exam 4 – Microbiology – Flashcards
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racaniello |
viruses |
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 |
virus particle size |
around 100 namometers like holding an orange in a circus tent (mammalian cell) |
virus classification |
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) |
Baltimore classification |
codes the many different ways virus can get from genome to protein |
virus structure simplified |
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 |
protein coat/capsid |
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 |
what is a virus |
nucleic acid-RNA or DNA, single or double strands, circ or linera protein coat (capsid)-helical or iscosahedral, subunit construction envelope-present or not |
diversity of structure |
can be very diverse in structure shape and size |
three advantages of virion structures |
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 |
virus capsid struc |
protein subunit construc based upon hydrophobic and electrostatic interactions make up the two basic struc or iscoasahedral (hexagon like shape) or helical |
4 steps viral life cycle |
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 |
toll of virusal diseases |
have endemics and outbreaks worldwide problems can get better with vaccines |
what is an antibody (and the 2 we need to know) |
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 |
general sx of any hep infection |
yellow tint to eyes and skin, inflammed stomach, espophogas liver stomach spleen pancrease, edema in legs, numbness, tingling |
hep a virus |
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) |
clinical picture HAV infection |
can be excreted in feces before even clinical illness develops IgM detected first IgG for life ALT levels elevated |
HAV tx and prevention |
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 |
Hep B virus |
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 |
viral hep B (misc) |
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 |
clincial pic HBV (3 types infection) |
acute, asymptomatic, chronic |
asymptomatic infection |
majority of infections are asymp, HBsAg in serum for short time (1-2 months) antibodies against HBsAg persist for life providing lifelong immunity |
acute HBV infection |
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 |
chronic hbv |
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 |
hbv tx |
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 |
HBV prevention |
passive immunity-hep b immune globulin, standarf immune serum globulin active immunity-immunizations |
hep c |
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 |
clincial picture of Hep c |
most infections are insidious (slow) time to clinical hep greater than 10 years time to cirrohis and cancer a couple decades
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hcv treatment and prevention |
combo of antiviral ribavirin for 24-48 weeks depending on HCV genotype, most effective 1st 6 months after infection as opposed to chronicity |
hep d |
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) |
hep d tx |
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 |
hdv prevention |
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 |
hep e |
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 |
HEV prevention and treatment |
treatment-none avail usually self limiting, hospitilzation required for px w/ fulminant dx prevention-maintain safe public water sanitation, proper disposal of waste |
central dogma molecular biology |
DNa is the start (orginal design of a machine from a factory) made into RNA (blueprints of the machine) 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 |
retrovirus |
virus that undergoes reverse transcription of RNA into DNA during the viral lifecycle (HIV) |
endogenous retroviruses |
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 |
this week in virology article |
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 |
HIV/aids |
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 |
2 human speicies of HIV |
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 |
lab dx HIV
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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 |
hiv pathogenesis stage 1
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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 |
hiv stage 2 |
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 |
HIV pathogenesis stage 3 |
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 |
hiv pathogenesis stage 4 |
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 |
HIV host cell tropism (preferential cell targets)
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CD4+ T cells infectes, macrophages infected two receptors required for viral entry: CD4 receptor or chemokine coreceptor-CCR5 in initial infections or CXCr4 |
aquisistion and transmission HIV |
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 |
genome sizes |
viral genomes are small |
genome organization of HIV |
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 |
viral replication |
period from the first attachement of the virus to a cell through to the final maturation step after new virus buds off the cell |
Steps in HIV replication cycle (steps 1-5 of 11) |
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 |
steps in HIV replication cycle (6-11 of 11)
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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) |
6 targets for drug tx HIV |
1. receptor inhibitiors 2. fusion inhibitors 3. reverse transcriptase inhibitors 4. integrase inhibitors 5.protease inhibitors 6.maturation inhibitors (not approved clin use yet) |
drug resistance and HIV |
reverse transcripase is error prone HIV replication is rapid therefore the mutation rate is very high |
HIV latency and reservoirs |
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: 2.identifying all latent reservoirs 3. reactivating from latency in order to identify and kill latently affected cells |
functional cure HIV |
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 |
paramyxovirdiae |
non segmented genome same H and N surface proteins examples are parainfluenza, mumps, measles |
orthomyxoviridae |
segmented genome-allows reassortment different H and N proteins influenza |
influenza life cycle |
has lipid bilayer which means it can be destroyed by soap have mRNA polymerase on capsule which helps it reproduce on outside |
human parainfluenza virus |
has 4 serotypes (1,2,3,4) 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 |
respiratory synctial virus (RSV) |
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 |
treatment and passive immunization for rsv |
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 |
mumps |
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 |
complications, immune response, and dx of mumps |
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) |
prevention mumps |
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 |
morbillivirus |
paramyxovirdae aka morbilivirus, rubeola acute febrile exanthematous dx one of the most infectious diseases only one serotype
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2 imporant facts about mumps |
1. humans are the only natural host 2. no carrier state, therefore measeles could be eliminated as a human disease
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mumps transmission and clincial sx
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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 |
measles immunity, prevention, dx |
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 |
influenzavirus |
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 |
influenza a virion proteins |
hemagglutinin (HA)-where most people develop immunity to this virus RNA w/ 8 diff segments each with its own protein |
influenza trends |
believed to be related to lower levels of immunity dryer times lead to the spike in yearly transmission |
influenza serotypes |
A, B, and C serotypes a and b cause diease in humans |
reservoir for influenza |
birds water fowl believed to be asymptomatic reservoir (has it but doesn't cause disease) land birds, pigs carriers as well
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nomenclature |
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) |
influenza pandemics |
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 |
antigenic drift |
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 |
antigenic shift |
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 |
swine flu (h1n1)
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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 |
swine flu as a novel virus |
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 |
influenza treatment |
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 |
influenza vaccine |
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 |
truth about antivaccine slides |
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 |
adenoviruses |
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 |
adenoviruses genome depiction |
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 |
dx adenoviruses |
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 |
treatment/prevention of adenoviruses |
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 |
cidofovir |
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
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mechanism to many of the nucleoside analogs |
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 |
papillomaviruses |
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 |
cervical cancer and papilloma virus |
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) |
HPV virion |
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 |
HPV genome |
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 |
schematic of epidedermis and pappilomavirus |
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 |
papillomavirus life cycle |
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 |
immortalization and papiloma virus |
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 |
E7 process in cells |
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 |
lack of cell cycle blok and apoptosis (programmed cell death)
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caused by E6 targets degradation of p53 (tumor suppressor protein) results in more cells producing virus |
p53 hijacking process and papilomavirus |
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 |
end result of E6 and E7 protein process in papilomaviruses |
hyperproliferation of epidermal cells resulting in hyperkeratosis characteristic of warts |
papillomavirus does not lyse cells but rather... hijacks process of losing skin cells |
papiloma as std |
probably has diff mech than passing through basal cells w/ mild abrasion less layers to go through on yo dick |
how does HPV drive cells to be cancerous |
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 |
high expression e6 and e7 lead to |
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 |
prevention/treatment HPV infections |
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 |
types of antiviral agents |
nucleotide analogs inhibitors of proteases inhibitors of retrovirus intregration but none of these can work for HPV |
cancer treatments and HPV |
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%) |
cancer and HPV |
not part of normal HPV life infrequent molecular accident but w/ virus being so commone, it nonetheless has become a frequent cancer |
polyomarviruses |
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 |
polyomavirus genome |
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 |
JC virus |
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 |
BK virus |
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 |
SV40 |
simian virus 40 effective at causing cancer in monkeys cells became a model for many other cellular functions |
MCV |
80% merkel cell carcinoma involved w/ this found in immunocompromised/old people
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human herpes virus
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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 |
e |
herpesviridae |
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 |
herpes virus struc |
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 |
herpes genome |
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 |
herpes lytic replication |
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
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HSV 1 and HSV 2
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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 |
herpes blisters |
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 |
herpes and brain infections |
usually doesnt cross BBB and occasionally does HSV1 can cross trigeminal and cause herpes encephalitis HSV2 can cross and cause meningitis |
neonatal HSV2 infection |
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 |
acyclovir and valacycolvir |
acyclovir one of the best antivirals out there valacyclovir has greater bioavail and used in prevention congential transmission |
VZV herpesviridae cycle |
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 |
varicella rash
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has marks that are full or virion can get from touching one of these or from inhaling virus |
VZV latency and reactivation |
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 |
VZV intervention strategies
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acylovir and valacyclovir effective vaccines against varicella and zoster are avail and in use-vaccine against zoster about 50% effective
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lymphotrophic herpesviruses |
viruses which infect cells of lympho-reticular system- T cells, B cells, monocyte/macrophages, dendritic cells EBV, CMV, HHV6-8 |
EBV |
aka mono invaces at cells and causes acute pharyngitis and has latent phase goes into memory cells and can get reactivated by antigens |
cancers and EBV |
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 |
EBV and transplantation |
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 |
cytomegovirus |
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 |
pircornavirdae |
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
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rhabdovirdae |
transmission via bite of rabid animal (zoonotic) rabies virus |
reovirdae |
transmission via fecal/oral route rota virus |
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picronavirus pathogenesis |
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
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poliovirus |
transmitted fecal oral route (poor hygeine) four outcomes: asymptomatic infections (90%), abortive polio, non paralytic polio, paralytic poliomyelitis |
abortive polio
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minor illness 5% infections 3-4 days after, HV, fever, malaise, sore throat, self limiting recovery in days |
non paralytic polio
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1-2% infections virus infects CNS and meninges causing back pain, muscle spasms and minor illness sx |
paralytic poliomyeltities |
.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 |
bulbar poliomyeletis |
severist form of paralytic poliomyelitis involves muscles of pharynx, vocal cords, respiration, mortality 75% iron lung chambers in the 1950s
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postpolio syndrome |
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 |
polio vaccine |
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 |
poliovirus eradication |
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? |
Coxsackieviruses |
incluces coxsackie A and coxsackie b |
Coxsackie A and types |
self limiting, no specific treatment includes herpangina and hand foot and mouth disease |
herpangina |
vesicular lesions in throat region, fever, sore throat |
hand-foot-and-mouth disease |
vesicular lesions on hands, feet, mouth, and tongue |
coxsackie B virus |
pleurodynia (Bohnholms disease) myocardial and pericardial infections |
pleurodynia (bohnholms disease)
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severe pleurtic chest pain (4 days) fever vomiting |
myocardial and pericardial infections |
cardiomegaly hepatomegaly tachycardia fever
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coxsackievirus vaccine |
none avail |
rabies |
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 |
major infected animals
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raccoon bats skunks dog cat cattle |
pathogenesis of rabies |
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 |
clinical stages rabies
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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 |
lab dx |
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 |
post exposure rabies treatment and prophylaxis |
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
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human rabies vaccine |
vaccine made in human diploid cells (HDCV) 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) |
prevention of human rabies |
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 |
viral diarrhea |
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 |
rotaviruses |
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 |
clincial syndrome rotaviruses |
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 |
rotavirus treatments and vaccines |
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) control:wash hands and isolate known cases |
Emerging and reemerging viral dx |
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 |
specific factors contributing to emerging an remerging dx |
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 |
factors contributing to dengue virus, west nile, SARS |
transportation/travel, urbanization, migration |
factors contributing to malburg virus |
importation of monkeys to malburg germany from jungle no cases in USA as of yet |
Hantavirus contributing factors |
enviro changes in USA in S korea, inc contact w/ rodent hosts (expansion or rice fields-rodent area) |
factors contributing to HIV/AIDS |
travel, sexual transmission, IV drug use, congential horizontal and vertical factors |
safety and viruses |
many of these viruses are dangerous and need containment BSL4 highest level BSL3 bad but not as dangerous need hazmat suits |
Nipah Virus |
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 |
clincial symptoms of nipah virus infection
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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 |
dengue and west nile viruses |
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 |
Transmission of flaviviruses |
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) |
dengue |
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 |
dengue distribution |
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 |
west nile birds |
1999 birds were falling out of the air dead and disease spread rapidly in a month |
west nile virus
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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 |
hantaviruses |
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 |
id of mystery illness of 1993 |
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 |
clinical sx of hantavirus pulmonary syndrome |
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 |
why hps emerged in 1993 |
snow in sierras led to increase in the deer mouse population |
disease in china |
there are major annual outbreaks in china of hemorrhagic fever w/ renal syndrome caused by hantaviruses major virus is hantaan virus |
ebola and marburg viruses |
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 |
ebola and marburg outbreaks |
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 |
summary ebola and marburg viruses |
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 |
chikungungya virus |
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 |