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54 Cards in this Set

  • Front
  • Back
Whats rhinitis?
– inflammation of internal area of nose caused by Rhinoviruses and coronaviruses
Rhinoviruses differs from other enteroviruses in that
Replication limited to the respiratory tract
Due to acid liability (pH=6 inactivates)
Optimal replication at 33 C
Rhinovirus pathogenesis
1) Only human reservoir
2)Binds ICAM 1 on upper resp tract epithelial cells
3) extends locally w/o killing cells
4) Local inflammation causes exudate
5) Further ICAM 1 proliferation leads to more viral binding and infection
6) exudate may block passageways
7) Secondary sinusitis or otitis media
Why do we get repeated colds?
-Viral receptor is in a depression (canyon) around the vertices of each pentamer.
-Antigenic determinants of each serotype are located primarily along the canyon rim on the surface of the virus particle.
-Less critical surface residues around the canyon “drift”, giving rise to over 100 serotypes of rhinovirus
Whats the most commonly known effect of rhinovirus?
common cold 50% due to rhinovirus
Coronavirus 30%
Rhinovirus transmission
-Direct contact with contaminated hands & surfaces (fomites)
Most efficient
-Inhalation of infectious droplets
Who is at risk of rhinovirus?
Everyone

Rate of clinical symptoms decrease with age
Attributed to partial immunity from past exposures
Rhinovirus most commonly in
Early fall-late spring
Influenza more common in
Winter-Jan-Mar
Patient presents with runny nose, sneezing and irritable throat and a slight fever. She suffers similar symptoms every year often at the same time as other members of her family. Her symptoms go away within a week, except for the nasal discharge that persists for a few months
Rhinovirus
Rhinovirus diagnosis
Typically made based on clinical criteria
Symptoms of several common cold viruses are indistinguishable
Usually do not test to identify specific “common cold” virus
Complaining of feeling tired and achy for few days
Today: Congested, thick yellow nasal discharge
Non-productive cough started this morning
No fever
the common cold
whats the relation between common cold and Acute Bacterial Sinusitis
Acute bacterial sinusitis is a complication of colds. And it is a small percentage of the cases.

Nasal congestion/ purulent nasal discharge WITH facial pain
Persistent; no improvement >10-14 days or worsening after 5 day
Common cold tx
hydration and rest
Coronaviridea Characterization
Positive sense ss RNA genome (27-30kb)
LARGE (27-30kb) (largest RNA virus)
RNA is capped and polyadenylated like mRNA

Enveloped
Irregular shaped particles (100-160nM)
Except for SARS coronaviruses infection limited to
limited upper respiratory tract
Due to Optimal replication at 330
Severe acute respiratory syndrome
coronavirus
SARS-CoV)
Coronavirus Features
Envelope glycoproteins
S - Spike (formerly E2)
Receptor binding
Cell fusion

E - Envelope (formerly sM)
Small, envelope protein
(not as abundant as S)

M - Membrane protein (formerly E1)
Transmembrane
Budding & envelope formation
Coronavirus Replication
ENTRY:
Spike (E2) glycoprotein binds cell
virus fuses & releases RNA into cytoplasm

PROTEIN SYNTHESIS PHASE I:
Translation of RNA-dependent Polymerase

REPLICATION:
Negative Strand Synthesis
(RdRp uses viral genome as template
for minus strand RNA synthesis)

Positive Strand Synthesis
(RdRp uses negative strand as template
for genomic RNA AND a nest set of 3’
co-terminal mRNAs)

PROTEIN SYNTHESIS PHASE II:
All other viral proteins are translated

ASSEMBLY AND SECRETION:
Genome associates with Nucleocapsid proteins, which buds into ER for exocytosis
Coronaviruses infection can be asymptomatic but can cause enteric infections in
infants younger than 1 yr
Cornavirus Transmission:
Direct contact with contaminated hands and surfaces
Inhalation of infectious droplets
Who is at risk for coronavirus infections?
Everyone, but rate higher in children
(Re-infection can occur even in presence of serum antibodies)
When is coronarivures most common
Dec-May
SARS Unique Pathogenesis
Causes upper and serious LOWER respiratory illness
Asymptomatic or mild illness uncommon
SARS Transmission:
Patient-to-patient variability in transmission efficiency
Seems to correlate with illness & viral titers
(Reservoir believed to be wild horseshoe bats)
Who is at risk of getting sara?
Everyone, BUT
Age is important risk factor for severe disease
Children have less severe illness than adults
Fatality in the elderly can approach 50%
Why might age-based response be different than common cold
were children have worse illness?
Age based response is different because the damage is due to immune system mediation. Older people have co-morbidities that worsen the condition.
Coronavirus replicates best at
33 - 35 0C and is therefore usually restricted to upper respiratory tract
Whats the clinical SARS manifestation?
Phase I – Systemic illness (fever, myalgia, chills, headache)
Phase II – Respiratory illness (cough, SOB, O2 desaturation) & diarrhea


3) Recovery or progressive respiratory failure
SARS Case Suspicion
High fever (>380C) with
Cough or breathing difficulty and:

-close contact with a probable case of SARS
-history of travel to an affected area
-residing in an affected area

SARS Case Probable

The above with evidence of change on chest X-ray
SARS reservoir is
wood bat
The single most important cause of
severe diarrheal illness in infants and
young children in both developing and
developed countries worldwide
Reovirus
Whats the only virus that is dsRNA and affects humans?
Reoviridae Rotavirus
Reoviridae Rotavirus structure
Non-enveloped, icosahedral particle
- tough two-layered structure
- can survive in the environment
Reoviridae Rotavirus tropism is for
Differentiated Enterocyte
(small intestine)
How does Rotavirus infect?
an intermediate/infectious subviral particle (ISVP)

The ISVP binds, penetrates the cell, and loses its outer capsid

Inner capsid enters host cytoplasm (which contains the viral polymerase
Whats the ISVP?
It is the rotavirus with the minor outer membrane capsid (major (VP7) is digested by GI tract proteases)
Attachment Protein VP4 is exposed
Whats the core of the rotavirus composed of?
Inner capsid contains the enzymes for RNA synthesis
-
Rotavirus replication
viral mRNAs synthesized from negative-strand of genome
-viral mRNAs released into cytoplasm

Host cell ribosomes translate viral proteins
Viral proteins and positive-sense RNA associate into core structures

Viral negative strand RNA synthesized in the core (to re-create dsRNA genome

Core Structures aggregate into large cytoplasmic inclusions

Virus Assembly and Release:
Orthoreovirus
transmission
- respiratory & fecal-oral
Ortheovirus affects
individuals are infected in childhood
-75% to 80% of adults have antibodies
Ortheovirus detected by
by RNA
-throat, nasopharyngeal, and stool specimens
-No specific diagnostic tests recommended
No specific treatment recommended
One of the most common tick-borne diseases in US
Virus infects erythroid precursor cells resulting viremia that may last for weeks & aids in transmission of virus to tick
Coltivirus and Orbivirus
Coltivirus most common in
March to September (Spring to Fall)
Coltivirus colorado tick fever manifestation
Biphasic disease :
Fever, chills, headaches, pain behind the eyes, light sensitivity, severe myalgia & lethargy, abdominal pain, nausea, rash
Rare Outcomes include:
Neuronal infection causing aseptic meningitis, encephalitis
Hemorrhagic disease from infection of vascular endothelial

Diagnosis: - Patient’s recent activities/location or presence of TICK

Treatment: – No specific treatment other than remove tick
the primary cause of infantile diarrheal disease
rotavirus Group A: G1 (VP7 serotype) accounts for 73% of infections
Who is at Risk? of rotavirus type A
Infants at risk for infantile gastroenteritis
Older children and adults at risk for mild diarrhea
Who is at Risk?
Rotavirus Type B
Everyone at risk for severe gastroenteritis
Mainly found thus far in China
Rotavirus most common in
common in fall and winter
Rotavirus Clinical Manifestations
Disease:
Asymptomatic or Severe
First infection generally being the most severe
Symptoms
Dehydrating diarrhea with fever and vomiting
Electrolyte imbalance
Generally resolves in 3 to 7 days
Rotavirus Disease Mechanisms
Typical viral pathology
Cytolytic release of virus

First viral enterotoxin
Toxin-like action of viral protein NSP4 on the intestinal epithelium
Increases intracellular Ca++
Effects PM permeability
Resulting in loss of electrolytes & impairs water absorption.

MECHANISM SIMILAR TO BACTERIA
Rotavirus Treatment
Supportive Therapy:


Replace fluids so that blood volume, electrolyte and acid-base imbalances are corrected

Oral Rehydration Salts (ORS) Solutions
Intravenous fluid administration
Rotavirus Prevention
problem
Natural infection does not provide complete
protection against subsequent infection

Very unlikely we can develop a vaccine more
effective than the virus itself


Result: The aim of any Rotavirus vaccine is not necessarily to prevent infection, but prevent
severe gastroenteritis
Rotavirus Two Vaccines
Rotavirus Vaccine (RotaTeq®)

Approved by FDA in February 2006
5 re-assortant rotaviruses from human & bovine strains
Received ACIP* recommendation for routine vaccination

Rotarix® Rotavirus Vaccine
Approved by FDA in April 2008
1 strain of live attenuated human rotavirus (G1P1A)