic cells
fetal astrocytes
renal epithelium
brain microglia
follicular dendritic cells
fetal astrocytes
what 4 common diseases are associated with HIV infections?
pneumocystis carinii
kaposis sarcoma
mycobacterium species
cryptosporidium sp
kaposis sarcoma
mycobacterium species
cryptosporidium sp
what does pneumocystis carinii cause?
atypical pneumonia
what does mycobacterium sp. cause?
TB
what is cryptosporidium sp.?
parasite that causes diarrhea
where did HIV originate?
Congo region of Africa
what did HIV originate from?
SIV simian immunodeficiency virus
where was SIM found?
chimpanzees
define antibiotics
antimicrobial agent produced by a bacteria or fungus
antimicrobial agent produced in the lab
synthetics
antimicrobial agent produced by a bacteria or fungus but altered in the laboratory
semi-synthetic
an antibiotic that kills or inhibits a wide range of microbes would be:
broad spectrum
an antibiotic that kills or inhibits a limited range of microbes
narrow spectrum
what is an example of a broad spectrum antibiotic:
tetracycline
what is an example of a narrow spectrum antibiotic:
penicillin
what does -cidal mean?
to kill
what does static mean?
to inhibit
what are characteristics of an ideal antimicrobic:
selectively toxic
soluble and active in dilute concentrations
stable
not susceptible to antimicrobial defenses
complements host defenses
does not compromise the host
soluble and active in dilute concentrations
stable
not susceptible to antimicrobial defenses
complements host defenses
does not compromise the host
what do beta lactams do?
bind to penicillin-binding proteins that cross link NAM
what are 3 examples of beta lactams
penicillins
cephalosporins
carbapenems
cephalosporins
carbapenems
what is vancomycin
fairly toxic antibiotic. last resort
what is bacitracin
only given topically
what is PBP?
penicliin binding protein
what is penicillin derived from?
fungus penicillin sp
what is the natural form of penicillin?
penicillin G
what is penicillin made up of?
thiozolidine ring, beta lactam ring, variable side chain
are penicillins more effective against gram + or gram - bct?
gram +
how is resistance acquired
via production of beta-lactamase
what does beta-lactamase target?
the beta-lactam ring
what is the structure of cephalosporins similar to?
penicillin
define intrinsic resistance
due to natural anatomical or physiological barriers
define acquired resistance
due to the acquisition of antibiotic resistance
what are SUPERBUGS?
strains of pathogens that have become increasingly antibiotic resistant
what is MRSA?
methicillin resistant staphylococcus aureus
what is VRE
vancomycin-resistant enterococus
what is CRE?
carbapenem-resistant enterobacteriaceae
what is C diff and how do you get it?
clostridium difficile, get it by overuse of antibiotics. causes psudomembranous colitis
what are side effects of host/drug reactions
toxicity ( renal/hepatic) allergic responses, alteration of microflora
what is an example of an alteration of microflora?
yeast infection
what is the function of normal microbiota?
modification of pH and oxygen tension
chemical excretion
creating physical obstacles
stimulating immune system
chemical excretion
creating physical obstacles
stimulating immune system
what is the source of most opportunistic infections?
normal microbiota
where are sources of normal microbiota?
skin, alimentary tract, respiratory tract, genitourinary tract
what are microbe-free body sites that should be sterile?
muscles, nervous system, blood, some internal organs
what factors promote disease?
adherence factors such as capsules and fimbriae, extracelllar enzymes, bacterial toxins, intracellular survival, infectious dose
what is an exotoxin?
protein released from the cell, no fever and is destroyed by heat
what is an endotoxin?
LPS, within cell envelope, heat stable, fever, ssytemic
what causes strep throat
streptococcus pyogenes
what causes fever?
release of IL-1 from macrophages,
what does IL-1 do?
acts as an endogenous pyrogen induces the release of prostaglandins
what do prostaglandins do?
reset the body temperature causing fever
what inhibits prostaglandins?
NSAIDS and ASA
what are the 3 general types of exotoxins?
cytotoxins
neurotoxins
enterotoxins
neurotoxins
enterotoxins
why are intracellular organisms harder to kill?
they can evade immune response by growing inside organisms
what is an infectious dose?
how much you have to ingest to become infected
what is a reservoir
any site where infectious organisms reside
what are carriers?
human reservoir. healthy looking individuals who are reservoirs of infection
what are the types of carriers
asymptomatic, incubation, chronic carrier, passive carrier
what is an example of an asymptomatic carrier?
someone with E. coli in their gut
what is an example for incubation?
HIV
what is an example of a chronic carrier?
organisms resides permanently and is shed through fecal matter
what is an example of a passive carrier?
picks up organism and then transfers to another without knowing. classic example is a dr. or ns
who is an example of a famous chronic carrier?
marry mallon "typhoid mary"
define a vector
agents that transmit disease
what is a biological vector?
involved in the life cycle of the pathogen, for example mosquito, tick flea
what is a mechanical vector?
involved in the physical transmission of the pathogen. example flies and roaches
what are 3 examples of direct transmission?
droplet nuclei
oral-fecal route
venereal spread
oral-fecal route
venereal spread
what are examples of indirect transmission?
fomite, droplet nuclei, oral-fecal route
what is a fomite?
any inanimate object that can harbor infections. example: needles, door handles
what is a nosocomial infection?
hospital-acquired infection
what is the problem with nosocomial infections
typically more virulent, more drug resistant