Enveloped/flu Flashcards
Production of enveloped virus
viral RNA -> protein -> Golgi -> cell membrane
virion -> membrane ->
BUDS OFF!
not lysis - cell doesn’t die immediately (vs non-enveloped)
Envelope
Lipids - from host cell membrane
Proteins - from virus genome -> specificity for receptors
Appears clear with “rods” = proteins
Enveloped vs non-enveloped
Antigens - envelope protein vs capsid protein
Envelope -
- sensitive to ether, organic solvents (-> lipids)
- unstable outside of host (dessication vs fecal oral capside crystal)
Release via budding (not fatal) vs lysis of cell
Structure of flu virus
Enveloped orthomyxo
- proteins = hemagglutinin (antigen, binds to host sialic acid)
= neuraminidase (target for antiviral)
RNA - 8 strands, (-) strand (not mRNA)
- each strand in separate helical nucleocapsid
RNA-dependent RNA polymerase
Classes of enveloped viruses
Paramyxo Toga Herpes Flavi Orthomyxo (flu) Rhabdo Retro Pox Hepadna
Hemagglutination assay
Orthomyxoviruses contain hemagglutinin protein (HA)
- HA binds sialic acid on RBC’s -> complex vs “button”
- inhibited by antibody (neutralizes HA -> button)
Can assess:
- viral concentration (dilution that still forms complex)
- antibody concentration (dilution that prevents complex)
Flu antigens
Capsids - around RNA segments but hidden!
Hemagglutinin (HA) - necessary for adsorption (binds to sialic acid)
- can be neutralized by Ab
Neuramidinase (N) - necessary for release of new virions
(cleaves sialic acid-HA bonds)
- Ab slows spread (to other cells, people) but does not neutralize virions or prevent infection of new cells
Types of flu
3 types (A,B,C) - defined by capsid protein (A,B,C) Antigenic differences within type - HA, NA, polymerases, etc
A - most serious, epidemic q2-3 years, pandemic q10-30 years
B - less serious, epidemic q3-6 years
C - not significant
Vaccine = 2 A + B
Minor epidemics
Antigenic drift = minor mutation in existing RNA
- usually mistake in HA gene -> conformational change
- some existing antibodies bind (partial immunity)
Major pandemic
Antigenic shift of HA antigen (genetic reassortment)
- existing antibodies can’t neutralize -> no preexisting immunity
Sometimes N antigen also shifts
-> more severe bc N antibody can’t slow down spread
Diagnosis of flu
Rapid - fluorescent antibodies -> throat swab
Normal - seroconversion (increase in anti-HA antibodies)
Definitive - culture in eggs or tissue -> isolate
Flu clinical presentation
Aerosol spread (cough, sneeze) -> URI (can cause -> lower respiratory)
Destroys ciliated cells (can cause -> Pneumococcus pneumonia)
Inflammatory mediators -> fever, chills, H/A
Does NOT spread through viremia
Death - infant, elderly, previous lung compromise
- 1918 young adults died: strong immune response -> lung damage
Immunity to flu
Does not spread by viremia! (infects local resp tissues only)
- > short incubation period (days)
- > main protection is secreted IgA
- we are better at neutralizing viremic vs local…
Flu vaccine
Trivalent (2 A strains + 1 B) Strains selected in anticipation of epidemic Killed (formaldehyde) -> IM injection -> only induces IgG response - no IgA produced! sub-optimal
Also have intranasal attenuated (separate slide)
Attenuated flu vaccine
aka FluMist 2 A strains + 2 B strains Attenuated - can't grow at body temperature Intranasal spray -> IgA response! more effective! Approved for ages 2-49
Flu medications
Oseltamivir (Tamiflu)
Zanamivir (Relenza)
Neuraminidase inhibitors - block release of new virions
- shortens symptomatic period
- must be given before or soon after infection
- active against A and B
Adamantanes = older, not recommended
- only work against A, lots of resistance, some side effects
- may be useful in combination, prophylactic
- works by inhibiting polymerase
Flu replication
HA binds to sialic acid -> endocytosis -> fuses ->
releases RNA strands and polymerase ->
translocate to the NUCLEUS! -> makes (+)RNA -> more (-)RNA ->
(+)mRNA (must steal 5’ cap from host transcripts) ->
translation into protein in cytoplasm
Paramyxovirus characteristics
Single (-) RNA
- polymerase in virion
- no reassortment -> less antigenitic variance
Helical nucleocapsid + envelope
Replication in cytoplasm (vs flu in nucleus)
Most non-systemic respiratory
- severe childhood -> no lifelong immunity -> subclinical adult
- all have HA antigen (agglutination test) except RSV
Paramyxoviruses
Systemic: measles, mumps
Non-systemic respiratory:
Parainfluenza (1-4)
Respiratory syncytial virus
Metapneumonia
Croup
aka acute laryngeo-tracheo-bronchitis
Usu caused by parainfluenza
0-3 years (peaks at age 2)
Respiratory - dyspnea and stridor
Treat with glucocorticoids if severe
Respiratory syncytial virus
Most common cause of severe lower resp in infants!
- no vaccine, no long-term immunity (IgA)
Ribavirin - treatment, mechanism unknown
Palivizumab - mAb - prevents pneumonia in high risk (premature)
Does not have HA antigen (hemagglutinin test negative)
Coronaviruses
Enveloped
Helical nucleocapsid
Single +RNA
Common cold
Highly pathogenic = SARS, MERS
SARS
Highly pathogenic coronavirus
2003 epidemic: China -> 8000 people -> 9% fatality
- worst in adults, older
- halted by identification and quarantine
Aerosol -> 2-10 d incubation -> dry cough/SOB -> pneumonia
MERS
Highly pathogenic coronavirus
2012: Jordan, Saudi -> Europe, etc
Severe lower respiratory -> fever, cough, SOB -> 50% fatality
Interferon system
Produced by infected cells (alpha, beta) and activated T (gamma)
-> production of virus inhibitory proteins in non-infected
- induced by pattern recognition receptors (TLR, RIG, MDA) vs viral RNA
- no viral specificity!
- rapidly produced, very transient (vs IgM months, IgG years)
Virus inhibitory proteins
Interferon -> all cells make inhibitory proteins -> activated if infected
2-5-A synthase: makes 2-5-A polynucleotide -> activates ribonuclease L -> degrades mRNA
Protein kinase R: phosphorylates IF-2 -> inactive -> no ribosome
