L6 Flashcards
Influenza type
Orthomyxoviridae
Influenza genome
Segmented (-)ssRNA
Influenza virion
Enveloped
Adenovirus type
Adenoviridae
Adenovirus genome
dsDNA
Adenovirus virion
Non-enveloped
Rhinovirus type
Picornavirus*
Rhinovirus genome
(+)ssRNA
Rhinovirus virion
Non-enveloped
Three types of influenza virus:
A, B, and C
Type A most common and associated
Influenza
with greatest concerns
Influenza Identified by
surface antigens HA and NA
16 HA serotypes
9 NA serotypes
Influenza Avian vs. Human Strains
HA major determinant (a.a. 138 & 227 key role)
a2,3 sialic acid linkage = Avian
a2,6 sialic acid linkage = Human
NA specificity (like HA) & PB2 (point mutation) HA major determinant for human to human transmission
Type A has
Influenza
animal reservoir
Influenza HA protein’s role in cell
attachment and entry is well understood
Influenza Attachment brings cell and virus
membranes into proximity (A)
Conformation change triggered after
cell attachment by pH change in endosome
Causes membrane fusion (B)
Model for all enveloped viruses
Influenza Transcription and replication take place in
nucleus
Protected genome (RNP core) escapes
nucleus and buds from cell surface
NA critical to
budding
Influenza Transmission by
aerosol, large and small droplets
Infectivity greatest for particles <10 microns
ID50 as low as 0.3 to 6, 50% egg infectious doses (EID50)
Influenza Incubation time
1-4 days
Contagious day beforesymptom onset to 5 days later, children are infectious for longer
Influenza Seasonal (interpandemic) flu
Fever, malaise, nonproductive cough, sore throat
Lasts 3 to 7 days after symptoms develop
Influenza Currently circulating strains:
H3N2, H1N1
Influenza Contagiousness
Reproductive number:
1 to 2
Influenza complications
Viral pneumonia
Bacterial pneumonia
Reye syndrome (Type B + aspirin)
Otitis media
Influenza Attenuated live vaccine
Virus mutations require newvaccine development every year – antigenic shift
Long lead time
Usually contains an H3N2, H1N1, and Type B strain
Type A strain generated through reassortment via coinfection with PR8 strain
Influenza Antiviral treatment
Amantidine, rimantidine
Blocks entry, inhibits M2 activity
Development of resistance common
Influenza Zanamivir or oseltamivir (Tamiflu)
Blocks release of budding virions
Development of resistance is not common
1918 Spanish Flu
H1N1 strain
20-40 million deaths
Virulent in healthy adults; cause “cytokine storm” in lethal cases
1957 Asian Flu
H2N2 strain
6 million deaths, mostly elderly and young children
1968 Hong Kong Flu
H3N2
2 million deaths
2009-2010 H1N1
8,000 to 18,000 deaths
Influenza Pandemics are thought to arise from
avian strains
Highly Pathogenic Avian Influenza
H5 or H7 strains
Lethal in >75% of 6-8 week old susceptible chicks
HPAI strains have multi-basic residues at HA cleavage site allowing replication throughout the body
Skin lesions, necrotic & swollen combs, systemic infection
Low Pathogenic Avian Influenza
Asymptomatic to slight respiratory infection, no lesions
H5 and H7 strains can mutate to
HPAI strains
Dutch research caused great
controversy
Used H5N1 strain, high mortality rate in people
Could H5N1 adapt to
humans?
Passaged virus in ferrets
Model for human infection
After 10 generations virus was capable of airborne transmission between animals
Five mutations in two genes
UW-Madison research identified mutations in HA that alter sialic acid binding
Mortality still high for infected animals
Adenoviruses characterized by their
serotype
Different serotypes associated with different diseases – Ad 2 & 5 most frequently studied
Entry via
Adenovirus
coxsackie-adenovirus receptor (CAR)
Adenovirus have pH triggered
capsid disassembly
then Moves to nucleus
Adenovirus Gene expression in three phases
Immediate-early: E1A portion of genome 2 transcriptional regulators (cell & virus) Necessary to reach early stage Early: 5 genome sections E1B, E2, E3, E4, and L1 DNA replication & post transcriptional events Late Take over of cellular mRNA synthesis
Genome replication
Adenovirus
Initiated on either end, identical end sequences
Replication in 5’ to 3’ direction, one strand displaced
Displaced strand circularizes to allow template copy to be made
Primed by the protein pTP, unusual priming strategy
Adenovirus Cell Cycle Regulation
DNA replication occurs during S phase
Not all cells are actively replicating
E1A inactivates pRb leading to S phase gene expression
E1B inactivates p53 leading to S phase and preventing apoptosis
Similar to oncogenic processes
Adenovirus E3 gene produces
proteins important to host immune evasion
Adenovirus Blocks
MHC class I expression reducing CTL cell killing
Blocks TNF
induced apoptosis
Adenovirus Blocks IFN-α & IFN-β action keeping
protein translation active
Respiratory infections very common
5 to 10% of all viral infections
75% occur before the age of 14
Adenovirus Typical symptoms same as the common cold
Nasal congestion, inflammation, cough
Serotypes 1, 2, 5, & 6
Acute respiratory disease (ARD)
adenovirus
Severe pneumonia - seen in military recruits, crowded conditions & fatigue are risk factors
Serotypes 4 & 7
Vaccine available for military personnel 17-50 yrs old
Rhinovirus Frequent cause of
mild upper respiratory infections
Rhinovirus Large antigenic diversity
Over 100 serotypes
Makes vaccine development impractical
Rhinovirus Humans only known
reservoir
Rhinovirus Attaches to intercellular
adhesion molecule 1 (ICAM-1) or the very low density lipoprotein (VLDL) receptor
Rhinovirus Incubation period
1 to 4days
Rhinovirus Duration
2 to 3 days withdetectable virus shedding
Virus shedding sometimesdetected up to 3 weeks afterwards
Rhinovirus Symptoms
Red nose (hyperemic), blood vessel dilation Nasal discharge that becomes mucopurulent (neutrophils) Epithelial damage likely due to the immune response
Rhinovirus Prevention
No vaccines: too many serotypes
No antivirals: resistant mutants
Ebola Virus
Filovirus
Polymorphic particle, enveloped
-RNA genome
Helical nucleocapsid
Ebola transmission
Transmission
Primarily body fluids
Some evidence for inhalation
Ebola disease
Viral hemorrhagic fever
Fever, headache, vomiting,diarrhea, bleeding
Incubation 2-21 days
Ebola treatment
Supportive care
Experimental treatments
Vaccine – ChAd3-ZEBOV,VSV-EBOV, others