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Picornavirus:
Family?
6 Genus?
- Family: Picornaviridae
- Genus:
- Rhinovirus- common cold viruses (HRV)
- Enterovirus- poliovirus, human Enterovirus A, Coxsackie A and B, ECHOvirus
- Apthovirus- foot and mouth disease virus (cows)
- Cardiovirus- EMCV and Mengo (mice)
- Hepatovirus- HAV
- Paraechovirus- diarrhea/respiratory infxns in children
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Picornaviridae Structure:
Genome?
# of ORFs?
Enveloped?
Nucleocapsid shape?
# of proteins that make up virion?
- ssRNA
- 1 ORF
- Naked
- Icosahedral nucleocapsid
- 4 proteins make up virion
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Receptor locatio of picrnaviridae
Deep in cleft (on Bp1 or Bp3), Ig's can't fit into the cleft.
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What structure is made when picornavirus replicates?
dsRNA structures
*Protease cleans up the final structure
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First replicative event of Picornavirus replication
Genome is translated to yield structural and catalytic proteins
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Viral proteins are synthesized to form
A large polyprotein
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Polyprotein is then co-translationally cleave dby
virus-encoded proteases to generate the final products
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Final products of Picorna virus replication
- 4 capsid proteins
- 2 proteases
- VPg
- RDRP
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Directs synthesis of negative-strands via a ds replicative form
RDRP
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Negative strands then serve as templates for positive strands via the multi-stranded
Replicative intermediate
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2A protease encoded by
CxB4
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2A protease cleaves (3 things)
- viral polyprotein (via a self-processing mechanism)
- eIF-4G -> host translational shut-off
- Heart muscle dystrophin -> cytoskeletal dysfunction
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Causes infection of heart muscle myocytes
Coxsackie B4 virus
Significant cause of human acquired dilated cardiomyopathy
Disease is characterized by cardiac enlargement and CHF
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Coxsackie B4 virus cleaves
Dystrophin -> leads to disruption of hte extrasarcomeric cytoskeleton and loss of transmission of mechanicla force to the ECM
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Man is the only host for
human enteroviruses
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Transmission of Enteroviruses
Fecal-oral, droplet
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Clinical presentation of Enteroviruses
Clinical presentation is NOT definitive; lab tests are needed
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Tx for Enteroviruses:
- Supportive
- Vaccination for polio
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Peak incidence of Enteroviruses
Summer/fall
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Enterovirus Immunity
- Local IgA blocks infxn
- Systemic IgG blocks paralysis due to poliovirus
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Infect and affect a wide range of organs and tissues
- Enteroviruses
- Picornaviruses
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Enteroviruses cause
- Aseptic meningitis (encephalitis)
- URTIs
- Paralytic disease
- Fatal generalized disease in newborns
- Epidemic hemorrhagic conjunctivitis
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Exposed to poliovirus by
ingesting it
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Polio virus grows in
Oropharyngeal mucosa or gut --> then it goes to lymphoid tissue
Once it gets into the blood, it can target more important tissues such as CNS (polio) etc.
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Problems with live poliovaccine
Live vaccine can cause paralytic disease in an immunocompromised person.
Or it can mutate and cause virus.
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Poliovirus percentages:
Asymptomatic?
Malaise?
Paralysis?
- Asymptomatic= 95%
- Malaise= 1-5%
- Paralysis= <1%
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Target of polio that results in paralysis (flaccid paralysis, pain; bulbar paralysis)
Anterior horn cells
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Polio is a disease of
developed countries (undeveloped countries get it when they're younger and still have maternal Ab protection)
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Polio Prevention
- Salk Vaccine: IPV
- Sabin Vaccine: OPV
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Salk vs. Sabin: Dropped on sugar cubes or just dropped in your mouth
Sabin
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Only 3 countries with endemic polio
- Afghanistan
- Pakistan
- Nigeria
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Salk vs. Sabin: No virus-specific CTL response. No mucosal Ig!
Salk
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Salk vs. Sabin: Tc response and IgA, protected population; Virus specific CTL response is generated w/ mucosal Ig
Sabin
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Characterized by muscle pain, and progressive muscle weakness
Post-Polio Syndrome
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Enterovirus Disease: Epidemic myalgia, intercostal pain (Devil's stitch)- unilateral thoracic chest pain
Endemic in Danish Island
Pleurodynia
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Enterovirus Disease: A childhood infxn characterized by fever, sore throat, and vesicular lesions within throat
Herpangina
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Herpangina is caused by what forms of Enteorvirus
EnA, EnC (Coxsackievirus A)
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Enterovirus Disease: A childhood infxn characterized by lesions in the mouth and on the palms and soles
Common in pre-schoolers
Hand-foot-mouth disease
Coxsackievirus A6 variant is linked w/ nail loss months after initial infxn
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Enterovirus Disease: Painful eye infxns that are easily spread from person-to-person
Acute hemorrhagic conjunctivitis
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AHC cause by
En70, CxA= EnC, EnD
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Enterovirus Disease: A multi-system illness developing soon after birth and linked to a high fatality rate
Neonatal disease
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Neonatal disease caused by
CxB and ECHO (EnB)
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Enterovirus: EnB myo- and peri-carditis in adults and children
Cardiac Disease
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3 Differential Diagnoses for mouth lesions
- Hand-foot-mouth syndrome (enterovirus, CxA)
- Herpangina (enterovirua, CxA)
- Primary Herpes Gingivostomatitis (HSV-1, sometimes HSV-2)
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Diagnosis of aseptic meningitis is made by
Excluding bacterial causes
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Meningitis:
500-10,000 cell/ul (mostly PMNs)
Bacterial
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Meningitis
10-500 cells/ul (mostly lymphocytes)
Viral meningitis
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Virus decontamination: Bleach or alcohol?
bleach
alcohol only targets the capsid
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Rhinovirus transmission
direct contact
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HRV is responsible for what percentage of:
common colds?
asthma exacerbations?
- 30% of common colds
- 50% of asthma exacerbations
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Rhinovirus Immunity
Type-specific, involves mucosal IgA
Vaccine is problematic due to large # of straings
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Only family of positive-strand viruses w/ a helical nucleocapsid
Coronaviruses
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# of ORF proteins in coronavirus
9
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16 of Coronaviruses 28 proteins are generated by
Polyprotein
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Cleavage of ORF1a/1b polyprotein is mediated by
virus-encoded proteases -> gives rise to proteins required for RNA replication
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CoV ORFs 2-9 encode
Structural proteins
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SARs is what type of virus
Coronavirus
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Origin of SARs
Bat-> Civet Cat -> People
(Classic example of a zoonotic infxn in which bats play a key role)
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Coronavirus that causes serious URTI in elderly
SARS
*Can be controlled by preventative measures
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SARS incubation period?
SARs duration of illness?
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Increased virus shedding due to advanced disease or co-morbidities
Super Shedder
One of the driving forces behind the early SARS outbreak (vast majority of pts. don't transmit the virus effectively)
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Increased contact with respiratory secretions, contact with highly contagious pts., exposure to aerosol-generaing procedures
Nosocomial Amplification (NA)
One of the driving forces behind the early SARS outbreak (along with SS)
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SARS mortality
10-15% overall, but increases with age
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SARS-CoV receptor
Angiotensin-converting enzyme 2
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ACE2 is the receptor for
SARS (CoV)
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SARS MoA
Virus replication leads to hyperimmune activation which triggers pulmonary destruction
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Viruses that cause GI Tract Illnesses
- Rotavirus (Family Reoviridae)
- Norovirus (Family Caliciviridae)
- Astrovirus
- Enteric adenovirus
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Family that rotavirus belongs to?
Other genera within that family
Reoviridae
- Reovirus: minor human pathogens
- Orbivirus
- Coltivirus: Colorado Tick Fever Virus
- Rotavirus: causative agent of severe diarrhea and vomiting (7 serogroups within genus)
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Structure of Rotavirus
- dsDNA (11 segments)
- Non-enveloped icosahedral virus
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Rotavirus is responsible for 5-10% of all diarrhea episodes in children <5 years old.
Within the first 5 years of life 80% of American kids will be infected with rotavirus...immunity is lifelong
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Rotavirus:
Incubation period
Illness lasts
- Incubation period: 1-4 days
- Illness lasts: 5-8 days
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Rotavirus is most prevalent in US
during cooler months
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Rotavirus transmission
Fecal-oral route
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Classification of Rotaviruses is based on
Viral capsid proteins VP4 and VP7
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VP4 and VP7 are viral capsid proteins for what virus?
Rotavirus
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How many Rotavirus human serotypes are based on VP7
10 (G1-G4, and G9 are the most common)
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Main targets of neutralizing Ab for rotavirus
VP4 and VP7
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2 Rotavirus vaccines
RotaTeq- pentavalent, live attenuated, expresses various subtypes of human VP7 outer capsid protein (G1, G2, G3, and G4) and the human VP4 attachment protein
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Following the introduction of RotaTeq/RotaRix, the # of rotatvirus infxns was reduced by
> 50%
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Causes 60% of foodborne illness
Norovirus
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Common in day cares, cruise ships, and elderly ppl homes
Norovirus (foodborne illness)
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Norovirus family
Caliciviridae
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Norovirus genome
Single molecule of + sense RNA
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Norovirus is divided into how man ORFs?
3
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Norovirus ORF1
Encodes a large polyprotein which undergoes proteolytic cleavage to produce viral proteins that are homologous to proteins from other ssRNA viruses
Also encodes RNA-dependent RNA Polymerase
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NoV genogroup
- 5 different genogroups
- Based on the genome sequence of the RdRp and the capsid regions
Only genogroups 1, 2, and 4 have been associated with human gastroenteritis
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Norovirus genotyping has been complicated by
Recombinant norovirus strains
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Norovirus: Viral shedding
May persist for 7-14 days
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Norovirus Diagnosis
- ELISA- detection of anti-viral Abs
- RT-PCR
- Nucleic acid hybridization probes
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Rotavirus vs. Norovirus
- Rotavirus: Severe diarrhea, vaccine available
- Norovirus: Brief GItis, no vaccine
Diarrhea is the result of both direct and indirect effects of virus
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Viral GIitis
Shortening of the intestinal villi leads to malabsorption of fats and sugars resulting in profuse watery diarrhea
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Enteric Adenoviruses
Ad40, Ad41 may account for 4-15% of children hospitalized with VGI.
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Enteric Adenoviruses:
Incubation period
Duration of illness
Symptoms vs. rotavirus
- IP= 8-10 days (longer than Rotavirus)
- DoI= 6-12 days (longer than Rotavirus)
Symptoms less severe than with rotavirus
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Similar to caliciviruses in shape and genome organization. Major cause of childhood diarrhea worldwide. 1-4 day incubation, ~4 days of illness, less severe than rotavirus
Astroviruses
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Viral Vaccines: 0-6 years
HBV (3), Rotavirus (2-3), Poliovirus (4-5), Influenza virus (yearly), MMR (2), Varicella (2), HAV (2)
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Viral Vaccines: 7-18 years
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Viral Vaccines 19->65 years
Zoster (1), Influenza (yearly)
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Viral Vaccines: Others
Rabies, Japan B Encephalitis, Yellow Fever Virus, Vaccinia (smallpox)
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