Term
| what kind of virus is influenza? |
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Definition
| part of the orthomyxoviridae family, influenze is a *segmented (different genes on different pieces - important when making vaccines, b/c can pull segments from diff. viruses) negative stranded RNA enveloped (subject to drying) virus inside a helical nucleocapsid. it is classified into 3 genera: A (most of the antigenic variation),B (doesn't cause the flu as often, used in vaccines),C |
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Term
| what are 2 imporant surface proteins for influenza? |
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Definition
| hemagluttinin (HA): responsible for attachment and fusion, neuraminidase (NA): cleaves sialic acid |
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Term
| what is the M2 protein found in influenza? |
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Definition
| M2 is a viral ion channel protein in the envelope, which is targeted by anti-virals |
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Term
| what is the influenza matrix protein involved in? |
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Definition
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Term
| about how many segments does the influenza A genome have? |
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Definition
| ~8 - for a viable virus, need copy of each one incorporated into the viral core |
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Term
| what are the influenza A,B,C subgroups based on? what are the subtypes of influenza A based on? |
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Definition
| influenza A,B,C subgroups: the antigenicity of the nuclear (NP) and matrix protein (M) antigens. subtypes of influenza A: hemagglutinin (HA - 16 types) and neuraminidase (NA - 9 types) |
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Term
| what are influenza A subtypes of note? |
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Definition
| currently circulating human strains (seasonal flu): H1N1, H1N2, H3N2. avian strain: H5N1. 2009/swine flu: H1N1 (different than the human H1N1) |
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Term
| when does the normal flu season start? |
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Definition
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Term
| what is the function of influenza surface protein hemagglutinin (HA)? |
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Definition
| HA attaches to sialic acid residues and mediates virus/cell fusion - which requires cleavage of HA by cellular proteases and low pH-mediated conformational change in HA. once HA binds, it is incorporated into an endosome (which is acidified), there is fusion between the viral envelope and endosome membrane, and then the genome is released into the cell |
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Term
| is there a difference between human/avian HA function? |
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Definition
| human HA binds SA-alpha-2,6 Gal-terminated saccharides and avian HA binds SA-alpha-2,3 Gal-terminated saccharides |
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Term
| what does influenza neuraminidase (NA) do? |
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Definition
| NA cleaves sialic acid residues - which promotes spread by aiding in budding/release of virus from the cells, and cleaved sialic residues in mucus - prevents mucus from inhibiting binding |
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Term
| what does influenza M2 protein do? |
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Definition
| this ion channel is important in entry as it allows H+ into the viral core once the endosome is acidified. low pH promotes dissociation of the nucleocapsid protein and the viral genome |
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Term
| what are the two antivirals for influenza related to the M2 protein? what forms of influenza does this work on? can influenza develop resistance to them? |
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Definition
| *amantidine and *rimantidine, which inhibit the M2 ion channel protein, and thus interfere with w/uncoating. these only work against Flu A (B doesn't have M2) and resistance is seen in H2N2/2009 H1N1 via mutations in M2 |
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Term
| what are the two antivirals for influenza related to NA? what forms of influenza does this work on? can influenza develop resistance to them? |
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Definition
| *zanamivir and *oseltamivir are both NA inhibitors and active against influenza types A and B. most seasonal H1N1 subtypes in the US are resistant to oseltamir, but sensitive to zanamivir |
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Term
| what is the best way to prevent influenza? |
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Definition
| vaccine (will still be dependent on host's ability to produce antibody response) |
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Term
| when are antivirals used against influenza? |
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Definition
| prophylaxis, (not meant to replace vaccine, but stand in until an at-risk group is vaccinated), lessening symptom severity (if given w/in 1-2 days of onset of symptoms), if the infected pt already has a severe illness, and if people have had contact with swine-flu infected pts (use zanamivir if type is not known, seems to have the least resistance) |
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Term
| in terms of influenza A, what is antigenic drift? |
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Definition
| *point mutations in the HA or NA glycoproteins, resulting in epidemics b/c the population may have cross reactive antibodies providing partial immunity |
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Term
| in terms of influenza A, what is antigenic shift? |
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Definition
| a *major antigenic change due to reassortment of HA and/or NA glycoprotiens, responsible for serious epidemics and pandemics b/c the population has little or no protective immunity |
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Term
| what is the theory for how antigenic shift occurs? |
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Definition
| birds and humans do not have the same sialic acid, so their types of HA/NA do not usually mix genetics - however pigs have epithelial cells that express the kind of sialic acid found in both avian and human strains, so it is thought that reassortment of avian/swine/human strains happens in pigs and then humans are reinfected. there is also a need for adaptation in human cells in order to replicate more efficiently. mutations may happen in pigs and reassortment may happen in humans as well. |
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Term
| if only one of the glycoproteins expressed on an influenza virus mutates, but the other remains the same - is there partial protection from the immune system? |
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Definition
| yes, and HA antibody provides stronger protection than NA antibody does (b/c better at neutralizing influenza) |
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Term
| what prevents the avian flu from becoming a pandemic? |
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Definition
| the avian flu is a strain of bird-originated influenza that can infect humans, but it is not transmitted human-to-human, and this prevents it from becoming a pandemic strain |
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Term
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Definition
| a swine strain circulating in humans |
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Term
| what is the 2009 H1N1? what made it become pandemic so easily? |
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Definition
| not the same as the seasonal human H1N1, b/c it is a swine strain. therefore, unless people were already exposed to it last year, everyone this year will also be susceptible. it is a reassortment virus from swine influenza circulating in europe/asia/north america (swine/avian/human combo). it is not present in pigs, but they can get it from humans. it is *very easily transmitted from person-to-person and *people do not do not have prior immunity = why it became pandemic. it also seemed to affect a younger population (older population may have had some cross-reactive antibodies) |
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Term
| how severe of an illness does the 2009 H1N1 cause? |
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Definition
| it is very contagious, but only causes a relatively mild illness |
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Term
| what is the clinical presentation of a pt infected with 2009 H1N1? |
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Definition
| incubation 1-4 days, symptoms: fever, headache, malaise, sore throat, nasal discharge, dry/nonproductive cough, GI symptoms, otitis media, croup (children) - similar to seasonal flu |
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Term
| what can a seasonal/2009 influenza infection result in? |
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Definition
| a secondary bacterial infection or a viral pneumonia |
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Term
| what is the background for avian flu? |
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Definition
| an H5 influenza w/subtype H5 killed a lot of chickens in 1997, a 3 yr old boy died as a result of this flu and reye's syndrome, then 18 more people died. it seemed to be transmitted from bird -> people, not person -> person. hong kong then killed all their chickens to stop the spread. it then re-emerged in 2003 as a more virulent flu |
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Term
| what is the current status of the avian flu? |
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Definition
| H5N1 has become endemic in some areas and will continue to infect some people via bird->person (person->person continues to be rare and never beyond one person). H5N1 shows some resistance to amantadine/rimantadine, but oseltamivir/zanamivir still appear to be effective. the current H5N1 seems more pathogenic in mammals than seen in earlier H5N1 viruses |
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Term
| how could the H5N1 cause a pandemic? |
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Definition
| yes if there were point mutations that allowed the AI/H5 to bind to SA-alpha-2,6 gal-terminated saccharides. there may also be changes needed in viral replication polymerase and other replication proteins for full adaptation to mammalian cells to occur. if all of these mutations did happen, most people would be susceptible due to a lack of prior immunity to the H5 subtype. |
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Term
| what characterizes the clinical disease due to the avian (H5N1 flu)? |
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Definition
| incubation period 2-8 days (longer) and symptoms include watery diarrhea w/o blood, hoarseness, crackling and difficulty in breathing after 5 days, sometimes bloody sputum, and multiorgan disfunction: esp the kidney and heart (more likely to disseminated, HA can get cleaved in more places in the body). almost all pts develop viral pneumonia, clinical deterioration is rapid, and 50% of lab-confirmed cases have been fatal. also not all confirmed pts have presented w/respiratory symptoms |
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Term
| what does the current influenza vaccine protect against? how are they generated? |
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Definition
| the most prevalent circulating strains: 2009 H1N1, seasonal flu (H3N2, H1N1, influenza B) - which is updated annually based on the antigenicity of circulating strains. the vaccine strains are generated by reassortment between lab-adapted strains and viruses closely related to the currently circulating ones - takes advantage of the fact that the genome is segmemented |
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Term
| what is the recommended composition of the 2010-2011 vaccine? |
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Definition
| 2009 H1N1, H3N1, and influenza B |
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Term
| what are the 2 forms of vaccines? |
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Definition
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Term
| what is the inactivated flu vaccine? |
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Definition
| this is grown in eggs (caution w/egg allergies), and is formaldehyde inactivated. it consists of 6 of the segments from laboratory strain and 2 from circulating A and B viruses (HA and NA). it is given to children older than 6 mos and adults over 65 |
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Term
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Definition
| a live attenuated cold-adapted virus that is delivered as a nasal mist and is approved for pts between 2 and 49. it is also made from 6 protein genes from cold-adapted strain and HA and NA from circulating virus |
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Term
| can the avian flu vaccine that was produced in 2007 still help create some antibody response in people even if the antigenicity of a proposed pandemic is different? |
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Definition
| yes, though there is major concern of a reassortment of the vaccine viruse with a circulating avian flu virus |
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Term
| who should be targeted for influenza vaccines? |
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Definition
| young children, the elderly, people in nursin homes/long term care facilities, pregnant women people with underlying chronic conditions, people on ASA therapy (avoid reye's syndrome), and people that can transmit disease to high risk pts |
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