Lecture 3 Enveloped Viruses Flashcards
Which classes are viruses have we learned about that are enveloped?
orthomyxo-, paramyxo-, herpes-, toga-, flavi-, rhabdo-, hepadna-, retro-, and pox-
What are the two surface prots on the envelope of Influenza, and what do they do?
Hemagluttinin - Binds sialic acid on host cell surface; named for its hematogluttinating activity; serves as the major Ag for Ab production; Abs bind here and block the ability of the virus to adsorb to host cells
Neuraminidase - degrades sialic acid which, while beneficial in helping the virus particle adsorb to host cells, acts a “velcro” as the progeny virions try to bud out
What are the three types of INF and which is secreted by what?
alpha and beta from virus-infected cells
gamma - from antigen-stimulated T-cells
How does cell know when to release INF?
pattern recognition receptors (e.g. TLRs) recognized viral RNA
What are virus inhibitory proteins, and how do they work?
Virus inhibitory prots like 2-5-A synthase and prot. kinase R (PKR)
Synthesized by uninfected cells when INF binds their cell-surface INF receptors
Require 1) INF activation of cell, AND 2) infection w/ dsRNA
–Work to block protein synthesis
2-5-A Synthase mech
synth 2-5-A which activates a ribonuclease that destroys mRNA, halting prot synthg
(name = adenosines linked by a 2’ to 5’ phosphodiester)
How does protein kinase R work?
Protein Kinase R (PKR)
P’s eIF2, inactivating it
Influenza
Family = ?; Genus = ?
Epidem/trans —>what strains, how are they different? how do they mutate?
Pathogen w/ s/sx = ?
Dx = ?
Vaccines? = ?
Tx = ?
Family = orthomyxoviridae; Genus = e.g. Influezavirus A
EPIDEMIOLOGY AND STRAINS
3 strains:
A = worst
B = less severe, epidemics q3-6 yrs
C = NBD
MINOR EPIDEMICS (i.e. yearly) due to antigenic DRIFT (i.e. mutation w/in existing RNA segments, specifically H gene); we’ll have partial immunity to this from previous immunization/illnesses
MAJOR PANDEMICS due to antigenic SHIFT involving reassortment of animal and human influenza strains; must be an H-shift, even worse if there is concomitant N-shift; this will be a Novel H (and N) which means we will have NO immunity
TRANSMISISON: droplets and surface contamination
Pathogen w/ s/sx = even though locatlized infection in resp tract (i.e. usually no virema)—>systemic sx incl. f/c and myalgia from pro-inflammatory mediators; destroys cilia of resp tract
—can develop 2° viral pneumonia—>leads to bacterial pneumonia
Dx = rapid uses fluorescent Ab on throat swab specimen; compare acute and convalescent Ig levels
Vaccines = usually killed virus trivalent w/ 2 A strains and 1 B strain given IM
FluMist = polyvalent, live, attenuated —>induces IgA
new quadrivalent just out w/ 2 A and 2 B strains
Tx = neuraminidase inhibitors (e.g. osteltavir, zanamivir) for both A and B; amantadine and rimantidine—>only A and then only sub-set of As
RSV
Family = ?; Genus = ?
Epidem/trans —>Pathogen w/ s/sx = ?
Dx = ?
Vaccines? = ?
Tx = ?
Family = Paramyxoviridae
Epidem/trans = trans like flu (direct droplets and indirect surfaces); outbreaks in winter; occurs worldwide and virtually everyone has been exposed by 3 y/o
Pathogen w/ s/sx = LOWER resp tract—>bronchiolitis and pneumonia more severe in infants—>hospitalization; can have immunopathogenic mech w/ maternal IgG forming immune complexes and injuring baby’s lungs
Dx = rapid antigen testing of resp secretions; CPE w/ giant, mulitnuc cells; RT-PCR; 4x rise in Abs
Vaccines? = no vaccine
Tx = inhaled ribavirin (unsure how well it works); maybe combine with hyperimmune Igs
Croup
Family = ?; Genus = ?
Epidem/trans = ?
Pathogen w/ s/sx = ?
Tx = ?
Family = Paramyxoviridae; (Genus = Respirovirus & Rubalavirus;) Species = Parainfluenza (most common cause; other viruses can cause similar syndrome)
Epi/trans—> first three years of life
Pathogenesis = “acute laryngo-tracheo-bronchitis” causing dyspnea and stridor
Tx = glucocorts w/ bad cases
SARS
Family = ?
Epidem / Trans = ?
Pathogen w/ s/sx = ?
Dx = ?
Vaccines? = ?
Tx = ?
Family = Coronaviridae
Epidem/trans = human-to-human trans
Pathogen w/ s/sx = 1-3 days incubation; severe infection uncharacteristic of other coronaviruses; pneumonia w/ diffuse edema—>hypoxia; binds to ACE-2 which may play role in edema
Dx = PCR- and Ab-based tests used to dx SARS
No vaccine nor specific antiviral; ribavirin + steriods
Orthomyxoviruses
Nucleic acid set-up?
Virion structure?
How does it multiply?
Examples?
NA = multiple (-)ssRNAs (each in their own helical nucleocapsid)
virion = enveloped helical
REPLICATION:
1) Virion dsorbs to cell via H->sialic acid interaction
2) virion contains RNA-dep RNA pol b/c genome is (-)ssRNA, but unique to RNA virus, it replicates its genome in the NUCLEUS
3) Translation and assembly in the cytosol
4) Bud out
EXAMPLES: influenza
Paramyxoviruses
Nucleic acid set-up?
Virion structure?
How does it multiply?
Examples?
NA = single (-)ssRNA
Virion = helical enveloped
REPLICAITON:
1) also uses hemagglutinin to adsorb to cell
2) have only one RNA segment (therefore no antigenic shift) and replicates genome in cytosol, but otherwise similar to influenza/orthomyxoviridae: Virion contains RNA-dependent RNA pol, budding, etc.
EXAMPLES: parainfluenza (Croup), RSV, Measles, mumps
