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Last 4 lectures of semester 3

What family do the human T-lyphotropic viruses belong to? deltaretroviridae
Adult t-cell leukemia/lymphoma can be caused by what virus? HTLV-1 (Human T-lymphotrophic virus-1 - a deltaretroviridae member)
a rare viral form of hairy cell leukemia is caused by what virus? HTLV-2
HIV-1 and HIV-2 are part of what family? lentiviruses
Are retroviruses DNA or RNA? Haploid or Diploid? Diploid, ssRNA. Two identical (+)SSRna molecules. HOMODIMER
Describe the retroviral genome homodimer. Diploid. Two postive SSRNA
Describe the contents of a retroviral capsid two identical (+)SSRNA, multiple copies of reverse transcriptase, integrase, and viral protease proteins.
Where are viral spikes located? In the envelope
Describe the composition of viral spikes composed of a recptr-bndng domain (gp120) and a transmembrane domain (TM; gp41). Each spike is composed of three identical TM proteins (homotrimer) making the stalk of the receptor and three identical SU proteins (homotrimer) making the rcptr-bndng domain
How many open reading frames are contained in the genome of a SIMPLE retrovirus (ie; Maloney Murine Leukemia (MLV? How are they arranged 3 ORFs, they are flanked on both sides by Long Terminal Repeats
What do the ORFs each code for? ENV, GAG, and POL
The ORF "tat" is found in what virus. What does it encode for? it is a regulatory protein found in HIV, induces cell cycling in host T-cell
The ORF "tax" is found in what virus. What does it encode for? it is a regulatory protein found in HTLV, induces cell cycling in host T-cell
What virus causes Tropical Spastic Paraparesis (HAM/TSP), (weakness in lower extremities) HTLV-1
List 5 dz asso with HTLV-1 1. Alveolitis (Inflammation of the lung alveoli)2. Polymyositis/dermatomyositis (Inflammation of muscle tissue)3. Arthritis (Inflammation of the joints)4. Uveitis (Inflammation of the eye)5. Dermatitis (Skin inflammation)
What is the microscopic appearance of T-cell infected with HTLV-1 Flower cells; characterized by the presence in the peripheral blood of malignant T-cells that have highly indented or lobulated nuclei (flower cells).
What are the endemic areas of HTLV-1 areas for HTLV-1 infection are Asia (especially southwestern Japan),
How is HTLV-1 transmitted? xmssion of the virus is through direct cell-to-cell contact between an infected individual and an uninfected individual and occurs via sexual intercourse, breastfeeding or parenterally (i. e. through blood transfusion/needle sharing/needlestick puncture).
What human cell type is HTLV-1 dependent on for replication HTLV-1 viral multiplication primarily relies upon T-lymphocyte replication, i. e. HTLV-1 chiefly replicates as a provirus during T-lymphocyte cell division.
What viral protein does HTLV--1 use to induce cell cycling? tax
Viral fitness of HTLV-1 depends on... Viral fitness therefore depends on the capacity of the virus to induce cell cycling, which is mainly mediated by the viral protein Tax.
How does tax work? transactivator that interacts with the cellular transcription factors that bind the proviral LTR, also increase expression of proteins involves with growth of tcell (IL-2/IL-2R, IL-15/IL-15R, Egr-1 and Egr-2 )
HIV predominately infects what 2 cell types T-lymphocytes and cells of the mononuclear phagocyte system (mainly macrophages)].
What are the two main types of HIV particles AND THE FUNCTION OF EACH? Macrophage-tropic (M-tropic) and T-lymphocyte-tropic (T-tropic). M-tropic viruses are responsible for the xmission of the virus, whereas T-tropic viruses occur later in the infxion and are rspnsble for the observed CD4+ T-cell destruction seen in AIDS
What carries an HIV virus from site from entry (mucosal surface) to site of replication (2ry lyphoid tissues) dendritic cells
What receptor does HIV bind to upon entering at the mucosal layer Upon entry, viral gp120 (SU) binds dendritic cell-specific ICAM3-grabbing nonintegrin (DC-SIGN) on the surface of a dendritic cell.
What are the two ways in which a HIV virus can be carried into 2ry lymphoid tissues? as is by transcytosis or bound to the cell surface, without viral replication in the dendritic cell; this is most likely to be the situation) or in trans (i. e. with viral replication occurring inside the dendritic cell)
Once transported by the carrier cell into the 2ry lymhpoid tisues, what does the virus bind to on the t-cell? IT BINDS FIRST TO CD4+ receptor. --> induces recruitment of CCR5 / GP120 conf change the intact virus is likely transmitted by direct contact with a CD4+ T-lymphocyte that carries CCR5 on its surface, like a runner passing the baton during a relay.
What triggers the replicative cycle of HIV The rep. cycle begins when gp120 binds CD4+. Binding of gp120 with CD4+ induces a confrm. change in CD4+, allowing CD4+ to recruit a chmkne receptor (co-recptrr; first CCR5then CXCR4 later in the infxion)in the area of gp120,-> brings cell membrane closer
Through what structure does HIV enter a cell? Entry occurs through the fusion pore and is rapidly followed by uncoating.
What age group is HTLV most common in? Older people. Because of the viruses extremely long life cycle, by the time pt presents with symptoms they are very old. It is acquired via cell to cell contact (ie; breastfeeding) so they likely acquired it very a very young age.
72y/o presents with flower cells. How did he most likely acquired this dz. What is the causative agent? HTLV. Most likely acquired during breastfeeding as a child. (virus has VERY long replication cycle, takes long time to show signs of disease)
Why is the replicative cycle of HTLV so long? Because tax protein (responsible for inducing cell cycle) is expressed in such large numbers, CD8 cells are able to mount a very efficient response to kill the infected cells. Eventually tax expression by infected cells because 'invisible' to CD8+ cells
Lab dx of HTLV is done by what two markers? CD4+, CD25+ cells.
CD25+ = Flower cell (along with CD4+) = HTLV infxon
Tx of HTLV CHOP therapy
diference b/w HIV1 and HIV2 Same, except for HIV2 has longer replicative cycle... less morbidity.
Most common clade of HIV? B clade
How is HIV vertically transmitted? transplacentally or via breastmilk. AZT therapy has 90% of PREVENTING transmission to fetus.
Enter into the cell is accomplished by what change in the cell membrane Fusion of two points on the cell membrane
What is the function of GP41? Viral envelope protein. Harpoons the host cell. Embedded in lipid bilayer
What is the function of p24? Viral retangular nucleocapsid protein
In what direction to viruses assemble (outside -> inside or inside-> outside)? Outside -> inside
Protease inhibiting drugs block what phase of the replicative cycle? Block maturation.
What is the envelope precursor? What does it give rise to? Precursor = gp160. GP160 --> gp120 + gp 41
What is the function of gp120 other viral envelope protein. Sits outside as a "button" outside of the lipid bilayer of the the virius
What are the three precursor RNAs prior to maturation? gp160gag/pol precursor, gp160env precursor, pr55gag precursor (so... 160,160, and 55) These get cleaved into their idividual components during maturation
What is the HIV screening test? What is confirmation test? ELISA = screening (do test twice to r/o error). Western blot = confirmation
Describe the process of an HIV western blot test Standardized HIV protein is ran on a gel and then blotted onto cellulose paper. This is then washed with pt serum, follow by radiolabled Ab against pt antibodies. Illuminecence (bands) indiates the presence of antibodies against HIV proteins.
What are the required findings of a western blot to dx HIV? atleast TWO of the three possible bands. (ANY TWO: ***P24, gp41, gp120, gp160*** )
What proteins are evaluated in western blot HIV test? P24, gp41, gp120, gp160
During what stage of infection do viral modifications occur as a result of poor proofreading of DNA pol? During the chronic stage of inxon (stage b/w initial and AIDS stage (CD4<200))
AIDS is dx'd as what CD4 level? CD4+ count <200
What cells are infected by HIV? CD4 and CD8 cells! (mechanism unknown for CD8, but they are disabled somehow)
oppurtunistic infxons are characteristic of what stage of HIV infxon? AIDS stage (the stage that comes AFTER chronic stage)
What symptoms characterize the chonic stage of HIV infxon? This stage is usually asymptomatic.
Describe the characteristic symptoms / signs of each stage of HIV infxon... Primary infxon stage (acute phase - 3-4 months): mono-like symptoms. fever, malaise, etc). Chronic phase: asymptomatic. AIDS: oppurtunistic diseases and herpesvirus recurrances
Describe the genome of Herpesvirus linear daDNA, 46-235 bp
How many bp is herpes virus? 46-235 bp
What is MIC? Minimum inhibitory concentration: The lowest concentration of an Ab that will STOP growth.
What is MBC? Minimum bacteriocidal concentration: The lowest concentration of an Ab that will kill growth
What is bacterial tolerance ? When an antibiotic goes from being bacteriocidal to bacteriostatic.
In general and more often than not,point mutations are usual (beneficial or detremental) to a cell? Detremental.
What is meant by selective pressure, with regards to ABx resistance? Selective pressure is the driving for for selection that is present when a drug is present in a growth medium. The presence of the drugs selects for features of resistance. The absence of this prssure, traits can be lost
How areauired trais lost? In the absence of antibiotic (for example), the trait (resistance) offers no advantage, and since plasmids do not split equally, dome daughter cells will no get the trait. They will grow fast and will eventualy outcompete the cells that have the trait
What is an example of compensation in bacteria? A mutation that restores fitness so as to make resistance PERMANENT. (often times becoming resistant to a drug decreases fitness b/c of the increased time required for cell division)
What are OMPS? What mechanism of resistance are they involved in? OMP= outer membrane porin. They are involved in decreasing permeability to abx
WHat is th mech. by which vanc. resistanct MRSA aquired it's resistance. BY target modification...increasing the amount of target--> increases minimum inhib concentration (MIC) OR by altering PG
Where does vancomysin target? At the D-ALA D-ALA ---> prevents cross linking of PG
Mechanism of linezolid Binds 23s rRNA near P site. Competitive inhibitor of A and P substrate....Block initiation complex from forming
Mechanis of linezolid resistance mutation of 23s rDNA
Mechanism of resistance in TB Point mutations in drug targets (ie katG/inhA for isoniazid. rpoB for rifampin and GYRA for quinolones
By what method to Streptococcus and neisseria become resistant to drugs? homologous recombination of B-lactam-resistant PBPs (mosaics)
What compliment is responsable for opsonization? c3b
What compliments are the anaphylotoxins? C3a and C5a
The deposition of thrombi in small veseels with consequent damge to the areas deprived of blood supply is know as _____? What is its bacterial cause? DIC. Can be caused by endotoxic shock
Endotoxin ativates what clotting factor? XII (12) (hageman factor)
How does endotoxin trigger the series of "alarm reactions" that fend of the bacteria? Endotoxin binding to TLRs on macrophages
Thickening of the cell wall is seen in what bacteria's resistance to what antibiotic? Intermediate vancomysine resistance in staph
What is the mechanism of resistance for ALL aminoglycosides (ie; gentimycin) acquisition of a gene that allow for the modificaton of a drug via adenylation, etc.
Etest vs kirby-bauer Etest is performed using a plastic strip rather than a paper disk. It is better suited for bulky antibiotics (like VANCOMYCIN) which don't diffuse well from the paper. Etest is more precise
Example of a drug in which Etest would be good to use for suscepability testing? Vancomycin. or any other large, hydrophobic molecules
How is an Etest measurement interpretted when looking up on a standardized 2-fold dilution table? ROUND UP to to next two fold dilution on table!
What do the numbers on the Etest strip represent? The minimum inhibitory concentration (MIC) of the drug for the bacteria
Using microwell plates... how is the MIC determined? The well in which there is NO growth
What bacteria is RT-PCR currently used for? Vanc. resistant MRSA
A mutation in parC would cause resistance to what ABx FQs
L22 mutation (large subunit) would cause resistance to what ABx macrolides
What are the criteria for a nosocomial infxon? Infecion must have occured over (>) 48 hours after admission or within (<) 48 hours of discharge
HCA, HAI, CI HCA= health care acquired infection, HAI= hospital acquired, CI = community acquired
a c. diff infxon is an example of what type of infxon acquisition? iatrogenic
A sick doctor who passes illness on to pt, is an example of what type of infection acquisition? Iatrogenic
What is an indogenous infxon? Give an example An infxon that comes from within the patient from the normal microbiota, ie; s. aureus infxon from a nasal cavity.
What is an exogenous infxon? An infxon from an outside source. ie; healthcare working, etc.
Give examples of oppurtunistic infxons... E. coli, P. aeruginosa, Enterococcus faecalis/faecium, Klebsiella, S. aureus, the pneumonias
Major cause of UTIs (bacteria) E. coli (proteus vulgaris / meribelis as well)
Positive pressure rooms are used for what kind of pt? Immunocomp'd pt. These rooms do not allow any outside air to come in. (ie; burn victim, kidney xplant, etc)
Negative pressure rooms are used for what kind of pt? Pt with an aerosolizable disease (ie; TB, etc). These rooms do not allow any air inside the room to come out?
H antigen is:? K antige is? H antigen is flagellum type. and K antigen is capsule type
When comparing autoclave to dry heat, which uses a lower temperature? Autoclaves. Autoclave temp can sterilize at a lower temp (appx 120 degrees) because it does it at a higher pressure
disinfection vs sterilization Sterilization kills everything, including spores. Where as disinfection kills MOST organisms, NOT necesarily including spores
Minimum level of disinfectant to kill mycobacterium and viruses and all fungi. Intermediate disinfection
Give three examples of intermediate disinfectants alcohol, iodophore, phenolics
Alcohol is an example of what type of disinfectant (what level) intermediate disinfectant. Also an antiseptic
a quarternary ammonium compound will provide what level of disinfectant low level
What is the only antiseptic that can kill mycobacteria betadine
What is an antiseptic (definition) A type of disinfectant that can be used on live tissue. Alcohols, iodophore, betadine, chlorhexadine
Surfactants have what effect on microbes Usually does not kill them, just removes them. Sometimes more effective at disinfecting than alcohol (spores are not sensitive to alcohol, but can be removed with soap)
Aside from sterilizing, what is the most effective means of removing spores soap + water
Formaldehyde is what kind of agent (sterilant, disinfectant, etc?) sterilant. Kills everything, spores included.
Formaldehyde works through what mechanism? Alkylation / cross linking
Phenols work via what mechanism Membrane leakage... causes leakage through mitochondrial membrane, disrupting the proton gradient and preventing ATP production
Example of an organism that commonly has an efflux pump for disinfectants P. aeruginosa. It can grow inside of a disinfectant solution!
Created by: rkirchoff



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