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51 Cards in this Set
- Front
- Back
upper respiratory tract infections
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- common cold viruses (adenoviruses, non-SARS coronaviruses and rhinoviruses)
- replicate in epi surface of nasal mucosa - primarily in columnar and ciliated epi cells |
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lower respiratory tract infections
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- paramyxoviruses (parainfluenza virus, respiratory syncytial virus, and human metapneumovirus
- myxoviruses (influenza) - SARS(severe acute resp synd)- coronavirus - primarily cuase bronchitis, acute laryngotracheobronchitis (croup), bronchiolitis and pneumonia |
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The Common Cold
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- acute resp illness
- mild and self-limited - inflam of the Mucous Membranes of the nasopharynx (catarrh) - watery nasal discharge (which may contain sloughed columnar epithelial cells) - no fever - from rhinoviruses (100+ antigenic types) or coronaviruses (2) |
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Pharyngitis
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- acute inflammatory of pharynx
- sore and scratchy throat - edema and hyperemia of tonsils and pharyngeal Mucous Mems - from rhinoviruses usually(may involve variety of viruses) |
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Laryngitis
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- inflam of larynx MMs
- w/ common cold and influenza - lowering of the normal pitch, hoarseness, aphonia - from influenza, sometimes rhinoviruses, adenoviruses and parainfluenza viruses |
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Laryngotracheobronchitis
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- croup
- acute, involving the larynx, trachea and bronchi - kids under four - high fever and blockage of the larynx and perhaps bronchi - dyspnea and creaking notes - typically due to one of the parainfluenza viruses(maybe others) |
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bronchitis
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- inflam of tracheobronchial tree
- ass. w/ generalized resp infection - hyperemic and edematous MM ⇒ increased bronchial secretions - cough to clear them - destruction of epi(minimal->severe) - accompanys a variety |
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Bronchiolitis
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- acute inflam and necrosis of the bronchiole epi
- before the age 2 - acute onset of wheezing and hyperaeration, tachypnea and resp distress - from resp syncitial virus |
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Pneumonia
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- inflammation of the lungs
- 6th death cause in US - destruction of ciliated epi - diffuse congestion of alveoli w/ erythrocytes - fluid may be seen - from RSV and parainfluenza viruses in children - influenza viruses in adults |
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Adenoviruses Structure and Replication
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- naked icosahedral particles
- linear dsDNA - several dozen serotypes, divided into subgroups (A-F) based on antigenicity/RBC agglutinatation ability |
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Adenoviruses pathogenesis
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- genes E1A and E1B mediate transformation by deregulating cell cycle control by interacting w/ pRB gene
- not linked to human cancers - can maintain a long-term ass. w/ host by persisting in lymphocytes for years - discovered accidentally in cultured uninfected adenoidal tissue, from absence of immune surveillanc |
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Adenoviruses clinical features
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- can infect and replicate in:
1)RT 2)eye 3)GI 4)bladder 5)liver - 5-10% of acute RI in kids - also causes acute resp disease(ARD), a syndrome from fatigue and crowding among young military recruits |
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Adenoviruses Epi
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- worldwide
- sporadic to epidemic - mostly fecal/oral in kids, but can occur via the resp route |
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Adenoviruses vaccine
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- vaccines to prevent disease by certain adenovirus types
- vaccination -> asymptomatic virus replication in GI - not for civilians - concerns for spread of non-attenuated virus and oncogenic potential |
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Rhinovirus Structure and replication
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- (+) polarity ssRNA
- naked icosahedral capsid - capsid from copies of 4 proteins, like picornavirus - 30-40% of winter colds - replication T sensitive at 37° -> limits to URT(T<37) |
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Coronavirus Structure
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- (+) polarity ssRNA
- helical nucleocapsid - w/ envelope containing 3 or 4 glycoproteins in spikes - pleomorphic shape - 20-30% of winter colds |
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Rhinovirus and Coronavirus pathogenesis
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- confined to URT
- minimal and self-limiting - may set stage for more serious bacterial infections (sinusitis, Otitis Media) - only coronavirus can cause more serious disease in kids like bronchiolitis, bronchitis and pneumonia |
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Rhinovirus and Coronavirus Immunity
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- strain specific immunity after infection
- lots of serotypes (over 100 r) - c immunity limited - can be re-infected w/in 2 years w/ same strain -Long-Term immun to either is unusual |
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Rhinovirus and Coronavirus Epi
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- nose->hand->nose b/t people
- r can survive for hours on environmental surfaces(fomites-cups, doorknobs, etc.) - reducing spread via handwashing, ventilation, disposal of tissues - Chilling/cold-exposure are NOT responsible |
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Rhinovirus and Coronavirus Treatment
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1) Capsid-binding antiviral agents (WIN compounds) prevent virus binding and entry for R
- specifically bind a canyon - not effective against other comm cold(coronav./adenov.) - hard to administer to nasal mucosa 2) Anti-receptor compounds (ab's) against ICAM-1 - prevent R binding and entry - prevents, doesn't treat - adding soluble ICAM-1 receptor helps - resistant mutants rapidly evolve 3)complications - hard to treat b/c no early clinical recognition, no rapid differentiation, short half-life, poor biodistribution |
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Preventing Common Cold
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- no vaccine(b/c of lots of serotypes)
- disinfectants - handwashing(esp. staff of daycare/school/hospitals) |
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Respiratory Syncytial Virus Structure
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- irregular shape virions
- (-) sense ssRNA - helical nucleocapsid w/ envelope (3 spiky glycoproteins-virus specific) |
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Respiratory Syncytial Virus Replication
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- G glycoprotein binding initiated infection
- penetrates via envelope fusion w/ PM By F glycoprot - F mediates syncytium formation associated w/ infection - all events for replication in cytoplasm - transcribed by virion associated polymerase into Several mRNA's - nucleocapsids bud through PM - Replicates in wide variety of human/animal cells in culture |
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Respiratory Syncytial Virus Clinical Features
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- 4 to 5 day incubation
- 6-10 day recovery for kids - <1% mortality unless immunocompromised(may be fatal) - bronchiolitis characterized by lymph infiltration & edema - pneumonia characterized by audible rales or consolidation=infiltrates on x-ray - no deepter than superficial layers of resp epi |
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Respiratory Syncytial Virus Immunity
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- protection/recovery = mediated by secretory Abs, serum Abs and cytotoxic T
- get maternal Abs->low level of protection/infants produce low level of neutralizing Abs - diminished response of infants from immune immaturity or suppresive effect of maternal Ab or both - multiple re-infections does immunity in older children - secretory neutralizing IgA Abs better on nasal mucosa than serum, but not great - cellular immunity ok, but short-lived - local immunity most important in URT, serum Ab best in LRT |
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Respiratory Syncytial Virus Epi
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- severe in infants and kids, mild URT in adults
- infants(2-7 mo/premies)=esp prone to severe LRT-> bronchiolitis and pneumonia - most important viral thing in infants - big in immunosuppressed adults and elderly - all infected by age 2, adult re-infection common - 1o infection most severe - subsequent infections are symptomatic but penetrate less deep into RT |
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Respiratory Syncytial Virus Transmition
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- transmitted by close contact
- aerosolized in large droplets of resp secretions - infected kids shed for 3 wks - can stay of surfaces for hrs - spread in hospitals and daycare is a major problem - mid-winter to late spring - handwashing prevents! |
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Respiratory Syncytial Virus treatment
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- treat severe kids w/
1) humidified O2 2) bronchodilators 3) assisted ventilation 4) Ribavirin(as aerosol)-not very effective -RSV Prophylaxis 1) IV IG in high risk cases 2) no vaccines, but live attenuated being tested 3) hard to make infant vaccine b/c of maternal antibody and the immune immaturity |
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Parainfluenza Virus Structure
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- hPIV1-hPIV4
- (-) sense ssRNA - virion-associated RNA polymerase |
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Parainfluenza Virus Replication
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- replicates in cytoplasm
- encode a hemagglutinin / neuraminidase (HN) glycoprotein spike that binds sialic acid to attach and enter - high [sialic acid] in URT and LRT - viral genome transcribed(several mRNA's) and nucleocapsids assemble in cytoplasm and bud through PM - encodes an (F) spike and forms syncytia |
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Parainfluenza epidemiology
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- throughout world
- often nosocomial - transmition=person to person contact or spread of contaminated secretions - Shed for 4-7 days after inf(sometimes longer) - re-inf w/ same hPIV can occur(illness is less severe) - 1o inf of hPIV1/2=kids >2(probably maternal Ab protect against sever) - most kids have hPIV3 Ab w/in 1yr - hPIV1/2=biannual epidemics(autumn, though strains may be endemic for several years) - hPIV3 inf tend to be endemic throughout year |
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Parainfluenza Virus Clinical features
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- 2nd cause of LRT in kids
- the most common cause of laryngotracheobronchitis(croup) in kids (esp type 1) - non-croup infections present as a hoarse cough w/ fever which resolves in 2-3 days |
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Parainfluenza Virus Immunity
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- nasal secretory IgA Abs better than serum Abs
- only Abs to HN and F have been shown to neutralize virus |
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Parainfluenza Virus Pathology
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- gets epi of the pharyngeal and nasal mucosa
- spread from cell to cell by fusion then spread to the epi of the larynx and trachea - resulting inflam -> croup - restriction to RT b/c host cell proteases cleave the viral fusion protein - w/out this, virions cant infect other cells |
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parainfluenza prevention
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- inactivated vaccines fail(b/c of importance of local secretory IgA Ab)
- subunit vaccine(w/ HN and F)=partially effective, but may help live attenuated virus vaccine - kids vaccinated w/ bovine PIV3 are protected from hPIV3 - lots of attenuated mutants of hPIV3 developed(need to correct problems w/ reversion to wild type) |
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parainfluenza treatment
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- humidification by ultrasonic nebulizer
- periodic inhalation of racemic epinephrine(somewhat successful) - inhaled steroids or systemic corticosteroids(somewhat effective at lessening severity of symptoms) - No anti-viral therapy yet |
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Influenza Structure
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- pleomorphic virions
- smaller than paramyxoviruses - 8 segments of (-) polarity ssRNA - segments individually wrapped into helical nucleocapsids by Nucleoprot(NP) w/ envelope - viral RNA polymerase is packaged within the virion - 2 proteins on surface, hemagglutinin (H) and the neuraminidase (N) - first identifies as H1N1(re-surfaced '77), but H2N2(asian flu '57) and H3N2(hong kong flu '68) also came along (so H1N1 gets people born after '57 b/c older have immunity |
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Influenza C
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- infects humans and swine
- causes sporadic URT illness, rarely LRT disease - least severe |
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Influenza A
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- in both humans and animals
- most severe |
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Influenza glycoprotiens
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HA:
-entry into host cell mediated by HA binding to sialic acid -HA cleaved->2 peptides by extracell proteases(required for uncoating) - cleavage blocked/altered by mut->virulence=greately reduced - easier to cleave=more virulent - Ab to HA blocks virus inf-prevents clinical illness NA: -cleaves sialic acid residues->facilitate cell-cell spread(by releasing virus from secretions and infected cells) - Ab to NA limits spread-lessens clinical disease |
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Influenza B
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- only human, preferentially kids
- Reye's syndrome is a complication w/ aspirn instead of acetaminophen for fever - HA and NA relatively stable, genetically |
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Influenza Replication
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- replication in nucleus
- virus polymerase error prone(lack of proofreading, mutation at freq of 10^-4/-5 per nucleotide per inf cycle) - individual nucleocapsids encapsidate each segment, then they assemble at random into virions and bud from PM - as many as 12-15 incorporated to ensure that all 8 required segments are there - if 2 different strains replicate in same cell -> reassortment and new combos(by RNA reassortment) (esp w/ A, no reassort b/w abc) – bad!!-most rapidly evolving virus in nature |
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Influenza Clinical Features
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- 3-5 day recovery(fatigue/depression may persist), some may develop pneumonia (will be what kills you)
- asymptomatic to fatal primary influenza(worse in kids/old/already debilitated) - clinical onset occurs with a sudden rise in temperature within 1- 4 days post-exposure - correlation b/t level shedding and severity(most self-limiting=several days) - coughing possibly for months after clearing, as ciliated epi is re-established - lots of other symptoms, NO such thing as "stomach flu" |
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Influenza Pathogenesis
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- Spread via inhaled aerosol drops(sneezes/coughs)
-deposited on tracheobronchial tree, replication is initiated in all superficial cells of RT - replication -> desquamation of ciliated epi(common acute symptoms-sore throat, substernal pain, SOB, nonprod cough) |
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Influenza Epidemiology
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- great unconquered epidemic
- antigenic drift/shift - Influenza A evolution->new vaccines need to be made regularly - new strains spread rapidly in kids and crowded areas - epidemics cause economically significant absenteeism |
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Influenza Pandemic
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- excess mortality
- results from novel A virus - 1918, 1957 and 1968. - confined mainly to elderly and ill |
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Influenza Treatment
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1)Supportive treatment for relief of symptoms, does NOT shorten duration or lessen complications
- acetaminophen instead of aspirin reduces risk of Reye’s syndrome from B 2)Anti-Viral Drugs (amantadine or rimantadine) - inhibits viral uncoating – gets A if given w/in 48 hrs, NO effect on B or H5N1 – shortens: course by 1-4days, period of reduced pulmonry function - reduces: sympt severity, titer and duration of viral excretion 3)Neuraminidase Inhibitors (A and B) - binds sialic acid binding site on NA->blocks replication and symptoms - non-toxic, available soon 4)Prevention - prophylactic amantadine (for A only) - effective against all H1,H2,H3 virus isolates - side effect, must be taken throughout period of risk |
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Influenza Vaccines
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1)Currently: formaldehyde-inactivated virions from embryonated eggs(allergic to eggs=no vaccine)
- 2 doses (1month interval) for non-immunized kids, 1 dose for adults - induces anti-HA Ab(from most recent A and B) in 85% - immunity short lived(6-12mo) - WHO network monitors and detects new viruses - vaccinate old, infants, chronic disorders, and pregnant 2)Others: - Trivalent vaccine for 2004 - 2005 - FluMist™ - cold-adapted, live-attenuated, trivalent(inhalation) - Molecular vaccines a)appropriate HA Ags in genetically engineered bacteria and live attenuated A and B chimeric viruses |
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influenza complications
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1)2o bacterial infections
- lose normal mech for clearance of bact-> increases 2o bact pneumonia - esp in old, smokers, chronic bronchitis, other pulm func deficits - common orgs=strep pneumo, staph sp., Haemophilus infl 2)1o viral pneumonia is less common - usually old or CP disease - hypoxema and death w/in 1-4 days 3)Reye’s syndrome - cerebral edema / fatty degen of liver - in kids w/ B - high fatality - 3-way connection w/ ingestion of salicylates(aspirin) - 300+ cases of Reye's in US during 73-74 infl B epidemic 4)2 other specific CNS syndromes |
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Influenza Antigenic drift
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1)Antigenic Drift
- high mutation rate (since RNA pol error, lack proofread enzymes) - HA Ab correlated with protection against disease - antigenic changes in HA protein -> new strains that can escape neutralizing Ab(unrecognized by Ab) - antigenically new strains every 2-3 years->people can be re-infected, endemic/epidemic outbreaks |
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Influenza Antigenic Shift
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2)Antigenic Shift-3 factors:
– (1) in A zoonotic allows reservoirs(birds,horses,swine) for propagation of viruses, more H and N possibilities(3H's/2N's in humans, but: 15H's, 8N's in birds->H5N1 in hong kong killed 5) – (2) individual cells may be infected w/ different virus strains – (3) segmented nature of genome - Result: random recombination of RNA from diff strains/species(places where people/birds/swine are close(asia) have new pandemics) |