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exam 4
virology
196
Microbiology
Undergraduate 3
04/08/2015

Additional Microbiology Flashcards

 


 

Cards

Term
name of professor who runs virology blog
Definition
racaniello
Term
viruses
Definition

organic nanoparticles

lean, mean machines

genetic info w/ a couple proteins in order to func

hijack the host cell machinery

virus mimicry uses combos of genetic engineering and chem modification

Term
virus particle size
Definition

around 100 namometers

like holding an orange in a circus tent (mammalian cell)

Term
virus classification
Definition

host cell: animal, plant, fungal, bacteriophage

Shape of capsid: helix or icosahedron

virus struc:  prescence or absence or envelope (phospholipid bilayer of host cell)

type of nucleic acid: DNA viruses (double stranded and less common than single)

RNA viruses (pos sense single stranded reverse transcribing DNA and less common double stranded)

reverse transcribing (double stranded reverse transcribing DNA, and single stranded reverse transcribing RNA)

Term
Baltimore classification
Definition
codes the many different ways virus can get from genome to protein
Term
virus structure simplified
Definition

viral nucleic acid (all viruses have this)-single stranded, double stranded DNA or RNA, linear or circular

protein coat (all viruses have this)

envelope-not all viruses have this protective phospholipid bilayer

Term
protein coat/capsid
Definition
main func to protect nucleic acid from the enviro (1 or more repeating units, virus can't carry a lot of info), capsid is made up of repeating units which are proteins synthesized by the viral nucleic acids
Term
what is a virus
Definition

nucleic acid-RNA or DNA, single or double strands, circ or linera

protein coat (capsid)-helical or iscosahedral, subunit construction

envelope-present or not

Term
diversity of structure
Definition
can be very diverse in structure shape and size
Term
three advantages of virion structures
Definition

1. protenction-protect the fragile nucleic acid genome from physical, chem, or enzymatic damage

2. specificity-recog and first interac w/ host cell

3. delivery of genome into the cell

Term
virus capsid struc
Definition

protein subunit construc based upon hydrophobic and electrostatic interactions

make up the two basic struc or iscoasahedral (hexagon like shape) or helical

Term
4 steps viral life cycle
Definition

1. virus partical attracted to host cell, specific or general

2. delivery of genome

3.takes over machinery of host cell

4. more particles form and virus can go infect others

Term
toll of virusal diseases
Definition

have endemics and outbreaks

worldwide problems

can get better with vaccines

Term
what is an antibody (and the 2 we need to know)
Definition

large protein produced by immune system to identify and neutralize foreign objects

IgG-majority of antibody response, monomer

IgM-early stages of antibody response, pentamer

Term
general sx of any hep infection
Definition
yellow tint to eyes and skin, inflammed stomach, espophogas liver stomach spleen pancrease, edema in legs, numbness, tingling
Term
hep a virus
Definition

wide spread subclinical infections

enteral-fecal/oral route enteral

acute only-no carrier or chronic condtion

prejaundice phase lasts weeks to months, abrupt onset of fever, nauseas, vomiting, anoerxia

jaundice phase-lasts 1-2 weeks, dark urine (melanine) and or jaundice (yellow skin due to bile in skin)

immune respone w/ IgM detected first, and IgG detected for life

dx is raised Igm and igg anti HAV antibodies (6 weeks to several months)

elevated liver enzymes (especially ALT-alanine transaminase enzyme)

Term
clinical picture HAV infection
Definition

can be excreted in feces before even clinical illness develops

IgM detected first

IgG for life

ALT levels elevated

Term
HAV tx and prevention
Definition

treatment-non speicifc tx, rest and avoid alcohol and toxic substance, most people recover w/in 3 months, nearly all px recover w/in 6 months

prevention-passive immunization w/ human gabba globuin or active immunization w/ inactivated hep A vaccine

Term
Hep B virus
Definition

major cause of chornic hep, cirrhoissi and primary hepatocellular carcinoma

transmission by bloodborne, infectious blood or body fluids (semen, vaginal fluids) also perinatal infection, cannot be spread by kissing, hugging, or breastfeeding

clinical sx-loss of appetite, fatigue, fever (low grade), muscle and joint aches, nausea and vomiting, yellow skin an dark urine due to jaundice

immune response-IgG antibodies for life

dx-liver func tests: ALT enzyme levels in blood

Term
viral hep B (misc)
Definition

about a third of world's pop has been infected w/ HBV at some time in their lives

replicate through an RNA intermediate by activity of reverse transcriptase which relates them to retroviruses like HIV

HBV genome is a partially dsDNA molecule and has a viron assoc DNA polymerase

350 mill chronic carriers

Term
clincial pic HBV (3 types infection)
Definition
acute, asymptomatic, chronic
Term
asymptomatic infection
Definition

majority of infections are asymp, HBsAg in serum for short time (1-2 months)

antibodies against HBsAg persist for life providing lifelong immunity

Term
acute HBV infection
Definition

long incubation period

sx as in acute hep a

hbsag in serum for less than 6 months (transient)

majority of px recover

antibodies against hbsag persist for lifelong immunity

hbv+ hdv=fulminant hep

Term
chronic hbv
Definition

one of the common long term results of acute hep b is calles persistant viral hep

hbsag in serum persists for greater than 6 months, probably life

Term
hbv tx
Definition

interferon alpha-decreases the stability of the viral genetic material, casues side effects including fever, fatigue, muscle aches, depression

nucleoside/nucleotide analongs inhibit reverse transcriptase have been developed (originally for HIV tx)

still work to do to determine optimal tx's

Term
HBV prevention
Definition

passive immunity-hep b immune globulin, standarf immune serum globulin

active immunity-immunizations

Term
hep c
Definition

transmitted Iv drug use, post transfusion, tattoos, manicure equip

clinical sx-abdominal pain (right upper abdomen), abdominal swelling (ascities), clay colored or pale stools, dark urine, fatigue, fever, itching, jaunice, loss of appetite, nausea, vomitting

immune response-igg antibodies for life

dx-blood tests (EIA enzyme), liver func test, genetic testing (six genotypes exit and have to test-most americans have type 1), liver biopsy can determine exent of damage

Term
clincial picture of Hep c
Definition

most infections are insidious (slow)

time to clinical hep greater than 10 years

time to cirrohis and cancer a couple decades

 

Term
hcv treatment and prevention
Definition
combo of antiviral ribavirin for 24-48 weeks depending on HCV genotype, most effective 1st 6 months after infection as opposed to chronicity
Term
hep d
Definition

transmission by bloodborne, sexual, needle sharing, infected blood products

clinc sx-more severe than others-abdonimal pain and swelling, loss of appetite, sore throat, joint and muscle pain, clay colored and pale stools, dark urine, fatigue, faver, itching, jaundice, loss of appetite, nausea, vomiting,

immune response-anti HD antiboidies do not always persist after acutre infection is cleared

dx-blood tests (anti delta antibodies, serum HDV RNA)

Term
hep d tx
Definition

no effective antiviral tx

hyperimmune d globulin avail for pre or post exposure prophylaxis

progression to cirrohis usually takes 5 to 10 years but can appear after 2

high proportion of px get cirrohis and die of hepatic failure

liver transplants may be considered

mortality is 10x higher than hbv

Term
hdv prevention
Definition

key is that it is a sattelite virus and requires hbv infection first

defective RNA virus on its own

uses the hbsag antigen as its own viron coat

hbv vacc prevents against hdv based on this principle

Term
hep e
Definition

transmission-fecal/oral, enteral, principally due to contaminated water

clinc sx-jaunice, anoerxia, hepatomegaly, abdominal pain and tenderness, nausea and vomitting, fever

immune response-noncytopathic (doesn't kill cells) but suspected to cause immune mediated liver damage through cytotoxic t cells

dx-speficic antibodies in blood, often epidemic outbreaks occur

Term
HEV prevention and treatment
Definition

treatment-none avail usually self limiting, hospitilzation required for px w/ fulminant dx

prevention-maintain safe public water sanitation, proper disposal of waste

Term
central dogma molecular biology
Definition

DNa is the start (orginal design of a machine from a factory)

made into RNA (blueprints of the machine)
made into proteins (machines of a cell)

DNA can be made into DNA  (DNA polymerase)

RNA can be made into RNA (RNA polymerase)

RNA can be made back into DNA by reverse trascripterase

Term
retrovirus
Definition
virus that undergoes reverse transcription of RNA into DNA during the viral lifecycle (HIV)
Term
endogenous retroviruses
Definition

HIV retrovirus integrates into the host cell genome

ancient retroviruses inserted bits of DNA into the primate genome millions of years ago

8 percent human genetic code consists of ERV's

researchers propose that insertion of DNA by ancient retroviruses helped genes like p53 become master gene regulators that can switch on and off many genes

Term
this week in virology article
Definition

protein called syncytin, a membrane fusion protein, is essential in formation of the placenta and the gene is from an ERV

ERV are necessary for the way humans are today

Term
HIV/aids
Definition

HIV is an RNA virus w/ 2 identical strands (but not double stranded) of RNA as the genome

HIV replicates in cells of the human immune system

HIV has been assoc w/ syndrome called AIDS

AIDS px develop anti HIV antibodies (key to testing for HIV infection

Term
2 human speicies of HIV
Definition

HIV1-high virulence, global prevalence, from common chimpanzee

HIV2-lower virulence, low infectivity, prevalence in west africa, origin from sooty mangabey

HIV 2 more closely related to SIV than it is to HIV 1

Term

lab dx HIV

 

Definition

can be from an ELISA (enzyme linked immosorbent assay, uses antibodies to change color)

western blot-anitbodies bind to proteins and change band color, like a pregnancy test, need 5 to show up for pos

oraquick-now in home, not as accurate, about 20 min

uni gold recombigen-plasma, serum, whole blood, must be performed by med professional, all rapid tests need western blot follow up

Term

hiv pathogenesis stage 1

 

Definition

acute or primary HIV dx stage

acute retroviral syndrome

develops 2-8 weeks after exposure and lasts 2-4 weeks

charac by mono like illness with fever, sweat, lethargy, headache, diareha,

high levels of virus are produced and spread throughout body

no notable immune repsonse detectable

period is called window of infectivity before seroconversion

**transmission can occur

Term
hiv stage 2
Definition

asymptomatic HIV disease stagelasts for 6 months to 10+ years

HIV in blood drops to a low level and antibiodoies against HIV produced

indiv appear healthy

dsDNA migrates to nuclease and integrates w/in the host chormosome exisitng as proviral DNA (latent state) for the rest of a person's life

transmission can occur

Term
HIV pathogenesis stage 3
Definition

chronic stymptiomatic HIV dx stage

virus replications destroy CD4 t cellss and their numbers decline and viremia increases

results in an immune repsonse w/ the onset of opprotunisitc infections and cancer

cd4 t cell counts frop below 200 per microliter of blood

cd4 and t cell count very important makrer of dx progression

transmission can occur

Term
hiv pathogenesis stage 4
Definition

crisis hiv dieases stage (aids)

virus replication contunues

marked destrucktion in cells of immune system

leads to marked immunodeficiency

px aquieies opprotunisitic infections and malignancies (cancer)

transmssion can occur

Term

HIV host cell tropism (preferential cell targets)

 

Definition

CD4+ T cells infectes, macrophages infected

two receptors required for viral entry: CD4 receptor or chemokine coreceptor-CCR5 in initial infections or CXCr4

Term
aquisistion and transmission HIV
Definition

sexual transmission

parenteral transmission

perinatal trasmission

transmitted during all 4 stages of disease

greatest risk stages 1 and 3

about 35% risk that HIV infected mothers will pass HIV to their babies

risk is reduced to 6% if tx is started before birth and 18% if started by 3 days

Term
genome sizes
Definition
viral genomes are small
Term
genome organization of HIV
Definition

gag, pal, and env are all in virus itself

all important drug targets

gag-makes capsid struc

pal-what codes for important enzymes **best for drug targets

env-2 proteins on surface

Term
viral replication
Definition
period from the first attachement of the virus to a cell through to the final maturation step after new virus buds off the cell
Term
Steps in HIV replication cycle (steps 1-5 of 11)
Definition

1.HIV viral attachment-envelope protein complex attaches to cd4 and the coreceptor (ccr5 or cxcr4)

2.virus endocytosed (uptake) into the cell

3. envelope complex promotes membrane fusion (late stage of entry) b/w the viral membrane and the cellular membrane

4. viral core is relaesed into the cytoplasm

5.virion assoc reverse transcriptase synth a double stranded DNA (cDNA) from the RNA genome

Term

 steps in HIV replication cycle (6-11 of 11)

 

Definition

6. cDNA (complementary DNA) migrates to the nucleus

7.enzyme integrase integrates it into the host cell genome (the inserted cDNA is called the provirus)

8.provirus transcribed to produce-genomic RNA; messenger RNA involved in production of virus specific proteins

9.assembly takles place in the cytoplasm

10. virions are release from cells by a process called budding

10. capsid struc changes create a mature virion (maturation)

Term
6 targets for drug tx HIV
Definition

1. receptor inhibitiors

2. fusion inhibitors

3. reverse transcriptase inhibitors

4. integrase inhibitors

5.protease inhibitors

6.maturation inhibitors (not approved clin use yet)

Term
drug resistance and HIV
Definition

reverse transcripase is error prone

HIV replication is rapid

therefore the mutation rate is very high

Term
HIV latency and reservoirs
Definition

HIV can hide in reservoirs and if retroviral therapy is stopped then the virus can remerge

HIV latency is a very important area of research including:
1.optimizing low level detection

2.identifying all latent reservoirs

3. reactivating from latency in order to identify and kill latently affected cells

Term
functional cure HIV
Definition

CCR5 deletion mutation found in patient that gave blood transfusion to px w/ HIV and leukemia and the levels of their virus dropped

promising concept but difficult to admin

Term
paramyxovirdiae
Definition

non segmented genome

same H and N surface proteins

examples are parainfluenza, mumps, measles

Term
orthomyxoviridae
Definition

segmented genome-allows reassortment

different H and N proteins

influenza

Term
influenza life cycle
Definition

has lipid bilayer which means it can be destroyed by soap

have mRNA polymerase on capsule which helps it reproduce on outside

Term
human parainfluenza virus
Definition

has 4 serotypes (1,2,3,4)
transmission through respiratory

replcation in respiratory tract

has no viremia and stays localized

clinical sx are croup-6mos to yrs, rhinorea

reinfections-common (transient immunity) no long term immunological immunity

lab dx is to detec t viral antigen in cells from nasal secretions

tx-no vaccine or anitviral drugs

Term
respiratory synctial virus (RSV)
Definition

important pathogen children and infants-most children get this by 2

transmission in respiratory tract

replicates in respiratory tract-no viremia

clinical sx-infacts (less than 6 months), bronchiolotis and pneumonitis

reinfections common

lab dx; detect viral antigen in cells of nasal secretion

Term
treatment and passive immunization for rsv
Definition

vaccine-non avail

antiviral drug-ribavin (fda approved aerosol)

passive immunization (doesn't induce immunity)-form of tx for an active infection

palivizumab-vaccine for high risk groups (expensive), preemie babies, babies w/ pulmonary probs

Term
mumps
Definition

paramyoxvirdae

childhood dx w/ one serotype

high rate subclincial infections

transmission-respiratory route, incubation period 12-20 days

replication: respiratory tract and lymph nodes (indicative of viremia)

clinical sx are fever, headache, pain, and swelling of one or both parotid glands

Term
complications, immune response, and dx of mumps
Definition

complication: orchitis-rare in childhood (20-30% of adults), blood in semen, or sterility in adults, meningitis, CNS involvement

immune response: lifelong immunity

dx-based on clinical sx

lab dx can be made: serodx igM antibodies (indicative of recent infection), IgG (acute v convalesncent stage)

Term
prevention mumps
Definition

live, attenuated vaccine

MMR

recomendation: first dose at 12-15 months of age and second around 4-6 years or 11-12 years of age

Term
morbillivirus
Definition

paramyxovirdae

aka morbilivirus, rubeola

acute febrile exanthematous dx

one of the most infectious diseases

only one serotype

 

Term
2 imporant facts about mumps
Definition

1. humans are the only natural host

2. no carrier state, therefore measeles could be eliminated as a human disease

 

Term

mumps transmission and clincial sx

 

Definition

transmission: respiratory route

incubation period: 10-14 days, infectious prior to sx

sx are the 3 C's; cough, coryza (inflammation of mucous membranes around nose), and conjunctivitis

koplik sports-roof of mouth to start, begin around day 3 before other sx, ulcerated membranes

warthin finkeldley synctial cells in cells of nasal secretions-packed full of viral particles

followed by viremia and maculopapular rash

Term
measles immunity, prevention, dx
Definition

immune response: lifelong immunity

lab dx; serodiagnosis HA test

prevention: live attenuated vaccine (MMR), 2 doses 1 at 12-15 months and the other at 4-6 years or 11-12 years old

Term
influenzavirus
Definition

orthomyxoviridae

1.respiratory infection accompanied w/ sig fever for 3-4 days, headaches, and myalgia, usually in winter, cases generally peak in february

2.contagious for about 1 day prior to sx appearing

3. 50,000 to 500,000 cases per year-highest infection rates in children

4.currently 4000 to 50000 deaths per year in the US (flu and assoc causes)-primarily in elderly, young children, px w/ med conditions

-h1n1 is an anamoly

Term
influenza a virion proteins
Definition

hemagglutinin (HA)-where most people develop immunity to this virus

RNA w/ 8 diff segments each with its own protein

Term
influenza trends
Definition

believed to be related to lower levels of immunity

dryer times lead to the spike in yearly transmission

Term
influenza serotypes
Definition

A, B, and C

serotypes a and b cause diease in humans

Term
reservoir for influenza
Definition

birds

water fowl believed to be asymptomatic reservoir (has it but doesn't cause disease)

land birds, pigs carriers as well

 

Term
nomenclature
Definition

antigentic type

host of origin

geographical origin

strain number

year of isolation

for influenza a, the hemagluttinin and neuraminidase antigen description in parantheses

ex; A/duck/Alberta/35/76 (H1N1)

Term
influenza pandemics
Definition

oldest known is russian (asiatic) flu in 1889

1918 worst (spanish flu) killing 20-100 million (h1n1)

first vaccine attentated pandemic was hong kong fly in 1968

2009 swine flu was most recent w/ 18,000 deaths

Term
antigenic drift
Definition

relatively error prone RNA polymerases create 1 error/10,000 bases (1/viral genome)

with every viriron particle having a mutation, this created plenty of doffer for evolution of influenza but with slow chance, vaccines and natural immunity show cross protection

Term
antigenic shift
Definition

when there is a coinfetion of mult influenza types (usually in fowl, rarely in pigs)

diff combos rna genome segment (8) can result in REASSORTMENT

new subtypes resulting are charac by their major antigenic determinants (hemaglutinin (H) and neuraminidase (N) types) often little or no cross protection-epidemics

Term

swine flu (h1n1)

 

Definition

first detected in april 2009 near pig farm in mexico

declared pandemic in june (first in 40 years)

predominant circulating strain in 2009-10 flu season

peaked # of cases in october (seasonal flu jan-march)

WHO declared pandemic over by august 10th 2010

Term
swine flu as a novel virus
Definition

quadrupple reassortment occured in pigs and contains segments from

1.north american swine flu (H)

2. North american avian flu (1)

3. human flu (N)

4. asian and euro swine flu (1)

transmission and clincal sx same as seasonal flu

virus has not mutated substantially and subsequent vaccines contain H1N1

Term
influenza treatment
Definition

amantadine and rimatadine inhibit viral uncoating (viral M2 protein)-these inhibit only influenza A strains, not B strains

neuramindiase inhibitors: prevent release of virions from infected cells-zanamivir-nasal inhalant, oseltamivir (tamiflu)-tablet-inihibit a and b

Term
influenza vaccine
Definition

all influenza vaccines contain

2 subtypes of a and 1 subtype of b

2 fda approved vaccines

1.innactivated vaccine for high risk group

2. live atteunated intranasal vaccine (viruses in LAIV are temperature sensitive mutants)

LAIV is only for healthy persons ages 2-49 years

not recommended for people w/ immune dysfunc, people with asthma, people on asprin therapy and pregnant women

Term
truth about antivaccine slides
Definition

not all vaccines produce immunity-some vaccines only 70% effective however recipients get disease a lot less severe

we were able to erradicate smallpox from the face of the earth with the use of vaccines

there is clear evidence for herd immunity substantially dec infection rates in uninfected populations

herd immunity plays a vital role in preventing dx in populations that can't receive vaccines

the toxins in vaccines are at marginal doses so they shouldn't concern recipients

Term
adenoviruses
Definition

iscosahedral non env capsids with 12 protein fibers with knobs involved in attachment to target cells

57 serotypes currently known

causes flu like, cold like sx, croup, bronchitis and sometimes GI distress, conjunctivitis, cystisis, and less commonly neurological dx

has 30-35 linear dsDNA genomes and encodes 22-40 proteins/ORFs

has resistance to drying (non env) and stable in pH/chem agents/physical agents making it able to have prolonged survival outside host

spread respiratory droplets, fecal routes

Term
adenoviruses genome depiction
Definition

has 3' to 5' genome dsDNA

has a TBP (terminal binding protein) at the 5' end

this is a mechanism which makes a copy of the oppostite strand

adenovirus also has early and later genes which can be transcribed and turned on later

Term
dx adenoviruses
Definition

antigen detection, PCR, virus isolation and serology

adenovirys typing is done using inhibition of hemagluttinin assay, or using type specific antisera, antibodies, or other molecular methods

possible causes of severe pneumonia cases or pneumonia outbreaks of unknown etiology

Term
treatment/prevention of adenoviruses
Definition

no vaaccine generally avail, types 4 and 7 vaccine was used before but were discontinued, oral vaccine for military use

use of infection control practices for general contact/droplet infections

sx generally mild, treated like other cold/flu infections

immunocompromised px can be treated with cidofovir

Term
cidofovir
Definition

used for treatment of adenoviruses

looks like nucleotide to viral DNA polymerase and virus tries to use this

most reasonable efficacy over other analogs

some toxicity in higher levels because host cells try to use this too

 

Term
mechanism to many of the nucleoside analogs
Definition

attaches to 3' hydroxyl group and many don't have this so it terminates the rest of the cahin

antivirals work bc they target the viral replication enzyme virus itself encodes

Term
papillomaviruses
Definition

PV infects mammals, birds, and possibly reptiles

isolated from filtrate of wart tissue

infection of primarily epithelial, but sometimes fibroblast cells

currently over 150 isotypes, 50-60 sexually transmitted, about 1/3 to 1/2 of those fall into high risk category

most common STI of viral origin, comparable to most common bacterial STIs, at any time, 20m americans in US have infection, 5.5M every year

Term
cervical cancer and papilloma virus
Definition

responsible for about 99% of cervical cancer, most penile and angogential cancers, and about 60% of oropharyngeal cancers

worldwide, half mill new cases cervical cancer/year, quarter mill deaths, in US 14,000 new cases, 5000 deaths (due to vaccine use, this number dropping)

Term
HPV virion
Definition

non env-like adeno, this is also resistant to drying etc

iscosahedral capsid

no viral proteins encapsulated-made of 2

55nm diameter-in theory probably could pass through latex

each capsomere is made up of 5 copies of viral protein L1-entergenically favorable

Term
HPV genome
Definition

8kb dsDNA GENOME

8 open reading frames

L1 and L2 are structural capsid proteins

E1 and E2 involved in HPV replication and transcriptional regulation

E6 and E7 are involved in immortilzation and escape from cell apoptosis

produced once they go into the cell

LCR (rgulatory region) contains viral origin of DNA replication

LCR contrains viral promoters for mRNA synth

Term
schematic of epidedermis and pappilomavirus
Definition

has to infect basal cells

the cells about the basal have no cell cycle

only cells active in epidermis are basal and these just get displaced to upper layers

Term
papillomavirus life cycle
Definition

release of mature virion

virion assembly

vegetative viral DNA replication

expression of late viral capsid proteins L1 and L2

expression of later viral proteins E4 and E5

establisment phase-est of primary infection

expression of intermediate early proteins E1, E2, E6, and E7

steady state viral DNA replication-50 to 100 episomal copies of genome

Term
immortalization and papiloma virus
Definition

causes by E7, causes targets degradation of cellular pRB (tumor supressing protein)

results in more cells producing virus

shut down cells=shut down virus so virus stops this process

Term
E7 process in cells
Definition

normally cells produce E2F which is a transcription factor which allows cells to grow

this factor will pause at phase G1 so cells don't grow uncontrollably (like outer epidermis)

pRM (tumor suppressor) is what pauses cells at G1

E7 takes away pRB so cells can continue to duplicate and bipass phase G1

Term

lack of cell cycle blok and apoptosis (programmed cell death)

 

Definition

caused by E6

targets degradation of p53 (tumor suppressor protein)

results in more cells producing virus

Term
p53 hijacking process and papilomavirus
Definition

in normal cells p53 produced at normal levels

viral infection, DNA damage or cell stress all cause levels of p53 to increase

this would then inc levels of BAX and cause Apoptosis

like using emergency brake on car-damages car but saves your life

E6 binds to p53 so the "emergency brake" never works and cell death does not occur

Term
end result of E6 and E7 protein process in papilomaviruses
Definition
hyperproliferation of epidermal cells resulting in hyperkeratosis characteristic of warts
Term

papillomavirus does not lyse cells but rather...

hijacks process of losing skin cells

Definition
Term
papiloma as std
Definition

probably has diff mech than passing through basal cells w/ mild abrasion

less layers to go through on yo dick

Term
how does HPV drive  cells to be cancerous
Definition

cells must be driven to proliferate (uncontrolled manner) and must not respond to DNA damage to stop cell cycle and or commit cellular suicide (prevent apoptosis)

e7 and e6 are the most critical oncogenes for HPV to cause cancer

Term
high expression e6 and e7 lead to
Definition

constantly proliferating cells (loss of pRB func)

lack of cell cycle control/DNA damage checkpoints (loss of p53 tumor suppressor)

lack of apoptosis which would kill damaged oncogenic cells (loss of p53)

resulting in cells primed for genomic/genetic instability

Term
prevention/treatment HPV infections
Definition

HPV vaccine-guardasil

HPV 6, 11, 16, 18 (all but 11 here are high risk), L1 proteins-"ghost" viral particles

cervarix (16 & 18)

current txs-removal-surgical, freezing, chemical etc trying to eliminate basal cells

imiquimod-immune stimulator, doesn't always work but shorten time for clearing

Term
types of antiviral agents
Definition

nucleotide analogs

inhibitors of proteases

inhibitors of retrovirus intregration

but none of these can work for HPV

Term
cancer treatments and HPV
Definition

prevention w/ the 2 HPV vaccines

PAP smears

surgical removal of lesions at early stages

radiations, various chemo agents

outlook still poor for those dx at later stage (about 50%)

Term
cancer and HPV
Definition

not part of normal HPV life

infrequent molecular accident but w/ virus being so commone, it nonetheless has become a frequent cancer

Term
polyomarviruses
Definition

look like papilomarviruses

not epidermal viruses-their life cycle not linked to differentiation, they usually have a normal 3-5 day lytic cycle

cell trophisms vary

45 nm non env iscoahedral capsids-72 capsomeres

circular dsDNA

encode 5 or 6 proteins (2 or 3 structural, and 2 or 3 non struc)

2 welll known are JC and BK viruses

both are very common (80%-get them as kids)-cause disease in immunocompromised

Term
polyomavirus genome
Definition

TCR is non coding region

large t antigen is functional protein (on same half as small t antigen)

other side encodes for various other proteins

Term
JC virus
Definition

neurologicl

progressive multifocal leukoencephalopahty in immunocompromised (white matter swelling-causes MS like sx)

happens in late stage aids

early normal infection probably like a tonsilitis

Term
BK virus
Definition

to kidneys, nephritis and neuropathy in kidney transplant px

most people get this while young but some people could still be excreting the active virus

Term
SV40
Definition

simian virus 40

effective at causing cancer in monkeys cells

became a model for many other cellular functions

Term
MCV
Definition

80% merkel cell carcinoma involved w/ this

found in immunocompromised/old people

 

Term

human herpes virus

 

Definition

8 types that infect humans

HSV1, HSV2, and varicella/zoster (VSV) are neurotrophic and infect from skin cells and go to nerve cells

epstein barr, cytomegalovirus, and herpes 6-8 infect lymph and immune system

Term
e
Definition
Term
herpesviridae
Definition

major feature of pathogenesis is that these viruses est latent infections

following an intial infection (primary), the virus establishes itself in a non infectious form in neural or lymphoid tissues and can reactivate to give a secondary (recurrent) infection which is often the major cause of disease

ubiquitous infections-most indiv are infected w/ 5 of the 8 human herpesviruses

Term
herpes virus struc
Definition

enveloped-can be disrupted by soap

not as resistant to drying

enveloped (lipid) covered w/ protein spikes-viral protein involved w/ attachement and structure

has inner tegument-has no real structure but has many important viral proteins carried to next host

Term
herpes genome
Definition

encode about 7-200 proteins alone ( larger than other viruses)

vary in sizes

does ciruclate in cell

many proteins and functions than other DNA viruses

Term
herpes lytic replication
Definition

has lytic cycle where it injects DNA into cell and replicates and releases mature virion

tegument proteins remain assoc until fuse w/ cell

early proteins-DNA replication

late-structural func

 

Term

HSV 1 and HSV 2

 

Definition

localized 1st infection very minor

travels along neuronal path and latent w very few viral proteins

generally occur when people are stressed (ex fighting a fever)

specific mech is still unknown

blisters tend to stay localized to the site of infection

Term
herpes blisters
Definition

HSV 1 can get transmitted to eye and cause induced keratitis

opaqueness can happen to cornea

second only to to trauma as cause of corneal blindness in US

kids can chew on fingers and transfer blisters to fingers, toes, etc ( why dental hygenists use gloves)

slight abrasion and herpres breaks out on wrestlers-herpes gladirorum-this can get transfered to face

Term
herpes and brain infections
Definition

usually doesnt cross BBB and occasionally does

HSV1 can cross trigeminal and cause herpes encephalitis

HSV2 can cross and cause meningitis

Term
neonatal HSV2 infection
Definition

contracted during passage through genital canal

contracted postnatally from indiv shedding virus

disseminated HSV infection to major organs and CNS

progression of infection to CNS results in death, MR, or neurologic disability even w/ tx-80% mortality in absence of antiviral therapy

tx w/ prophylaxis or ceasarian

Term
acyclovir and valacycolvir
Definition

 

acyclovir one of the best antivirals out there

valacyclovir has greater bioavail and used in prevention congential transmission

Term
VZV herpesviridae cycle
Definition

infection conjunctivits and or mucosa URT

viral replication in regional lymp nodes

primary viremia

viral replication in spleen, liver and other organs

secondary viremia

infection of skin and appearance of vesticular rash

Term

varicella rash

 

Definition

has marks that are full or virion

can get from touching one of these or from inhaling virus

Term
VZV latency and reactivation
Definition

zoster/shingles

reactivated from central nerves to skins and more toxic to neurological system than primary infection

can get pain from nerve damage ranging from years to lifetime

can also cause blindness if appears on face near eye

can cross placental barrier and cause limb atrophy in uterpo

Term

VZV intervention strategies

 

Definition

acylovir and valacyclovir

effective vaccines against varicella and zoster are avail and in use-vaccine against zoster about 50% effective

 

Term
lymphotrophic herpesviruses
Definition

viruses which infect cells of lympho-reticular system- T cells, B cells, monocyte/macrophages, dendritic cells

EBV, CMV, HHV6-8

Term
EBV
Definition

aka mono

invaces at cells and causes acute pharyngitis and has latent phase

goes into memory cells and can get reactivated by antigens

Term
cancers and EBV
Definition

burkitts lymphoma-found in areas where malaria infectious-possibly aggravates latent EBV

nasopharyngeal carcinoma-diets high in salt and fish in asia

could get reactivated w/ persistant infection of immunocomprosmised

Term
EBV and transplantation
Definition

post transplant lymphoproliferative dx

bone marrow and solid organ transfers

EBV transfered in graft

EBV infects recipient B cells

recipient EBV seroneg and under high levels of immunosupresion

transplant recipients and donors need to be EBV neg

Term
cytomegovirus
Definition

assoc w/ monocytes, polymorphonuclear lymphocytes and macrophages

primarily perinatal, and vereneal transmission

most infections in the normal host are asymptomatic or mild

spread by close contact, present in all body fluids

pop a risk; babies, embryos, immunocompromised, transplant recipients

major cause hearing loss and deafness in children

can cause worse dx in immunocompromised

**gancyclovir drug of choice

combo vaccine under development

Term
pircornavirdae
Definition

transmission via fecal/oral route

polio virus and coxsackie (A and B) viruses

one of the largest families of small ssTNA pos sense viruses

human pathogens include the following

enteroviruses-polio, coxsackie

rhinoviruses-common cold (more than 100 types)

herpnavirus: hep A

 

Term
rhabdovirdae
Definition
transmission via bite of rabid animal (zoonotic)
rabies virus
Term
reovirdae
Definition

transmission via fecal/oral route

rota virus

Term

 

 

Definition
Term
picronavirus pathogenesis
Definition

group of viruses causes effects after infecting gut

grow near oral part and seep into blood (primary viremia)

injest them

only infectious form humans therefore get from human feces (ex swimming pools)

can affect muscles, skin, brain meninges and liver

muscles can be problematic if heart muscle affected or breathing muscles affected

 

Term
poliovirus
Definition

transmitted fecal oral route (poor hygeine)

four outcomes: asymptomatic infections (90%), abortive polio, non paralytic polio, paralytic poliomyelitis

Term

abortive polio

 

Definition

minor illness

5% infections

3-4 days after, HV, fever, malaise, sore throat,

self limiting

recovery in days

Term

non paralytic polio

 

Definition

1-2% infections

virus infects CNS and meninges causing back pain, muscle spasms and minor illness sx

Term
paralytic poliomyeltities
Definition

.1%-2% infections

after the minor illness, a viremia occurs and virus infects spinal cord (anterior horn cells), motor cortex of brain

paralysis is based on extent of neural infection

one or all the 4 extremities infected

paralysis may result in complete recovery, residual paralysis or death

Term
bulbar poliomyeletis
Definition

severist form of paralytic poliomyelitis

involves muscles of pharynx, vocal cords, respiration, mortality 75%

iron lung chambers in the 1950s

 

Term
postpolio syndrome
Definition

may occur later life (30-40 years later)

20-80% of original victims

deteroriation in neurons-original affected muscles

no poliovirus is detected in these indiv

Term
polio vaccine
Definition

uses trivalent vaccine

includes serotypes: 1,2,3

killed-Salk inactivated vaccine (IPV)

Live-SAbine, live attenuated oral vacine (OPV)

in usa: only IPV is recommended

recommended at 4 doses at ages 2, 4, 6-18 months and at 4-6 years

Term
poliovirus eradication
Definition

the WHO currently pursuing a global eradication strategy for poliomyelitis

in 2010, there were 1300 cases worldwide

in 2011, 650, and in 2014, 358

endemic countries include pakistan, afghanistan, and nigeria

most of the world is now free of polio

traveller's vaccine?

Term
Coxsackieviruses
Definition
incluces coxsackie A and coxsackie b
Term
Coxsackie A and types
Definition

self limiting, no specific treatment

includes herpangina and hand foot and mouth disease

Term
herpangina
Definition
vesicular lesions in throat region, fever, sore throat
Term
hand-foot-and-mouth disease
Definition
vesicular lesions on hands, feet, mouth, and tongue
Term
coxsackie B virus
Definition

pleurodynia (Bohnholms disease)

myocardial and pericardial infections

Term

pleurodynia (bohnholms disease)

 

Definition

severe pleurtic chest pain (4 days)

fever

vomiting

Term
myocardial and pericardial infections
Definition

cardiomegaly

hepatomegaly

tachycardia

fever

 

Term
coxsackievirus vaccine
Definition
none avail
Term
rabies
Definition

ssRNA negative sense, bullet shaped and is the most important human pathogen in the gamily

zoonotic infection-no spread human to human

reservoir=wild animals, unvaccinated dogs/cats

major source is saliva in bite/lick of rabid animal (ex dog bites and teeth put saliva in bone)

minor source is aerosols in bat (rabid) caves

Term

major infected animals

 

Definition

raccoon bats skunks

dog cat cattle

Term
pathogenesis of rabies
Definition

virus inoculated

viral replication in muscle

virion enters peripheral nervous system

replication in dorsal ganglia

rapid ascent in spinal cord

infec of spinal cord, brain stem, cerebellum, and other brain struc

can take a year to set in

while asymptomatic can be vaccinated to offset

doesn't like to grow anywhere but nerves

can do swallow test to see if in brain and if those nerves infected

Term

clinical stages rabies

 

Definition

long incubation period: weeks, months, during which virus replicates

prodrome stage (2-10 days): virus infects peripheral nerves and travels via spinal cord to brain

neurologic stage: 2-10 days virus spreads to eyes (cornea), salivary glands, skin, and other organs, hydrophobia, seizures, disorientation, hallucination

comatose stage and death: the neurologic stage almost always leads to death due to neurologic and respiratory failure

once sx appear-universally fatal

Term
lab dx
Definition

once the neuro sx begin, death inevitable and intervention no longer useful

lab tests to confirm clinc dx in px or if animal was rabid (post mortem)

viral antigen detection by immunoflourensce in brain or skin biopsy materail is widely used in animals

ELISA assays are also used for ex to check the vaccination status of an indiv

rabies case was found in toronto from domicican in 2012

Term
post exposure rabies treatment and prophylaxis
Definition

1.wash wound immed w/ soap and water

2.immunize w/ vaccine (one arm) in combo w/ admin of one dose of human rabies immunoglobulin (HRIG) in other arm

passive immunization (HRIG) provides antibodies until px produces antibodies in response to vaccination

 

Term
human rabies vaccine
Definition

vaccine made in human diploid cells (HDCV)
and virus is chem inactivated (also can be made in chick cells) (PCECV)

current vaccine is safe and effective

post exposure vaccine

HDCV is admin IM on day of exposure, and then on days 3, 7, 14, (+RIG, dO)

pre exposure vaccine: days 0, 7, 21/28 (no RIG)

Term
prevention of human rabies
Definition

1.key to prevention in humans is effective control of rabies in domestic (all cats and dogs must be vaccinated) and wild animals

2. a live recombinant vaccina virus vaccine expressing rabies virus G protein (envelope spike) is approved for use w/ wild animals

vaccine is injected in a bait and parachuted into forest, successfully immunized raccoons, foxes and other wild animals

Term
viral diarrhea
Definition

rotavirus

many viruses cause diareha

rota viruses are the major cause of infantile diareha worldwide

noroviruses (calcivirus) are major prob for older children and adults (cruise ships)

rotaviruses have an 11 segment dsRNA genome are relativeley stable at room temp and a wide range of pH in GI tract

Term
rotaviruses
Definition

human disease is causes by group A and occasionally by group B and C rotaviruses

wheel shaped disease

transmission fecal-oral route

replication in epithelial cells of small intestine preventing the absorption of water and thus causing watery diareha

in undernourshed children-risk of dehydration and death (developing countries)

about 3m cases in the us prevaccine

Term
clincial syndrome rotaviruses
Definition

incubation period- 24-48 hours

major clincial sx are fever, vomiting, diarrhea and dehydration

large amounts of viruse released in stool

about 5 mill deaths worldwide (dehydration)

US: 2.7 mill cases about 50 deaths before vaccine

dx: commonly used techniques:

1. detect viral antigen in patients stool sample by enzyme immunoassay (ELISA)

2. PCR on stool sample

Term
rotavirus treatments and vaccines
Definition

general tx: supportive therapy, rehydration kits to replace fluid/salts

vaccines: recommended (US); WHO now recommends worldwide:

1.rotarix-human live monovalent (2,4 mo)
2. rotateq-bovine live pentavalent (2,4,6 mo)

control:wash hands and isolate known cases

Term
Emerging and reemerging viral dx
Definition

defined as infections that have newly appeared (ex HIV) in a pop or have existed but are rapidly inc in incidence or geographic range (ex denge)

global resurange in zooinotic viral diseases (transmitted by animals to humans). about 75% of emergin agents are zooinotic

Term
specific factors contributing to emerging an remerging dx
Definition

speicifc factors precipitating disease emergence can be identified in virtually all cases such as

ecological/enviro: interaction b/w organisms and their natural environment ex: farm animals and swine flu

demographic: populations that may be at increased risk of contact with previously unfamiliar agent or its natural host to promote dissemination ex-air travel now common but wasnt in past

Term
factors contributing to dengue virus, west nile, SARS
Definition
transportation/travel, urbanization, migration
Term
factors contributing to malburg virus
Definition

importation of monkeys to malburg germany from jungle

no cases in USA as of yet

Term
Hantavirus contributing factors
Definition

enviro changes in USA

in S korea, inc contact w/ rodent hosts (expansion or rice fields-rodent area)

Term
factors contributing to HIV/AIDS
Definition

travel, sexual transmission, IV drug use, congential

horizontal and vertical factors

Term
safety and viruses
Definition

many of these viruses are dangerous and need containment

BSL4 highest level

BSL3 bad but not as dangerous

need hazmat suits

Term
Nipah Virus
Definition

memeber of paramyxovirdidae (neg sense RNA (compliment to mRNA) genome) (like measles virus)

first reported in malaysia in 1999

outbreak of fatal febrile encephalitis and respiratory illness in older men

remerged in bangladesh in 2001 w/ high mortality rate

reservoir-fruit bat

transmission is humans via intermediate host, pig or pig products

human to human

Term

clincial symptoms of nipah virus infection

 

Definition

incubation period of 3-14 days

followed by drowsiness and disorientation and mental confusion

some paitients may experience respiratory illness during this stage  (can get into lungs)

encephalitis can progress to coma and death w/in 1-2 days

also causes serious disease in pigs

no vaccine and ribavin generic antiviral can decrease mortality a little bit

Term
dengue and west nile viruses
Definition

both belong to family flavivirdae (most of which are arboviruses (arbo=insect, transmitted by insects)

ssRNA (Pos sense) viruses, replication sim to poliovirus

transmission via various birds and animals (reservoirs) w/ mosquito vectors

no vaccine

no antiviral agents

look like small non descript round

Term
Transmission of flaviviruses
Definition

st louis-west nile

transmits bidirectional culex mosquito and only to humans (we don't make enough virus to get back to the mosquito)

dengue (yellow fever) goes primate to mosquito and Aedes mosquito and back (jungle cycle); also goes aedes mosquito to human and back (urban cycle)

Term
dengue
Definition

first observed in 1780 asia, africa, and north america (southern US)

a very commone dx worldwide that is remerging as mosquitos (vector) spread (300 mill people every-pop of entire US)

reservoirs of dengue virus are humans and primates

clin sx are dengue fever (febrile rash) and dengue Hemorhaggic fever (DHF) or shock syndrome DSS

first mosquito/strain gets you the rash and a second strain/mosquito gets you the second (DSS or DHF)

DHF and DSS are serious illness that occur when ppl get infected serially w/ 2 diff strains (high mortality)

prevention: avoid mosquitos

Term
dengue distribution
Definition

in the 1930s, dengue was pretty widespread in south american and southern US

disappeared in 70s because of DVT but was taken off market because of enviro problems

now widespread again because we never found a replacement for DVT and also people cutting down the rainforest are moving into to mosquito areas

Term
west nile birds
Definition
1999 birds were falling out of the air dead and disease spread rapidly in a month
Term

west nile virus

 

Definition

first case in 1937 in west nile district of uganda

since spread worldwide-africa, europe, middle east, and nyc in 1999

believed infected birds were smuggled in from middle east

spread to all lower 48 states in US as well as canada and mexico in several years since

clincial sx are encephalitis (fatal in elderly), no human to human since level virus low

no vaccine low

most infections asymtomatic

Term
hantaviruses
Definition

family: bunyavirdae

virus: ssRNA  (- sense) 3 segments

first isolated from field mouse in koreas hantaan river

causing hemorrhagic fever w/ renal syndrome (HFRS) w/ up to 10% case/fatality; virus spread directly from small animals through inhalation of dried fecal material and urine

since that time, the virus has causes HFRS in ASia and europe

four corners dx was this in the US in 1993

Term
id of mystery illness of 1993
Definition

new strain of hantavirus-sin nombre virus and the dx is called hantavirus pulmonary syndrome (HPS)

reservoir: small mammals (mice and rats)

transmission: respiratory route by inhalation of virus present in the excreta (feces, urine, respiratory secretions from infected animals)

human to human transmission not documented in USA

Term
clinical sx of hantavirus pulmonary syndrome
Definition

incubation period is 1-5 weeks

early sx-fatigue, fever, muscle aches, headache and vomiting

late sx-4-10 days later-coughing, shortness of breath and severe respiratory depression that kills w/in hours

high rate of mortality (15-50%), depending on the virus strain

antiviral agent-none

vaccine-hantavax developed in USA but not approved by FDA

Term
why hps emerged in 1993
Definition
snow in sierras led to increase in the deer mouse population
Term
disease in china
Definition

there are major annual outbreaks in china of hemorrhagic fever w/ renal syndrome caused by hantaviruses

major virus is hantaan virus

Term
ebola and marburg viruses
Definition

family: filoviridae (long thread like particles)

ebola first emerged in the 70s near ebola river in Zaire

marburg virus appeared in marburg, germany in 1967-monkeys from uganda

outbreaks in africa on a regular basis-killing several 100 people both cause hemorrahagic fever in africa, both viewed as excellent bioweapon agents

reservoir: fruit bat

transmission repiratory or fecal oral, human to human efficient

clin sx: early flu illness, later hemorrhagic lesions on various organs w/ extensive internal bleeding mortaltity rate very high

no vaccine or antiviral

Term
ebola and marburg outbreaks
Definition

there viruses have been recogonized for about 40 years but are liklely to be more ancient

on a regular basis outbreaks of both viral dx have occured in central africa

ebola>marburg

both cause highly fatal hemorrhagic fever

in 2014 a major outbreak of ebola spread to several countries in west africa

march 2015: liberia now ebola free but sierra leone and guinea still problematic

about  14k cases total and 10k deaths

Term
summary ebola and marburg viruses
Definition

reservoir fruit bat; person to person

3 day to 3 week incubation period

fever, severe headache, muscle pain, diarehha, vomitting, hemorrhagin

case/fatality rate is 60-80%

if you recover, you are protected

Term
chikungungya virus
Definition

an alphavirus

causes fever, joint and muscle pain, rash

rarely fatal but often chronic

major indian outbreak

2500 cases in USA in 2014

25000 cases in the caribbean in 2014

mosquito borne

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