Respiratory and Gastrointestinal Viruses

Joseph B.
Ancla, RMT • De La Salle Medical and Health Sciences Institute • College of Medical Laboratory Science
Outline
• Respiratory Viruses and Gastrointestinal Viruses
✓ General Properties
✓ Pathogenesis
✓ Clinical Findings and Laboratory Diagnosis
✓ Epidemiology and Immunity
✓ Treatment, Prevention and Control
Respiratory and Gastrointestinal Viruses | 2

Pentamer
• Single-strand positive sense Myristate

(VP1)
RNA (infectious form)
Canyon
Pore
• Icosahedral symmetry (VP2)
• pH: unstable below a pH of 5.0 Protomer
6.0
Structure of Typical Picornavirus

• Temperature: thermostable Pentamer
Myristate
• Culture: WI-38 and MRC-5 cell (VP1)

Canyon
lines Pore
(VP2)
• Grow best at 33 °C
Protomer
• More than 150 serotypes are

known

M
^ RHINOVIRUS ^
intercellular adhesion low-density lipoprotein
MAJOR RECEPTOR MINOR RECEPTOR
© ©
molecule-1 (ICAM-1) receptor (LDLR)

Pathogenesis
• Viral Entry: upper respiratory

tract.
• Replication: surface epithelium

of the nasal mucosa.
• It cannot infect the lower The Respiratory System

respiratory system.

• Incubation Period: 2-4 days
• Acute illness: last for 7 days
• Symptoms: sneezing, nasal

obstruction, nasal discharge,
and sore throat; headache, mild
cough, malaise, and a chilly
sensation.
• Secondary bacterial infection

are common
• Antibody develops 7-21 days after infection

• Widely distributed
• Transmission: respiratory
transmission, hand-to-hand,
hand-to-eye, hand-to-object
• Infection rates are highest

among infants and children.

Treatment and Control
• No specific prevention method or

treatment is available.
• Unavailable vaccine
1. difficulty in growing
rhinoviruses to high titer in
culture
2. fleeting immunity
3. multiplicity of serotypes
causing colds.

Nucleocapsid protein (N) Membrane
glycoprotein (M)
• + ssRNA viruses
• helical capsids
Spike
• envelope: form crown-like protein (S)
(corona-crown) halos around

the capsids; budding into ER
Envelope
and Golgi. protein (E)
• Virion: Spherical, 120-160 nm

in diameter.
Structure of Coronavirus

Classification
mm
CORONAVIRUS
OC43 strain
229E strain
Respiratory and
Gastrointestinal Viruses | 14
Pathogenesis
• Tropism for epithelial cells of the respiratory or gastrointestinal tract.
• Virus enters the body via upper respiratory tract.

Bats Palm civets Humans
(amplified host)
Transmission of Coronavirus to Humans
Coronavirus

1. Colds in Adults
• Same symptoms with rhinoviruses
• Incubation period: 2-5 days
2. Severe Acute Respiratory Syndrome

• Incubation period: 6 days
_ f
• Early
sympto
ms:
fever,
malaise
, chills,
headac
V vfcx he,
dizziness, cough, and sore throat,
followed a few days later by shortness
of breath.

MER
•
•
S
Zoonotic virus
respiratory disease
C O R O N A
V I R U S
• Saudi Arabia in 2012
• Incubation Period: 2-4
days

• Immunity against the surface projection antigen is probably most
important for protection.
• Most patients (>95%) with SARS developed an antibody response to

viral antigens

nosis
• Antigen and Nucleic Acid Detection: ELISA and PCR (respiratory

secretions)
• Virus Isolation: Vero monkey kidney cells (OPS)
• Serology: ELISA, indirect immunofluorescent antibody assays, and

hemagglutination tests

Widely distributed all over the
world
Transmission: airborne or
contamination of frequently
touched surfaces (fomites)
Guangdong Province, People's

Republic of China, in November
2002
June 2003: 8460 cases of

SARS, 808 of them fatal.

Treatment, Prevention and Control
• No treatment for coronavirus

infections.
• SARS vaccines are under

development.
• Control: isolation of patients,

quarantine of those who had been
exposed, and travel restrictions, as
well as the use of gloves, gowns,
goggles, and respirators by health
care workers.

• Genome: negative-sense, Structure of Influenza Virus
single-stranded RNA,
segmented. Neuraminidase
M protein
• Helical nucleocapsid
• Envelope: Contains viral

HA and NA proteins ssRNA genome
(budding from PM)
• Virion: 80-120 nm in Hemagglutinin
diameter

• Replication: Nuclear Structure of Influenza Virus
transcription
Neuraminidase
• Temperature: can be M protein

stored at 0-4 °C
• pH: stable at acid pH

ssRNA genome
than alkaline pH
• Has 3 Antigenic forms

Hemagglutinin

eneraf
Tro
Influenza A
size size
Influenza B Influenza C
• antigenically ✓ composition ✓ composition
distinct NP antigenically
✓ structure ✓ structure
distinct NP
antigenic
specificity: virus absence of the
proteins & NA glycoprotein
glycoproteins

• Influenzavirus A: human and animal strains.
• Influenzavirus B: human strains.
• Influenzavirus C: humans and swine strains.
• Nomenclature: type, host of origin, geographic origin, strain number,

and year of isolation.
• Examples:
1. A/Hong Kong/03/68 (H3N2)

2. A/swine/Iowa/15/30 (H1N1).

Antigenic Variation
Pandemic
Epidemic
Pathogenesis
Red Blood Cell

Neuraminidase
M protein
ssRNA genome
Hemagglutinin Respiratory Cell

Pathogenesis
It poses a serious risk for elderly adults, very young children, and people
with underlying medical conditions:
1. Influenza
2. Pneumonia
3. Reye Syndrome

• Protection: IgA (nasal secretion), serum antibodies, and cell-mediated
immune response

nosis
• Polymerase Chain Reaction (PCR)
• Virus Isolation: Embryonated eggs and primary monkey kidney cells
• Serology: HI and enzyme-linked immunosorbent assay (ELISA)

Epi
• 1889: H2N2
• 1901: H3N8
• 1918: H1N1 “Spanish flu“-highly pathogenic strain-with high mortality
(estimated 21 million deaths worldwide)
• 1947: H1N11
• 1957: H2N2* “Asian flu“-illness but low mortality
• 1968: H3N2* “Hong Kong flu“-illness but low mortality
• 1977: H1N1*
• 1997: H5N1 (avian influenza pandemic; great risk for human
pandemic)
• 2009: H1N1*
1Notice also that some strains caused a second pandemic as a new unexposed population grows to adulthood.

Trevention andlreottment
• Amantadine hydrochloride and

Rimantadine: M2 ion channel
inhibitors
• Zanamivir and Oseltamivir
• Vaccines: Inactivated viral

vaccines

I U S
R
• Genome: negative sense, single- Large polymerase
stranded RNA, linear, non- SH Small

N Nucleocapsid
Phosphoprotein
RNP
hydrophobic
segmented. protein
M Matrix
protein
• Helical nucleocapsid
• Envelope: Viral glycoprotein HN and

fusion (F) glycoprotein (budding
from PM)
• Virion: Spherical, pleomorphic, 150 F Fusion protein

Lipid bilayer
nm in diameter HN Hemagglutinin V Multifunctional

neuraminidase zinc-binding protein
• Replication: Cytoplasm Structure of Paramyxovirus

Classification
Genus Example of Viruses

Respiroviruses Parainfluenza Virus 1 and 3
Rubulaviruses Parainfluenza Virus 2, 4a, 4b and Mumps
Morbilliviruses Measles Virus
Pneumoviruses Respiratory Syncytial Virus
Metapneumoviruses Human Metapneumovirus
Henipaviruses Nipah Virus (zoonotic virus)

cEOVIRlDAt
Genome: DS RNA in 11 segments
Symmetry: icosahedral
Covering: no envelope
Virion: 60-80 nm in diameter
Temperature: stable at 50 °C
pH: stable at pH 3.0-9.0

Inner capsid Core protein VP1 protein VP2
Structure of Rotavirus
Chemical: stable with lipid solvents
(ether and chloroform) but inactivated
by 95% ethanol, phenol and chlorine

ROTAVIRUS
A-E and 2 tentative species (F and G)
A-C infect humans

Pathogenesis
Enterotoxin
diarrheal disease
• Target: Villi of the small
intestine, multiplies in the
enterocytes and damage the
transport mechanisms.
• NSP4: induces secretion
• Viral excretion: 2-12 days
___ . _______ __ _________ ^

Cfinicaf Findings and Laboratory Diagnosis
• Rotaviruses: MAJOR diarrheal illness (acute gastroenteritis) in infants

and children worldwide but not in adults
• Incubation Period: 1 -3 days
• Symptoms: watery diarrhea, fever, abdominal pain, and vomiting,

leading to dehydration.
• PCR and ELISA for stool sample.

Epi demiofogy
gy nd I mmu ity
i ,
ni
a
• Ubiquitous in nature
• <5 years of age: Africa, Asia, Latin America
• Transmission: fecal-oral route
• Protection: Secretory IgA or interferon

• Supportive treatment: water and

electrolytes
• Wastewater treatment and

sanitation
• Vaccine: 2006: oral live attenuated

pentavalent human-bovine
reassortant rotavirus vaccine;
2008: oral live attenuated
monovalent human rotavirus
vaccine.
• Genome: Single-stranded RNA,
linear, positive-sense,
n
o
n
s
e
g
m
e
X-ray Structure of Norwalkvirus
n
t
ed
• Icosahedral capsid
• Envelope: None
• Virion: 27-40 nm in diameter.
• Replication: Cytoplasm

Cfinicaf Findings and Laboratory Diagnosis
• Noroviruses (Norwalk virus): viral

gastroenteritis in adults
• Incubation Period: 24-48 hours
Symptoms: diarrhea, nausea, vomiting, low-

grade fever, abdominal cramps, headache,
and malaise.
Complication: dehydration
Reverse transcriptase PCR (stool & vomitus)

or environmental samples (food and water)
ELISA for detecting antibodies

Epi demiofogy
gy nd I mmu ity
i ,
ni
a
• Human caliciviruses have worldwide distribution.
• Associated with epidemic outbreaks of waterborne, foodborne, and

shellfish-associated gastroenteritis
• Transmission: foodborne or person-to-person transmission via fomites

or aerosolization of contaminated body fluids (vomitus, fecal material).
• Antibodies against norovirus develops by 4 years of age.

• Prevention:
1. proper handwashing
2. proper stool disposal
3. disinfection of soiled areas
4. proper processing of foods
5. education of food handlers
6. purification of drinking water and
swimming pool water
• No available vaccine.

Generaf properties and
Classification
• Genome: Double-stranded DNA,

linear, infectious.
• Envelope: None
• Virion: Icosahedral, 70-90 nm in

diameter
• Replication: Nucleus Structure of Adenovirus

• Genus Mastadenovirus: Human Adenovirus (Groups: A-F)

Pathogenesis
• Target: infect and replicate in

epithelial cells.
• Most human adenoviruses

replicate in intestinal epithelium.
ADENOVIRUS

• Adenoviruses are responsible for 5% of acute respiratory disease in
young children; can also cause eye infection and GI disease.
• Associated with infantile gastroenteritis in young children and present in

diarrheal stools.

mmunity
• Maternal antibodies protect infants against severe adenovirus

respiratory infections.
• Neutralizing antibodies: detected in >50% of infants 6-11 months old.
• Healthy adults: antibodies to several types.

nosis
• Samples: stool or urine or from a throat, conjunctival, or rectal swab.
• Virus Isolation: Primary human embryonic kidney cells; other cell lines:
HEp-2, HeLa, and KB cell lines
• PCR for diagnosis of adenovirus infections.
• Serology: Complement fixation test, neutralization or hemagglutination-

inhibition tests

Epi
• Adenoviruses exist in all parts of the world.
• Respiratory types (1,2, 3, 5, and 7)
• Gastroenteritis types (40 and 41)

Treatment, Prevention and Control
• No specific treatment for adenovirus infections.
• Careful hand washing is the easiest way to prevent infections
• Environmental surfaces can be disinfected with sodium hypochlorite

• Chlorination of swimming pools and waste water to avoid waterborne
outbreaks.
• Vaccine: Oral live adenovirus vaccine containing types 4 and 7

• Genus: Enterovirus
• Genome: RNA

• Temperature: inactivated when
heated at 55 °C for 30 minutes.
• Chemical reaction: inactivated

by chlorine

Pathogenesis
• Viral Entry: mouth
• Multiplication: oropharynx or intestine.
• The virus may be found in the blood and CNS may be invaded by way of
the circulating blood.
• Spreads along axons of peripheral nerves to CNS then progress to lower

motor neuron to increasingly involve the spinal cord or the brain;
Destruction of nerve cells will result to change in peripheral nerve and
voluntary muscles.

• Poliovirus can cause poliomyelitis
• Incubation Period: 7-14 days but it may range from 3-35 days
Disease Characterized by
Manifestation
Mild Disease
fever, malaise, drowsiness, headache, nausea,
vomiting, constipation, and sore throat
Nonparalytic stiffness and pain in the back and neck (last
Poliomyelitis 2-10 days)
Paralytic Poliomyelitis
flaccid paralysis resulting from lower motor
neuron damage.
• Progressive Postpoliomyelitis Muscle Atrophy

mmunity
• Passive immunity from mother to off-spring is common
• Virus neutralizing antibodies provides protection against poliovirus.

nosis
• Throat and Rectal swabs or stool samples.
• Virus Isolation: human or monkey cells
• PCR Assay for identification of virus

Epi
• Poliomyelitis has had three epidemiologic phases: endemic, epidemic,

and the vaccine era.
• The disease occurs in all age groups.
• Human is the only known reservoir of infection

Global Eradication
• Started in 1988 by WHO
✓ 1994 - America
✓ 2000 - Western Pacific Region
✓ 2002 - Europe
• Endemic Polio - Afghanistan, India, Nigeria, and Pakistan

Prevention and Control
• Oral live polio vaccine and killed-virus vaccines are available.

Joseph B. Ancla, RMT • De La Salle Medical and Health Sciences Institute • College of Medical Laboratory Science

Respiratory and Gastrointestinal Viruses

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Joseph B.

• Respiratory Viruses and Gastrointestinal Viruses

✓ Clinical Findings and Laboratory Diagnosis

✓ Epidemiology and Immunity

✓ Treatment, Prevention and Control

Respiratory and Gastrointestinal Viruses | 2

• Single-strand positive sense Myristate

• Icosahedral symmetry (VP2)

• pH: unstable below a pH of 5.0 Protomer

Structure of Typical Picornavirus

Respiratory and Gastrointestinal Viruses | 4

• Culture: WI-38 and MRC-5 cell (VP1)

• More than 150 serotypes are

Structure of Typical Picornavirus

Respiratory and Gastrointestinal Viruses | 5

Respiratory and Gastrointestinal Viruses | 6

• Viral Entry: upper respiratory

• Replication: surface epithelium

• It cannot infect the lower The Respiratory System

Respiratory and Gastrointestinal Viruses | 7

• Acute illness: last for 7 days

• Symptoms: sneezing, nasal

• Secondary bacterial infection

Respiratory and Gastrointestinal Viruses | 9

• Infection rates are highest

Respiratory and Gastrointestinal Viruses | 10

• No specific prevention method or

Respiratory and Gastrointestinal Viruses | 11

• envelope: form crown-like protein (S)

(corona-crown) halos around

• Virion: Spherical, 120-160 nm

Respiratory and Gastrointestinal Viruses | 13

• Tropism for epithelial cells of the respiratory or gastrointestinal tract.

• Virus enters the body via upper respiratory tract.

Respiratory and Gastrointestinal Viruses | 15

• Same symptoms with rhinoviruses

• Incubation period: 2-5 days

2. Severe Acute Respiratory Syndrome

Respiratory and Gastrointestinal Viruses | 17

Respiratory and Gastrointestinal Viruses | 18

• Most patients (>95%) with SARS developed an antibody response to

Respiratory and Gastrointestinal Viruses | 19

• Antigen and Nucleic Acid Detection: ELISA and PCR (respiratory

• Virus Isolation: Vero monkey kidney cells (OPS)

• Serology: ELISA, indirect immunofluorescent antibody assays, and

Respiratory and Gastrointestinal Viruses | 20

Guangdong Province, People's

June 2003: 8460 cases of

Respiratory and Gastrointestinal Viruses | 21

• No treatment for coronavirus

• SARS vaccines are under

• Control: isolation of patients,

Respiratory and Gastrointestinal Viruses | 22

• Envelope: Contains viral

(budding from PM)

• Virion: 80-120 nm in Hemagglutinin

Respiratory and Gastrointestinal Viruses | 24

• Temperature: can be M protein

• pH: stable at acid pH

• Has 3 Antigenic forms

Respiratory and Gastrointestinal Viruses | 25

Respiratory and Gastrointestinal Viruses | 26

• Nomenclature: type, host of origin, geographic origin, strain number,

1. A/Hong Kong/03/68 (H3N2)

_ . _ _______ ^