Resp Viruses

Question 1

Resp Tract Broken Down

Answer 1

• _Upper Resp: _
• Nose (mouth)
• Throat
• Epiglottis
• Larynx
• Middle ear & paranasal sinus
• Lower resp:
• Trachea
• Brochi
• Bronchioles
• Alveoli
• Deaths by resp infections #1 among low income populations

Question 2

Defense against infections

Answer 2

• Nose: Hair, cilia, turbinates or nasal concha/mucus filter dust & particles = Sneezing
• Change in direction: airway from sinuses to pharynx deposits particles @ **back of throat **
• Lymphoid tissue:
• Adenoid gland: Between nose & throat @ end of soft palate
• Tonsils: Both sides of pharynx
• Trachea: layer of mucus & ciliated cells=Coughing
• Resp secretions: Lysozyme ^{(gram+ bacterial cell walls)}, IgA, lactoferrin, mucus
• Alveolar macrophages: Lower resp tract
• Normal flora: upper resp tract

Question 3

How Pathogens avoid immune defense

Answer 3

• Avoid mucus = NOT being expelled out
• Avoid phagocytosis & multiply/divide in phagocytic cell
• Major virulence factors(mol secreted by pathogens):
• Bacterial adherence-surface structures
• Extracellular toxins-Cytoxins
• Growth in host tissue-intracellular
• Evasion of hose defense:
  
  • Capsules-multiple types
  • Production of IgA proteases
• TB avoiding immune defense w/granuloma
• Multiple strains of strep (94)

Question 4

Syndromes of Upper Resp

Answer 4

• Defense = Normal Flora
• Common cold
• Pharyngitis
• Influenza
• Diphtheria
• Sinusitis & Otitis Media
• Rhinocerebral mucrormyosis
  
  • **Effects immunocomprimised **
• Epiglottis
• Croup/laryngitis

Question 5

Syndromes of Lower Resp

Answer 5

• Defense: Macrophages
• Whooping cough
• Bronchitis/Brochiolitis
• Influenza
• Pneumonias
• Typical
• Atypical (walking) develops from bacteria, viruses, fungi not common typical (chlamydo, mycoplasma, legionella)
• Community/Nosocomial (hospital)
• Occupational-Bacillus anthracis/Chlamydophila psi
• Regional
• Opportunisitc-Aspergillus spp/pneumocystis Jiro
• Pulm TB = Myobacterium TB

Question 6

Etiologic Agents of Resp Infections

Answer 6

• Microbal toxins that cause disease-Viruses, bacteria, fungi, Protozoan(unicellular), Helminthes
• Viruses more common
• Bacterial infection more serious=life threatening diseases
• Many of upper resp tract pathogens ALSO cause lower resp tract infections
• Influenza can effect BOTH lower/upper
• Vocal cords are a marker for upper & lower resp tract
• Bacteria:
• Staph aureus-major cause of pneumonias
• Francisella tularensis-gram(-) lethal cases of pneumonias
• Coxiella burnetti-Gram(-) bio weapon

Question 7

Common Cold

Answer 7

• Acute viral infection of resp tract w/inflammation in some or ALL airways (nose, paranasal, throat, middle ear, larynx)
• Symptoms:
• Nasal discharge & obstruction
• Sneezing
• Sore/scratchy throat
• Cough
• Chilly sensation w/slight fever
• Etiology: Multiple agents 90% viral
• Rhinovirus (common)
• Coronavirus (SARS-10-15%)
• Influenza (25-30%)
• Adenovirus (5-10%)
• Also less common chlamydia
• Human Metapneumoviruses (influenza)
• Complications: Sinusitis & otitis media Both Viral/Bacteriral w/asthma
• Treat w/1st gen anti-histamines or NSAID

Question 8

Pharyngitis

Answer 8

• Divided into Naso, Oro, Laryngo (top-bottom)
• More common in children & @ winter time
• Symptoms: “Sore throat”
• Dysphagia (pain w/swallowing)
• Fever & headache
• Enlarged lymphnodes(neck)
• Occasional runny nose/post nasal drip
  
  • Pus or no pus
• Etioloic agents:
• Adenovirus
• Coxsackie
• Epstein Barr ^(mono)
• Strep pyogenes
• Corynebacterium Diph ^{<u><strong>(mycobacterium)</strong></u>}

Question 9

Sinusitis & otits media

Answer 9

• Occurs after viral infections
• Sinusitis: Inflammation & obstruction of sinuses due to pus_(may follow tootch extraction due to normal flora)_
• Fever-headache
• Thick colored post nasal discharge
• Halitosis
• Otitis media: Inflammation & obstruction of middle ear due to pus behind tympanic(NOT present in viral)-sharp pain w/hearing loss, vomiting (anorexia)
• Pathogens:
• Strep pneumoniae ^{(normal flora)}
• Haemophilus influenzae ^{(normal flora)}
• Moraxaella catarrhalis ^{<strong>(common)</strong>}
  
  • gram(-) aerobic
• Pseudomonas aeruginosa ^{<strong>(common)</strong>}
  
  • Immunocomprimised

Question 10

Croup: Laryngotracheobronchitis

Answer 10

• Area between pharynx/trachea contains vocal cords w/mucous membrane
• Symptoms: Resp obstruction swelling
• Follows upper resp infection
• Breathing diff, hoarseness w/Seal’s bark cough, Inspiratory stridor (high pitched-vibrating)
• Gets worse laying down
• High risk in 3 months-5 years
• Exam: Restrictions on breathing, PROLONGED inspiration/expiration, wheezing
• Sucking in of skin on inhalation-increased use of chest wall muscles
• X-ray-Steeple sign ^{(narrowing of upper trachea)}
• Etiology: Parainfluenza virus (80%), RSV, measles, adeno, influenza

Question 11

Bronchitis/Bronchiolitis

Answer 11

• Inflammation of bronchial tubes-occurs after upper resp
• Symptoms:
• Fever, cough, & sputum production
• Sore throat
• Runny or stuffy nose
• Headache
• Muscle aches & extreme fatigue
• Etiology: Virus & bacteria
• RSV (syncytial-COMMON)
• Parainfluenza/Influenza
• Mycoplasma pneumon
• Chlamydophilia (community)

Question 12

Pneumonias Classification

Answer 12

• Infection of alveoli or walls
• Could involve interstital ^{(between alveoli)}
• Classification:
• Location-Community or nosocomial
• Oset-typical (acute), atypical (gradual), Chronic
• Site affected- lobular, multilobular, broncho, interstitial
• Regional- found only certain areas
• Occupational-zoonotic ^{<strong>(cross species)</strong>}
• Aspiration-Normal flora from Upper

Question 13

Symptoms of Pneumonia

Answer 13

• Typical: rapid onset, high fever/chills, dyspnea, productive cough (blood), wheezes/cracks
  
  • X-ray: Dense consolidation
• Atypical: moderate onset, low fever/chills, sudden attack cough w/moderate sputum
  
  • X-ray: Vague-patchy consolidation
• Chronic: Gradual onset, night sweats, low grade fever, weight loss w/productive cough

Question 14

RNA virus Rhino (Non-enveloped-Picornav fam)

Answer 14

• ss(+) RNA & 100 types known
• Replication in cytoplasm ^{RNA-dep/RNA poly}
• Reservior: Humans/Chimpanzees
• Transmission: Worldwide, seasonal(summer-fall), Direct contact, resistant to drying/Detergents
• Pathogensis: receptor on host ICAM-1
• Low infectious dose/Nose, eye, mouth
• Infected cells make-histamine/bradykinin
• Replicates @ 33C better for upper resp
• Acid labile-Killed in stomach
• Diagnosis: Rarely done
• Viral isolation-swabs saliva, nasal, pharyngeal
• Serology-confirm virus as infection & assessment of immune status
• Treatment: Hand washing w/NO vaccine due to so many serotypes

Question 15

RNA virus Corona (enveloped-Coronavir fam)

Answer 15

• Spikes on surface due to large glycoprotein=Looks like *corona/crown *
• (+) ssRNA virus replicated in cytoplasm w/RNA dependent RNA poly
• optimum temp 33-35C=Upper resp
• S protein for attachment coating itself resemmbling Fc-gamma receptors on immunoglobulins
• Reservior-Corona(Human)
• SARS-Cov(bats, cats, raccoon)
• MERS-NCOV(middle east bats, camels)-Immunocomprimised
• Transmission-Airborne droplets nasal or Oral-fecal (winter-spring)
• SARS-COV: kills alveolar cells w/diarrhea
• High fever, sore throat, ATYPICAL pneumonia, dyspnea
• RT-PCR w/ELISA Ab=Diagnosis
• Treat: Interferon-Ribavirin

Question 16

DNA virus (non-enveloped) Adenovirus life cycle

Answer 16

• Icosahedral shape w/hexon capsid proteins
• Peplomers: Pentons @ apices w/protuding fibers=attachment (HE)
  
  • Purified fibers toxic to human cells
• Reservoir: Humans w/asymptomatic shedding
• Receptors on host cells:
• CAR-Coxsackie: Glycoproteins in Ig super family ^{(CAR used by Coxsackie virus too)}
• CD46 (membrane co-factor protein)
• MHC class 1
• Integrin (internalization)
• Sialic acid (RBC & Upper resp)
• Endocytosis-Repication in nucleus
• Early protein synthesis FOLLOWED by replication THEN late protein synthesis

Question 17

DNA virus (non-enveloped) Adenovirus Pathogenesis

Answer 17

• Lytic: Permissive cells=host cell death
• Target cell-muco-epithelial cells in resp tract ^{(upper & lower)}, GI, Urinary
• Latent: non-permissive cells=recurrence in immuno comprimised pts
• Target cell-Infections in lymphoid cells ^{(tonsils, adenoid, peyer’s patches)}
• Transforming infection: Cancer @ the site on incoculation ^{<strong>(hamsters only)</strong>}
• Transmission: Close contact, aerosol, fecal-oral
• Resists dryness, deteregents, mild Cl- (survive up to 90 days in pools)
• High Risk: Children, crowded areas, SWIMMING clubs

Question 18

DNA virus (non-enveloped) Adenovirus Clinical

Answer 18

• Pharyngitis=1,2,3,5,7:
• Common cold symptoms
• Fever, Sore throat, Inflammed Pharynx
• Pharyngoconjunctival fever=3,7:
• Assoc w/pools
• Conjunctivitis, fever, vocal cord inflamm
• Acute resp disease=4,7,21:
• Military recruits
• 3rd week of training
• Fever, malaise, sore throat
• Sudden drop in O2 in blood
• Vaccine available (made of 4&7) oral & replicate in GI bypas resp
• Pneumonia=1,2,3,7:
• Mostly children and severe
• GI^(diarrhea)=40,41
• Diagnosis: Immunoassay fluorescent Ab or ELISA or PCR

Question 19

RNA virus Coxsackie (Non-eveloped Picornaviri)

Answer 19

• (+)ssRNA w/2 types A & B
• Reservoir: Humans
• Transmission: P to P, fecal-oral, Airborne
  
  • ^{Ex. Diaper changing stations}
• High risk: infants & young children in Summer/Fall seasons
• Treatment: COXA self-limiting (4-7days)
• No vaccines
• Prevention: Proper hygiene, boiling utensils
• Herpangina: Vesicular pharyngitis
• Sudden fever, headache, Sore throat, Dysphagia
• Ulceration/Rash in pharynx, tonsils, mouth
• Hand-foot-mouth: mild fever, vesicular lesion-hand, foot, mouth, tongue
• Caused by type COXA16

Question 20

DNA virus Herpes (enveloped) General

Answer 20

• Large w/linear dsDNA
• Lytic, persistant or latent transforming infections
• Vesciles seen in HSV1/2
• HSV 1=Cold sores-latent in trigenminal
• Grouped on what cell types they infect
• Alpha herpes(infect epi cells):
• Simplex (HSV-1 & 2)-Upper resp
• Zoster-varicella (HHV 3)
• Gamma herpes(infect vareity cells):
• Epstein-Barr (HHV4)
• Kaposi sarcoma (HHV8)
• Beta herpes(infect lymphoid cells):
• Cytomegalovirus (HHV5)-Upper resp

Question 21

DNA virus Herpes (enveloped) Epstein Barr

Answer 21

• ds linear DNA-Enveloped HHV4
• Asymptomatic shedding w/saliva w/lifelong infection
• Transmission-P to P saliva
• High risk-Young adults not infected ^{<strong>(mono)</strong>}
• Infections in infants (when maternal Ab stops) or early childhood life long immunity
• Cell infected = Epithelial (oro/Naso) & B-lymph
• Virual gp350 attaches to comp C3b receptor-CR2(CD-21)->Gp42->MHC2
• Permissive(productive): replicates/lysis of infected cells contain-
• Early Ag, Viral capsid Ag, Membrane Ag
• Non-permissive(latent):B cell mitogen ^{(uncontrolled prolif)} EBV DNA in nucleus, NOT integrated w/chromosome
• Epstein barr nuclear Ag & Latent membrane protein = Immortal growth

Question 22

DNA virus Herpes (enveloped) Epstein Barr Clinical

Answer 22

• Acute: Infectious Mono=Heterophile Ab (+) sheep blood agar ^{(paul-bunnel test)}
• Fever, Sore throat, Lymphadenopathy, Splenomegaly & FATIGUE 1-4 weeks
• Chronic: Recurrent-Fatigue, low grade fever, sore throat
• Ampicillin^{<strong>(beta-lactam)</strong>}rash seen in pts under treatment
• Additional diseases associated:
• Leukemia/Lymphoma-T-cell def or Immunosuppresed
• Burkitt’s-Tumor of Bcell, Jaw/face, Africa-malaria belt
• Nasopharyngeal carcinoma-Cancer of epi, Asia, genetic
• Oral Hairy leukopenia-AIDS pt, Wart like growth, multiplies in epi cells

Question 23

DNA virus Herpes (enveloped) Epstein Barr Diagnosis

Answer 23

• Incubation time 2 months or more
• Hematologic:
• Atypical T lympho (Downey cells)
• T cells are larger w/vacuolated cytoplasm & basophilc inclusions
• Serology:
• Heterophile Ab: non specific IgM Ab-Bind to paul-Bunnel Ag on horse, sheep RBC
  
  • Monospot test(horse)-quick
• EBV specific Ab test: IgM active infection against viral capsid Ag or Early Ag
  
  • IgG & AntiEBNA for chronic
• Treatment: Self-limiting or Steroids for controlling swelling

Question 24

RNA virus (enveloped) Paramyxoviridae

Answer 24

• (-) sense ssRNA & non-segemented
• Cytoplasmic replication
• Buds from plasma membrane
• 3 genera cause Resp tract infections
• Paramyxovirus: Parainfluenza/Mumps
• 2 spikes:
• F peplomer spike=fusion results in multinucleated cells (synctia)
• Posses spike=Hema & Neuraminidase
• Pneumovirus: Resp syncytial & Metapneumo
• Morbillivirus: Measles

Question 25

RNA virus (enveloped) Parainfluenza Clinical

Answer 25

* **_Transmission:_** inhalation of large droplet * **_High risk:_** Children 6mos-12yrs, short term immunity after disease * **_Pathogenesis:_** Inside epi cells-form giant cell & lysis * ***Adhesion mediated*** by Hemagglutnin-binds to sialic acid * ***Neuraminidase clips*** sialic acid for virus release * **_Clinical:_** Croup & Laryngotraceobronchitis * Mild cold-like upper resp infection * Can extend to larynx, trachea, & ***bronchial tree = CROUP*** or bronchiolitis & pneumonia * **_Croup=_**cough is sharp like seal's bark due to ***subglottal swelling=High pitch*** * ***X-ray steeple sign***

Question 26

RNA virus (enveloped) Parainfluenza diagnosis

Answer 26

* Best specimens are ***nasopharyngeal secretions*** * **_Ag detection:_** Immunofluorescence * **_Serology:_** Hemagglutination inhibition test, ELISA * **_Treatment:_** * ***Hospitalization-***Treat symptomatically & monitor airway continuosly * ***Cold or warm mist*** (humidirfier)-***Croup tent*** * O2-may have intubated due to narrowing of trachea * ***IM dexamethasone*** (corticosteroid) & inhaled epinephrine (pediatric) * NO vaccine & re-infections common

Question 27

RNA virus (enveloped) RSV General

Answer 27

* (-) ssRNA w/surface spikes only F protein (NO HG or Neuraminidases) * **_F protein:_** fusion multinucleated (syncytia) * **_Reservior_**: Humans ***everyone infected*** by age 3 * **_Subtype B:_** asymptomatic affect majority of population * **_Subtype A:_** More severe & ***dominant in most outbreaks*** * **_Transmission:_** Inhalation of large droplets-***Peaks in winter*** * **_High Risk:_** ***Premies-more severe*** w/lower resp=Brochiolitis * Common cause of ***acute FATAL resp tract*** infections * **_Adults:_** Mild symptoms, common-cold like. Very few infections are life threatening

Question 28

RNA virus (enveloped) RSV Pathogenesis

Answer 28

* Cause of ***fatal acute resp tract infection*** in infants * Infects epi cell & make giant cells & kills cells * Immuno mediated ***(CD-8)*** cell injury-***necrosis/sloughing of bronchiolar epi*** * ***Formation of plugs-***Mucus, fibrin, necrotic material obstructs airway=***Bronchiolits*** * More dangerous in infants due to ***smaller peripheral airways*** than adults * **_Symptoms:_** Mild Upper resp infection progress to cough-\>wheeze-\>dyspnea * Increased resp rate=***Tachypnea*** * Rales, fever-\>turns into ***Lower resp=Pneumonia*** * **_RSV sign:_** ***intercostal/substernal retraction*** * **_Long-term=_**Asthma & pulm deficits

Question 29

RNA virus (enveloped) RSV Diagnosis

Answer 29

* Ag detection assays (immuno)- * Cytophatic effect=***Multinucleated cells*** w/basophilic cytoplasmic inclusion bodies * **_Treatment:_** * ***Symptomatic-***Bronchodialators (metaproterenol/Albuterol) helps relieve chest congestion & wheezing * **Severe cases=**O2 therapy, Aerolized ***Ribavirin*** (analogue of guanosine) * **_Passive immunization:_** Hyperimmune globulin against RSV ***(Respigam)*** * **_Prevention:_** Infection for re-infection * ***Immuno-prophaylaxis-***Children under 2 who have chronic lung disease * Monoclonal Ab against F-protein***(palivizumab)***

Question 30

RNA virus (enveloped) Metapneumovirus

Answer 30

* ss(-) RNA from family paramyxoviridae * Recently recognized pathogen * Could cause ***15% of children's colds*** * **_Can cause:_** * Bronchitis (mucous membranes) * Bronchiolitis (small bronchioles) * Pneumonia * ***Very common-***children by age 5 are seropositive

Question 31

RNA virus (enveloped) Influenza-General

Answer 31

* ss(-)RNA & ***8 Segmented RNA*** * Replicates in nucleus^{(instead of cytoplasm)} * Has ***RNAdep-RNApoly*** * **_Matrix proteins important in uncoating:_** * ***HA (hemagglutinin)*** * Initiate by binding to sialic acid on epi cells * Agglutinates clumping-RBC * ***NA (neuraminidase)*** * Cuts sialic acid to release virus/dissolves mucus * Vaccines target these proteins ***(no binding=no infection)*** * 3 types based on variation of ***matrix proteins & nucleocaspid proteins*** (viral penetration into host nucleus)

Question 32

RNA virus (enveloped) Influenza-Life Cycle

Answer 32

1. ***HA sticks to sialic acid on host cell-***Virus enters by fusion into ***endosome*** (storage b4 nucleus) 2. Matrix proteins=uncoating 3. Nucleocapsid to host cell nucleus, ***viral polymerases require methylated cap*** of RNA _^{(Cap-mRNA-Poly A)}_ of host cell. Cap region of RNA for binding to ribosomes. 4. (+) RNA made from each segment=***viral polymerase*** on each segment(-)sense RNA for viral progeny made=**^{viral Shedding}** 5. ***+mRNA proteins*** in cytoplasm. 6. ***Early proteins (polymerases and NP)*** for transcription and replication go to nucleus and ***mix w/–ssRNA.*** 7. ***HA and NA , M proteins*** transported to host cell membrane.

Question 33

RNA virus (enveloped) Influenza-Types

Answer 33

* **_Type A_** ONLY one w/sub-types based on variation on HA/NA Ag * 16 HA sub = ***H1-H16*** * 9 NA sub = ***N1-N9*** * Found in many species_-Native host is duck_ * Type A assoc w/Pandemic ^{(Spanish Flu)} * **_Reassortment Antigenic shift:_** * Abrupt change when 2 strains infect one cell=RNAs mix giving rise to NEW strain * ***ONLY A*** * **_Type B_** ***ONLY humans*** * Point mutation/Antigenic shift: * Type A&B-Yearly epidemics occur * ***RNA segments are altered*** affect major Ag sites for glycoproteins * RNA virus prone to ***more mutations*** than DNA * ***Peplomers mutation***=Cross species infect

Question 34

RNA virus (enveloped) Influenza-Clinical

Answer 34

* Incubation 1-4 days * Fever, headache, sore throat, muscle pain, ***DRY cough*** * Recovery 7-10 days * Severity in ***young & elderly*** ALSO pts w/chronic cardio-pulm diseases * Pneumonia caused by Influenza * Pneumonia caused by secondary bacterial infection-MOST COMMON ***(Staph aureus, Staph pneumoniae, H. Influenzae)*** * **_Reye's syndrome-_**Acute encephalomyelitis**_^{(inflammation of CNS)}_**in children-assoc w/aspirin use * ***CNS issues-***Seizures, weakness in periphery, hallucinations

Question 35

RNA virus (enveloped) Influenza-Diagnosis

Answer 35

* Nasal/throat swabs, sputum * **_Detection=_**Ag/genome DFA, ELIZA, RT-PCR ***specific ID*** for types or subtypes * **_Fast results-_**used in screening during epidemics * **_Viral isolation & ID-Cell/egg culture:_** * Hemagglutination or Hemabsroption assay ***NOT specific*** * **_Serology:_** measure ***Ab lvl (titer)-***Acute hemagglutination inhibition assay, Comp fixation * **_Treatment:_** neuraminidase inhibitors stop viral release given 48 hrs of onset * ***Oseltamivir(tamiflu)-***oral * Zanamivir(Relenza)-inhaled * Stop uncoating-block martix proteins_^{ONLY A}_ * ***Amantadine or Rimantadine***

Question 36

RNA virus (enveloped) Influenza-Vaccine

Answer 36

* **_Flu shot-_**Inactivated vaccine (killed virus) * Composed of H1N1, H3N2 + type B * **_Nasal spray vaccine_**: * Live attenuated=Reconstructed from mutant strain & virulent strain (weak)=***Reassortment*** * Mutant strains does NOT grow well above 25C=***Cold adapted mutant*** * ***Will grow in upper*** BUT not Lower resp making it less virulent