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Virus

Enterovirus

(Picornaviridae)

RNA VIRUSES
Characteristics
Icosahedral
Non-enveloped
SS+ nonsegmented
Stable at low pH of
stomach

Epidemiology
Spread: contaminated
food/water
Location: stomach
and GIT
Risk Factors:
1. Summer
At Risk:
1. Neonates
(coxsackie,
enterovirus)
2. Children and
adults (poliovirus)

Pathogenesis and Virulence


Pathogenesis
1. Can replicate in various tissues
(tropism)
2. Binds to specific receptors on host cell
surface
3. Viremia: via blood/lymphatics
Virulence
1. Cytolytic
2. Shed in feces for long period
Clearance
1. Antibodies and interferon (secreted
by TH1 cells)

1
Diseases
Poliovirus
1. Asymptomatic Illness (90%)
2. Abortive Poliomyelitis (5%): fever,
headache, malaise, pharyngitis
3. Non-paralytic Poliomyelitis or
Aseptic Meningitis: virus progresses
to CNS and meninges
4. Paralytic Polio: virus spreads to
anterior horn of SC and motor cortex
of brain; spinal paralysis; usually
permanent
5. Postpoliomyelitis syndrome: 20-30%
of patients who recover from PP
experience muscle weakness, atrophy
25-35 years after the illness

Lab Diagnosis
Culture
Serology
PCR
Meningitis: CSF
cytology (inc
lymphocytes,
normal
glucose)

Treatment
Pleconaril
Salk Killed Polio
Vaccine: IgG
Sabin Live
Attenuated
Vaccine: IgG
and IgA

Usually not
required

Self-limiting
No vaccine

PCR: gold
standard
ELISA: viral Ab

Bismuth
salicylate:
reduce
symptoms

Coxsackie A
1. Herpangina: fever, sore throat;
ulceration in mouth and uvula
2. Hand-foot-mouth Disease
Coxsackie B
1. Myocardial and Pericardial Infections:
sudden, unexplained onset of heart
failure; high mortality
2. Pleurodynia (Bornholm Disease,
Devils Grip): unilateral, acute,
excruciating chest pain; vomiting

Rhinovirus
(Picornaviridae)

Norovirus

(Caliciviridae)

Icosahedral
Non-enveloped
SS+ nonsegmented
Acid Labile
Require lower
temperatures
Icosahedral
Non-enveloped
SS+ nonsegmented

Spread: respiratory,
hand to hand
contact
Location: URT

1. Optimal temperature is 33C for


growth (nasal passages)
2. 100 different serotypes: difficult to
establish a protective mechanism

Spread: persons
Location: GIT
Risk Factors:
1. Schools, camps,
prisons, cruises
2. Oysters
At Risk:
1. Adults

1. GIT replication and shed in the stool


2. Inhibits intestinal brush border function
3. Improper absorption of nutrients and
water

Echovirus
1. Viral Meningitis: most common viral
cause; milder than bacterial; CSF:
increased lymphocytes, normal glucose
levels
Common Cold: mild cough,
pharyngitis, malaise, myalgia, low-grade
fever; self-limiting

Adult Gastroenteritis: major viral


cause in adults; nausea, vomiting,
watery diarrhea, self-limiting

RNA VIRUSES

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Rotavirus
(Reoviridae)

Measles Virus
(Paramyxoviridae)

Spread: feco-oral and


respiratory
Location: GIT
Risk Factors:
1. Jan-Mar
At Risk:
1. Infants

1. Initial infection through small intestine


epithelia
2. Toxin-like action: virus causes atrophy
and shortening of villi
3. Decrease reabsorption of sugars and
water diarrhea

Infantile Gastroenteritis: most


common cause in infants; mild to
severe watery, non-bloody diarrhea
with loss of electrolytes

Serology
Electron
microscopy

Ganciclovir
Foscarnet
Screening
reduces
intrauterine
transmission

Helical
SS- non-segmented
One serotype

Spread: respiratory
Location: RT
Risk Factors:
1. Unimmunized

1. Initial infection in RT; attaches to CD46


via Hemaggluitinin (HA); F (fusion) protein
facilitates uptake of virion
2. Replication in respiratory epithelia
3. Viremia: spread to LN, conjunctiva, RT,
urinary tract, blood vessels, CNS
4. CMI controls infection

Measles:
1. Fever, cough, coryza and conjunctivitis
2. Koplik spots: small white spots on
bright red mucous membrane on throat
3. Generalized macular rash: from
head to lower extremities; patient is no
longer infectious

Visual diagnosis
(Koplik spots)

Live, attenuated
vaccine
(MMR)

*No neuraminidase (NA)

Atypical Measles
1. Occur in people with older,
inactivated vaccine
2. More intense rash

Virus recovered
from saliva,
urine
Multi-nucleated
giant cells
ELISA
IF
Hemagglutinin
inhibition
Unnecessary

MMR vaccine

Mumps Virus

Helical
SS- non-segmented
One serotype

Spread: respiratory
Location: RT
Risk Factors:
1. Unimmunized

1. Initially infects RT; local replication


2. Viremia: infects parotid gland

Parainfluenza
Virus

Helical
SS- non-segmented
No viremia
Limited to RT
Common infection

Spread: respiratory,
person-person
Location: RT only
Risk Factors:
1. Nosocomial
At Risk:
1. Infants

1. Only infects the respiratory tract


2. Does not cause viremia
3. Hemagglutinin and neuraminidase
activity
4. Short protective immunity

(Paramyxoviridae)

(Paramyxoviridae)

Icosahedral
Enveloped
Double stranded
Segmented

Complications
1. Otitis media, secondary bacterial
infection, pneumonia
2. Giant cell pneumonia: T-cell deficient
patients
3. Postinfectious encephalitis: rare
(1/1000); autoimmune vs. myelin basic
protein
4. Subacute sclerosing panencephalitis:
rare, slow viral infection with CNS
manifestations
1. Parotiditis: infection and swelling of
salivary glands (primarily parotid);
inflamed ostium of Stensens duct
2. Orchitis/Oophritis: testicular
inflammation; may cause sterility
3. Aseptic Meningitis and Encephalitis:
rare
4. Pancreatitis
1. Croup (serotype 1&2): seal bark
cough; subglottal swelling;
laryngotracheobronchitis
2. Bronchitis and pneumonia (serotype
3): common in infants and elderly
3. Cold-like upper RTI (serotype 4):
treat with nebulized air

Nebulized air

RNA VIRUSES

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Respiratory
Syncytial Virus

Helical
SS- non-segmented

Influenza Virus

Helical
SS- segmented

(Paramyxoviridae)

(Orthomyxoviridae)

Spread: respiratory
Location: URT and
LRT
Risk Factors:
1. Nosocomial
At Risk:
1. Infants
Spread: respiratory
Location: respiratory
tract
Risk Factors:
1. Seasonal: Oct to
May
At Risk:
1. Infants and
elderly
2. Adults: classic flu
3. Seronegative
individuals
4. Immunocomp:
high risk
**Currently, H7N9 is
a pandemic (human
and avian flu strains)

1. HA and F protein facilitates attachment


and entry into respiratory epithelia
2. Cell-cell spread of virus
3. No antibody protection: maternal Ab
and natural infection do not protect from
virus

1. Common cold with rhinorrhea (URT):


adults
2. Bronchiolitis (LRT): most important
viral cause in infants

Culture
RT-PCR
ELISA

Ribavarin
No vaccine

Pathogenesis
1. Hemagglutinin (HA) facilitates
attachment by binding to sialic acid
2. P proteins cleave cap from host mRNA
for capping of viral mRNA
3. RNA-dep RNA pol: facilitate synthesis
of progeny mRNA from pre-existing viral
mRNA
4. Infects URT then LRT (descending
infection
5. Cause damage to respiratory epithelia
6. IFN, NK and T cells facilitate
immune resolution
7. Neuraminidase (NA) facilitates viral
release and spread from infected cell
8. Could lead to influenza, primary viral
pneumonia, secondary bacterial infection
or post-infectious encephalitis

Influenza
1. Classic: malaise, headache,
myalgia, high fever, nonproductive cough
2. Asymptomatic to severe depending on
existing immunity and circulating strain
3. Children: high fever, croup, otitis
media
4. Usually self-limiting
5. Complications in
immunocompromised:
a. Primary viral pneumonia
b. Secondary bacterial infection
c. Post-infectious encephalitis
d. Guillen-Barre Syndrome
e. Myositis
f. Reyes syndrome: aspirin-associated

Culture
Hemadsorption
ELISA
Serology
RT-PCR

Amantadine &
rimantadine
(M2 protein)
Zanamivir &
Oseltamivir
(NA protein)
Vaccine
(formalininactivated):
contains
common
subtypes of
virus currently
in circulation

SARS (Severe Acute Respiratory


Syndrome)
1. Outbreak in South China and spread
throughout the world
2. Atypical Pneumonia: high fever,
chills, rigors, headache, dizziness, cough
3. Gastroenteritis: present in 20% of
patients (adults or children)

Serology
PCR

No treatment

Virulence
1. Antigenic Drift: mutation in genes
encoding HA or NA; error prone RNAdependent RNA polymerase; both
influenza A & B exhibit this
2. Antigenic Shift: reassortment of
genomic segments (H1N1 to H3N2);
causes pandemic due to novelty and lack
of immunity; only influenza A

Coronavirus
(Coronaviridae)

Helical
SS+ nonsegmented

Spread: respiratory
Location: respiratory
tract, GIT
Risk Factors:
1. H/O exposure to
place with
coronavirus

*Antigenic shift occurs due to


reassortment of influenza A viruses in
different species (swine, avian, horses)
1. Transmitted in respiratory droplets
from bodily fluids
2. Establish infection in RT and GIT
**MERS: Middle East Respiratory
Syndrome

RNA VIRUSES

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Rabies Virus

Helical
SS- non-segmented
Neurotropic
Bullet-shaped

Alphavirus

Helical
SS+ nonsegmented
Arbovirus
(arthropodborne)
Helical
SS+ nonsegmented
Congenital Disease
One serotype

(Rhabdoviridae)

(Togaviridae)

Rubella Virus
(Togaviridae)

Flavivirus
(Flaviviridae)

Helical
SS+ nonsegmented
Arbovirus
Over 60 serotypes

Spread: saliva from


animal
Location: peripheral
nerves
Risk Factors:
1. Unvaccinated
animals
2. Bats, raccoons,
skunks
At Risk:
1. Vets and animal
handlers
2. Person bitten by
rabid animal
3. Inhabitants of
countries with no
pet vacc.
Spread: mosquito
bite (Culex)

Pathogenesis
1. Bite of an animal transfers saliva to
human victim.
2. Ascending infection via peripheral
nerves to brain
3. Massive viral replication in the brain
4. Descending infection to salivary glands,
cornea, skin and muscles

Rabies
Stages:
1. Incubation: 60-365 days after bite
(depends on location); asymptomatic
2. Prodrome: fever, nausea, vomiting,
lethargy; pain on site of bite; virus
reaches CNS and multiplies; 2-10 days
3. Neurologic: hydrophobia (severe
pain upon drinking); pharyngeal spasms,
anxiety, hyperactivity, depression; CNS
symptoms arise: confusion, delirium,
paralysis; 2-7 days
4. Coma: cardiac arrest, hypotension,
hypoventilation
5. Death

Negri bodies!!
DFA: viral Ag
RT-PCR
ELISA

Post-exposure
prophylaxis:
virus travels
slow
Immediate
wound
cleansing:
KMNO4 and
antiseptics
Active and
passive
immunization

1. Mosquito bite introduces virus to


human.
2. Viremia: spread to target organs

Rise in Ab titers

Control of
mosquito
population

Spread: respiratory
Location: RT
Risk Factors:
1. Unvaccinated
2. Crowded
conditions
At Risk:
1. Children
2. Adults
3. Neonates
Spread: mosquito
or tick bite
(Aedes or Culex)
Location:
macrophages

1. Respiratory secretions of an infected


person is the only mode of transmission
2. Viremia: spread from lungs to liver,
spleen, LN
3. No cytopathic effect
4. CMI limits infection; Ab helps

1. Acute Encephalitis: Eastern and


Western equine encephalitis v.
2. Acute arthropathy: Chikungunya v.
3. Febrile illness: Venezuelan equine
encephalitis v.
WEE, EEE, VEE
1. German Measles: descending
maculopapular rash that starts from the
face; occipital lymphadenopathy; more
severe in adults with arthritis
2. Congenital Rubella Syndrome:
virus replicates in placenta and spread to
fetal blood; teratogenic effect; depending
on tropism and stage of development;
cataracts, deafness, hepatitis, CHD
and CNS deficits
1. Dengue Fever: breakbone fever;
transmitted by Aedes mosquito; high
fever, headache, rash, back and bone
pain
2. Dengue Shock syndrome & Dengue
Hemorrhagic fever: occur on rechallenge
by other dengue fever strains
3. Encephalitis: SLE, WNV, JE

RT-PCR
Serology
Blueberry
muffin baby

MMR vaccine
No treatment

Mosquito cell
line
RT-PCR
ELISA

Control of
mosquito
population

Pathogenesis
1. Mosquito bite introduces virus to
human.
2. Viremia: spread to target organs
Virulence
1. Cytolytic
2. Non-neutralizing Ab: can enhance
infection via Fc receptors on macrophages
by stimulating phagocytosis activation
of memory T cells

Other Medically Important RNA Viruses


Human Metapneumovirus RSV-like; cause bronchiolitis
Nipah and Hendra virus fruit bat reservoir; flu-like symptoms, possible complications with seizures and coma
Filoviridae Ebola/Marburg hemorrhagic fever often fatal!
Bunyavirus (Hantavirus) hemorrhagic fever; Hantavirus Respiratory Syndrome: death within 10 days
Arenavirus lymphocytic choriomeningitis virus; Lassa fever encephalitis

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