RNA VIRUS

RNA VIRUS
January 25, 2018
Double stranded rna virus
 REOVIRIDAE
• Reoviruses were first isolated in respiratory and enteric specimens
• which they gained their name (Respiratory-Enteric-Orphan virus)
• Genus associated with human disease:
• Rotavirus
• Coltivirus
 Rotavirus
• Rotavirus are the most common cause of viral gastroenteritis in
infants and children. A major cause of infant mortality.
• Rotaviruses are naked viruses about 75 nm in diameter, with two
protein layers surrounding the capsid.
• Have a worldwide distribution and causes 600 000 deaths annually.
• Most outbreaks occur in winter months.
• Rotavirus is spread through oral-fecal route
• Incubation period: 1-4 days
• Replicates in the epithelial cells of microvilli of the small intestine.
• The microvilli is stunted and adsorption is reduced causing diarrhea.
Clinical Features
• Includes sudden
• Vomiting
• Diarrhea
• Can cause rapid loss of fluids and fatal dehydration
• Fever
• Abdominal pain
• Respiratory symptoms
 Diagnosis
• Difficult to culture
• Electron Microscopy
• May show wheel-like appearance
• ELISA and Latex Agglutination test
• Fecal samples are used
treatment
• Vaccines
• Rotateq
• Rotarix
Coltivirus
• Consists of the Colorado tick fever virus
• An arbovirus
• Vector: Dermacentor andersoni
• May develop a dengue-like infection
• Biphasic fever with a rash
• Children may experience hemorrhagic fever.
ARENAVIRIDAE
 Family: Arenaviridae
• Are enveloped, single stranded RNA

• Name derived from Latin word “arena”, which means “sandy”

• Due to grainy appearance in cross section

• Zoonotic: causes asymptomatic infection to rodents.

Family: Arenaviridae
• 29 named viruses; atleast 7 pathogenic to humans
Divided into 2 groups:
• Old World (LCMV-LASV complex)
• Lymphocytic Choriomeningitis Virus(LCMV)
• Lassa Virus (LASV)- most well known
• New World (Tacaribe Complex)
• Junin, Machupo, Guanarito, Sabia and Prital
 Transmission
• Each virus is associated with a particular rodent host
• Old world: rodents
• New world: bats

• Transmission to humans is by
• inhalation of aerosols
• Ingestion of contaminated food
• Direct contact of skin abrasions with infected urine
 Clinical Characteristics

Incubation Period: 10-14 days

• LCMV infection
• Causes influenza like-illness,
25% of patients develops meningitis.

Associated with house mouse (Mus muculus)

 Clinical Characteristics
• LASV infection
• Manifests fever, headache, pharyngitis,
myalgia and diarrhea.
Some patients develop hypotension,
hemorrhage and pleural effusion

Associated with multimammate rat (Mastomys

natalensis)
Diagnosis
• Serologic
• ELISA: detect arise in titers (IgG and IgM
antibodies)
Treatment and Prevention
• LCM(Lymphocytic Choriomeningitis)
• Supportive Treatment

• Lassa Fever
• Ribavirin therapy and immune plasma

• Prevention
• No vaccine available
• Avoid contact with virus, rodent control
RHABDOVIRIDAE
 Family: Rhabdoviridae
• Enveloped, helical, single stranded RNA virus
• Bullet-shaped capsid

• One member causes disease to human:

• RABIES virus
• Genus: LYSSAVIRUS

• Zoonotic: (warm-blooded animals) dogs, cats,

foxes, skanks
 Epidemiology
• Dogs are implicated in 99% of human rabies deaths.
• Global distribution: all mammals
• Endemic in dogs in Asia, Africa,
• India
• 17,000 deaths/year
• Philippines
• canine rabies 25,000 /yr

• Transmission: bitten or scratched by rabid animals.

Pathogenesis
• Bites/ Virus enters local tissue

• Travels along sensory nerves to CNS

* Virus multiplies in CNS neurons
(Hippocampus and cerebellum)

• Viremia

• Infects other organs

Clinical Characteristics
• Virus replicates locally at the wound site for a few days.
Incubation period:
usually 4-6 weeks.
but may vary from a week to years.
Severe head/neck bites: 2 weeks

(Migration by nerve axons to CNS)

 Clinical Characteristics
•Once symptoms develop, there is a rapid
progression to death over 1-2 weeks.
• Prodrome:
• vague flulike symptoms (fever, headache, sore throat, fatigue, nausea )
• painful sensitive nerves (tingling or twitching) at the bite area
 Clinical Characteristics
• CNS changes: (brainstem infection)
• Neurologic or Furious type (80%)
• Hyperactivity(anxiety, agitation, running, biting)
• Spasm of pharyngeal muscles in attempt of drinking
liquids(hydrophobia)
• Inability to swallow saliva and “foaming mouth”
• Paralytic or Dumb type (20%)
• Paralysis
• Respiratory and cardiac abnormalities
• COMA
• Begins within 10days of onset

• DEATH
• Secondary to respiratory dysfunction
• 1 reported case of recovery from active rabies
 Diagnosis
• Fluorescent Antibody Testing
• Gold standard for rabies diagnosis
• Rapid and sensitive
• Tissue samples: brain stem, hippocampus, cerebellum
• PCR
• DNA amplificaton
• Serology
• Serum Rapid Fluorescent Focus Inhibition Test (RFFIT)
• Histology
• Negri bodies: round cytoplasmic inclusions
Treatment
• If bitten with suspected rabid animal:

1.Wash bite - soap, water, alcohol, lavage with Iodine.

2. Inject hyper immune serum around skin of bite area
3. Vaccinate immediately with rounds of injection.
4. If symptoms develop. Death very likely treatment is typically
supportive.
Control and Prevention
• Vaccination of domestic animals
• Avoiding contact with rabid animals
FILOVIRUS

• Filo is a latin word meaning “filament” or “thread like”

describes the filamentous morphology as seen in
Electron Microscopy.
• 2 identified members:
• Ebola Virus
• Marburg Virus
Named after the location of first outbreaks
Filovirus
• Known to be associated with monkeys and fruit bats.
• Infection to humans is deadly
• Considered as most pathogenic of the hemorrhagic fever viruses.
• Mode of Transmission:
• Direct contact with body fluids
Filovirus
• Ebola and Marburg virus infection
• Severe hemorrhages, vomiting, abdominal pain, myalgia,
pharyngitis, and conjunctivitis
• Case fatality rates are expected with Ebola virus infection.
Diagnosis
• ELISA and RT-PCR
• Electron Microscopy
• Demonstration of characteristic morphology
Control and Treatment
• No known effective anti-viral therapy. Only supportive

• Patients must be isolated in special containment facilities

• Strict compliance of protective clothing
• Use of Biosafety Level IV Cabinet
ARBOVIRUSES
ARBOVIRUSES

Arthropod Borne Viruses

are viruses transmitted to man by arthropod vectors.
(Exc. Rubivirus causing rubella and Hantavirus)

Belong to Three(3) Families:

1. Togaviridae: E.g. EEE, WEE, NEE
2. Bunyaviridae: Sandly Fever, Rift Valley Fever
3. Flaviviridae: Yellow Fever, Dengue Fever, Japanese Encephalitis
 Transmission Cycle
• Man - arthropod -man
• e.g. dengue, urban yellow fever.
• Reservoir may be in either man or arthropod vector.
• Animal - arthropod vector - man
• e.g. Japanese encephalitis, EEE, WEE, jungle yellow fever.
• The reservoir is in an animal.
• Both cycles may be seen with some arboviruses such as yellow
fever.
Man-Arthropod-Man Cycle
Animal-Arthropod-Man Cycle
Diseases Caused

• Fever and rash - this is usually a non-specific

illness resembling a number of other viral illnesses
such as influenza, rubella, and enterovirus
infections. The patients may go on to develop
encephalitis or haemorrhagic fever.
• Encephalitis - e.g. EEE, WEE, St Louis
encephalitis, Japanese encephalitis.
• Haemorrhagic fever - e.g. yellow fever, dengue,
Crimean-Congo haemorrhagic fever.
Diagnosis

• Serology - usually used to make a diagnosis of

arbovirus infections.
• Culture - a number of cell lines may be used,
including mosquito cell lines.
• Direct detection tests - e.g detection of antigen and
nucleic acids
Prevention

• Surveillance - of disease and vector populations

• Control of vector - pesticides, elimination of breeding
grounds
• Personal protection - screening of houses, bed nets, insect
repellants
• Vaccination - available for a number of arboviral infections
e.g. Yellow fever, Japanese encephalitis
Bunyavirus

• are arboviruses, except for Hantavirus which is a

rodent-borne virus.

• Most of the members causes febrile illness,

hemorrhagic fever and encephalitis
 MEMBERS
Bunyavirus
targets brain and liver causing
Rift Valley fever virus
encephalitis and hepatitis

Encephalitis; usually develops

LaCrosse virus(LACV) in summer referred as “summer
cold/flu”
California encephalitis
Encephalitis
virus

Crimean-Congo
infects vascular endothelium
hemorrhagic
and liver
fever(CCHF) virus
Bunyavirus

• Genus: Hantavirus
• transmitted through aerosolized rodents excreta
• Members causes
• Hemorrhagic fever and Kidney disease
• Hantaan virus
• Seoul
• Puumala
• Dobrava
• *Sin nombre, with acute respiratory failure. Referred as
Hantan Pulmonary Syndome (HPS)
Bunyavirus
• Hantan Pulmonary Syndrome
• 3-5 day febrile syndrome, followed by
• Hypotensive shock and pulmonary edema
• Severe cases, may develop DIC.
• 50% mortality rate

• Treatment: supportive
Flavivirus

• Contains a number of important human pathogens

• Japanese encephalitis virus
• St. Louis encephalitis virus
• West Nile Virus
• Yellow fever virus
• Dengue virus
Arthropod vector; usually mosquito
• Hepatitis C virus: nonarbovirus
Flavivirus

• Japanese Encephalitis Virus

• First discovered and originally restricted to Japan. Now
large scale epidemic.
• Major cause of encephalitis in Asia
• Most common cause of arboviral encephalitis in the world
• Human infections are subclinical
• In clinical cases, ranges from influenza like illness to
encephalitis
Flavivirus

• St. Louis Encephalitis virus

• Most common flavivirus infection in the US

• Symptomatic infection develops fever only, whereas some

develop meningoencephalitis.

• Milder in children than adults

• Vector: bird biting Culex mosquitoes.

Flavivirus

• West Nile Virus

• Transmits infection to humans by mosquito vector from
natural reservoir, birds.
• Causes mild flu-like illness (west nile fever)
• May be invasive causing encephalitis.
Flavivirus
• Yellow Fever
• 2 Major forms:
• Jungle : natural reservoir; among primates
Vector, A. aegypti mosquito
• Urban : humans serves as the reservoir when bitten by infected mosquito

• An outbreak to workers during construction of Panama Canal.

Flavivirus

• Yellow Fever virus

• Yellow Fever virus primarily infects the liver, resulting in
fever, jaundice and hemorrhage.

• Diagnosis is usually made by serology

• There is no specific antiviral treatment
• An effective live attenuated vaccine is available
• used for persons living in or traveling to endemic areas
• Dengue Virus
• Has four serotypes, 1 through 4.
• each serotype causes Dengue Fever, a milder form of infection.
• Subsequent infection with one of the other three remaining serotypes increase risk of
developing severe dengue, Dengue Hemorrhagic Fever.
Flavivirus

• Dengue virus
• Most common cause of arbovirus disease in the world.
• Causes 2 distinct type of diseases
• Classic dengue fever: 10M cases
• Dengue Hemorrhagic Fever (DHF): 500, 000 of cases, with 5%
mortality
• Transmitted by female Aedes mosquitoes, A. aegypti and A.
albopictus.
• Classic Dengue Fever
• Severe fever, headache, myalgia, and jointpain (referred also as “breakbone
fever”)
• Some patients develop rash
• Self limiting and resolved in 1-2 weeks.
• Dengue Hemorrhagic Fever
• Develop symptoms of classic DF, along with
• Thrombocytopenia
• Hemorrhage
• Shock
Potentially leads to death with complications due to plasma
leaking, fluid accumulation, severe bleeding, respiratory
distress.
Diagnosis
• Serology
• Antibody detection
• NS1 detection
• RT-PCR
• Primary tool to detect early course of illness
Treatment and Prevention
• Main method of control
• Mosquito eradication

• No specific treatment
• To severe dengue, maintenance of the patients body fluid volume is
critical.
Immunization
• One dengue vaccine has been registered (2016) by Sanofi Pasteur,
DENGVAXIA
• A live attenuated tetravalent vaccine.
Togavirus

• 2 members causing disease to humans:

• Alpha viruses – mosquito borne, causes fever,
encephalitis causing altered level of consciousness.
• Rubivirus – causes rubella
Togavirus
• Alpha viruses
• Infects birds, rodents and humans
• 3 main viruses named after geographic regions:
• EEE: Eastern equine encephalitis (Eastern US)
• WEE: Western equine encephalitis (Western US)
• VEE: Venezuelan equine encephalitis (Southern US)
Togavirus

• Rubivirus
• Not an arbovirus; causes disease to humans only
• Causative agent of RUBELLA, a mild febrile illness with a
rash
• Ability to cross placenta(TORCH)
• Causes terrible congenital defects, esp. in first trimester
 Rubivirus
• Rubella “German Measles”
• Mild measles-like illness
• Like measles,
• contracted by respiratory secretions
• prodrome of fever and flu symptoms
• Followed by red maculopapular rash, spreads from face >> torso >>
extremities
• Unlike measles,
• Patients are less sick
• Complications such as encephalitis does not occur
• Rash lasts only for 3 days, not 6. Thus its other name “3 day measles”
• Rubella-induced congenital infection
• Greatest early in fetal development (1st trimester)
• Embryo cells demonstrate chromosomal breakage and
inhibition of mitosis

Classical Triad
1. Cataract
2. Cardiac abnormalities
3. Deafness
• Immunity to Rubella
• Antibodies appears as rash fades
• Rash in association with detection of IgM indicates
recent infection
• IgG persists for life
• Immune mothers transfer antibodies to offspring and
protected for 4-6 months
Diagnosis

• Clinical diagnosis is unreliable

• Isolation
• Rabbit Kidney cells (RK13)
• Vero cells
• Serologic Tests
• Hemagglutination Inhibition
• ELISA
Prevention and Treatment

• No specific treatment
• Vaccine is available
• Live and attenuated
• Given to children at 15 mos of age as part of MMR
immunization program.
PARAMYXOVIRIDAE
CHILDHOOD FEVER VIRUSES
RESPIRATORY VIRUSES
PARAMYXOVIRIDAE
• Includes many pathogenic viruses, especially for young children
• MEASLES VIRUS
• MUMPS VIRUS
• Respiratory Syncytial Virus
• Parainfluenza Virus
Recently discovered
• Human Metapneumovirus
• Nipah Virus
Paramyxoviruses
• Members possess:
• Hemagglutinin(H), Neuraminidase(N) and Fusion(F) protein
• HN: viral adhesion molecule
• F: responsible for the fusion of the virus to the cell and one of infected cell to
another infected cell.
 MUMPS VIRUS

• Enveloped with HN and F surface antigens

• Transmitted by droplets of infected saliva

• Replicates in the
• UPPER RESPIRATORY TRACT >> REGIONAL LYMPH NODES >>
DISTANT ORGANS (Parotid Gland/Salivary Gland is frequently
involved)
 MUMPS
• Flu-like symptoms, over next few days
• Classic mumps symptoms
• Painful and swollen parotid gland (PAROTITIS or
BEKE)
• Dry mouth
• Trouble swallowing
• 25% of affected males, develop orchitis,
inflammation of the testes
• Females may develop oophoritis
 Diagnosis

• Clinical diagnosis
• Viral isolation
• Vero cells
• LLC-MK2 cells
Treatment and Prevention

• No antiviral therapy available

• Supportive treatment

• Vaccine available (MMR)

 MEASLES VIRUS

• Enveloped with H and F protein in the surface

• Highly contagious spreads by aerosol

• Replicates in the
• RESPIRATORY MUCUOUS MEMBRANES >> CONJUNCTIVAL
MEMBRANES >> DISTANT ORGANS
 MEASLES “RUBEOLA”

• PRODROME
• HIGH FEVER
• CONJUNCTIVITIS
• RHINITIS
• KOPLIK SPOTS: day or 2 before rash
• Small red-based lesions with bluish white speck in the oral
mucosa
• RASH
• Maculopapular rash, face >> neck >> torso >> feet
 MEASLES
• Complications
• Eye damage

• Myocarditis

• Encephalitis, rare but 10% of patients die.

In severe cases, may develop Subacute Sclerosing

Panencephalitis (SSPE), a slow form of encephalitis.
Diagnosis
• Clinically diagnosed

• Isolation
• PMK cells; forms distinctive spindle-shaped or multinucleated cells.
 Treatment and Prevention
• No antiviral therapy
• Supportive treatment

• Vaccine available and recommended to children (MMR) measles-

mumps-rubella
PARAMYXOVIRIDAE
• Includes many pathogenic viruses, especially for young children
• MEASLES VIRUS
• MUMPS VIRUS
• Parainfluenza Virus
• Respiratory Syncytial Virus
Recently discovered
• Human Metapneumovirus
• Nipah Virus
 Parainfluenza Virus

• 3 surface antigens: H, N and F

• Important pathogen in children,

causing croup and other respiratory
diseases.
 Parainfluenza Virus
• Has 4 types (PIV 1 through 4)
• PIV-1 and PIV-2: causes most serious illness in children
• PIV-1: primary cause of croup (laryngotracheobronchitis) in children.
• Swelling of structures causes narrowing of airway causing a wheezing
sound and barking cough.
• PIV-3: bronchiolitis and pneumonia in infant. (2nd in
importance to RSV)
• PIV-4: mild upper respiratory tract infections
 Parainfluenza Virus

• MOT: aerosol inhalation, respiratory secretions

• Targets respiratory tract cells causing inflammation

• RHINITIS
• PHARYNGITIS
• LARYNGOTRACHEITIS
• BRONCHIOLITIS
 Parainfluenza
• Diagnosis
• Isolation
• PMK cells
• LLK-MK2 cells

• Direct Examination
• Immunofluorescence: more rapid
• Prevention and Treatment
• Patients may be given with aerosolized ribavirin to treat infection.

• No vaccine available
 Respiratory Syncytial Virus

• Lacks both H and N surface proteins

• Contain surface protein F
• Mediates host cell fusion into syncytial cells, which is a
hallmark of RSV infection.

• Most common viral cause of pneumonia in children,

especially infants less than 6 months of age.
RSV- syncytium
formation

Immunofluoresent stain
 Respiratory Syncytial Virus

• Diseases
• Colds: runny nose, cough, fever
• Croup
• Bronchitis
• Pneumonia
• Spreads through large particle droplets and contact
with fomites
• Highly contagious with outbreaks during winter and
spring. (seasonal)
Diagnosis

• Cell culture
• HEp-2 cells
• Forming syncytia
• PMK cells
• Human Diploid fetal cells
RSV identification using: IFA, EIA, serum neutralization
tests.
Treatment and Prevention

• Approved treatment
• Ribavirin therapy
• Passive Immunization
• Palivizumab
• A monoclonal antibody produced by recombinant DNA method
• Preexposure prophylaxis to susceptible patients
• RSV immune globulin

• No vaccine available
 Human Metapneumovirus

• Closely related to RSV

• Displays clinical symptoms related with RSV, influenza,
PIV
• Causes
• bronchiolitis and pneumonia in infants
• Lower respiratory tract disease in adults
• Seasonal
• Noted to have cause outbreaks during winter
Diagnosis
• Difficult to grow in cell culture
• Grows slowly in standard cell culture lines
• Monkey kidney
• A549

• RT-PCR and IFA

• Currently being used for identification
 Nipah Virus
• Causes
• respiratory disease in pigs
• Febrile acute encephalitis in humans
• Result from direct contact with diseased pigs

• Reservoir: fruit bats

• Intermediate hosts: Pigs and other animals
ORTHOMYXOVIRIDAE
ORTHOMYXOVIRIDAE

• Members are the INFLUENZA VIRUSES

• Distinguished using two major structural protein
• Matrix protein
• Nucleoprotein
(Influenza A, B and C)
• Further classified into subtypes using the two major surface
glycoproteins
• Hemagglutinin
• Neuraminidase
Eg. Influenza AH1N1, AH3N2
 ORTHOMYXOVIRUSES
HA - hemagglutinin

NA - neuraminidase

8 RNA segments, put together with a

protein (NUCLEOPROTEIN)

lipid bilayer membrane

M1 protein: anchors HA and NA

spikes to the lipid bilayer
membrance
type A, B, C : NP, M1 protein
sub-types: HA or NA protein
 SURFACE GLYCOPROTEINS

Haemagglutinin (HA) Neuraminadase (NA)

• Hemagglutinin glycoprotein is the viral •Cleaves and disrupts neuraminic

attachment protein and fusion protein (sialic) acid from cell
•Neuraminic acid is an important
•Attaches to host sialic acid receptors, component of mucin, the substance
present on that covers the mucosal epithelial cells
•upper respiratory tract, causing •Important in releasing mature
invasion and infection virus from cells
•Red blood cells, causing to
agglutinate when mixed with RBCs -
hence the nomenclature
 CLASSIFICATION
➢Type A viruses cause the most cases of
influenza in humans
➢ Also infects other mammals(swine, avian, etc)
➢Type B viruses are endemic in USA and
associated with local epidemics
➢Type C viruses rarely cause disease

Type B and C, were isolated from humans only.

No animal reservoir
 Antigenic Variation

• Influenza viruses are unique because of their ability to

alter antigenic (H and N) composition
• High in type A influenza virus
• RNP and Matrix proteins are stable
• 2 types:
• ANTIGENIC DRIFT
• ANTIGENIC SHIFT
 ANTIGENIC DRIFT
Minor but gradual mutation in antigenic structure
allowing hemagglutinin to escape neutralizing
antibodies.

GRADUAL ANTIGENIC CHANGE

WITHOUT A CHANGE IN SUBTYPE
H3N2 H3N2 H3N2 H3N2
1968 1975 1993 2004
HONG VICTORI BEJIN FUJIA
KONG A G N
 Antigenic drift

➢Can involve
any antigenic
protein
➢Can occur
every year
➢REQUIRES
NEW
VACCINE
 Antigenic shift
➢Abrupt and drastic major change resulting to new
either H or N antigens
➢2 mechanisms by gene reassortment after
simultaneous infection of a cell with two different
strains

• Associated only to Influenza A

• 3 major shifts in the history
Influenza A Influenza A
Influenza A (H3N2)
(H1N1)
(H2N2) “Hongkong Flu”
“Spanish “Asian Flu” 1968
Flu”
1957-1958
1918-1919
Mechanisms of Influenza Virus Antigenic “Shift”

15 HAs
9 NAs Non-human Human
virus virus

Reassortant
virus
 Epidemiology

➢MOT:
➢large droplets (sneezing,
coughing, contact with saliva)
➢18-72 HR INCUBATION
 SYMPTOMS

➢FEVER
➢HEADACHE
➢MYALGIA
➢COUGH
➢RHINITIS
➢OCULAR SYMPTOMS
➢CHILLS and/or SWEATS
Infection may be very mild, even asymptomatic,
moderate or very severe
 Complications

➢Infected individual predisposed

to bacterial infections –
➢Staphylococcus aureus,
➢Streptococcus pneumoniae
➢Other complications –
➢Reye’s Syndrome
 Laboratory Diagnosis

• Virus isolation
• embryonated eggs
• primary monkey kidney
• canine kidney cells
• Hemagglutination (inhibition)
• Serology
Four-fold or greater increase in
hemagglutination inhibition antibody titers over
2 weeks.
 Prevention and Treatment

70-90% effective in preventing illness

➢ RIMANTADINE and AMANTADINE
➢Prevents uncoating of virus
➢ZANAMIVIR (inhaled) and OSELTAMIVIR (oral)
➢Neuraminidase inhibitors
➢Shorten the course of Influenza A and B
CORONAVIRIDAE
Coronavirus

• Prefix corona- is used because

of the crownlike surface
projections seen in EM
 Coronavirus
• Causes
• Respiratory illness
• Common cold: 15% of cases
2nd most common cause of Colds.
• Pneumonia to adults
• Severe Acute Respiratory Syndrome
• Small percentage causes diarrhea to children
Severe Acute Respiratory Syndrome (SARS)

• New infectious disease emerged in

Hongkong(2002) became pandemic after
6month period.
• Caused by novel coronavirus (SARS-CoV) of
• animal origin horseshoe bat(reservoir) and civet
cat(intermediate host)
• Transmitted by respiratory and fecal routes
• Fever, chills, and body aches which usually
progressed to pneumonia.
• Cause of death is lung failure(severe respiratory
distress
• MERS-CoV (Middle East Respiratory Syndrome
Coronavirus)
• New emerging pathogen
• First reported in 2012 in Saudi Arabia
• Patients developed severe acute respiratory illness,
fever, cough and shortness of breath.
 Coronavirus
• Diagnosis
• Fragile and difficult to culture
• Direct detection method
• Immunofluorescene
• EIA
• Electron Microscopy: stool as specimens
• Nucleic acid based detection
• RT-PCR: most common diagnostic approach
 PICORNAVIRIDAE
ONE OF THE LARGEST FAMILIES, WITH 230 MEMBERS.
PICORNAVIRIDAE

• Picornaviruses derived from Italian word piccolo

meaning small.
• 2 Genera with human clinical significance:
• Rhinovirus
• Enterovirus, have 5 subgroups
• Poliovirus
• Coxsackie A and B
• New enterovirus
• Parechovirus
• Hepatitis A
Rhinovirus

• Acid labile, sensitive to pH less than 6.

• More than 100 serotypes exists
• Resistant to detergents, lipid solvents, and extreme
temperature
• Optimum growth occurs between 33 and 34 degree
celcius.
Rhinovirus

• MAJOR CAUSE OF COMMON COLD.

• Most people experience cold 2-3 times a year, 50% is
caused by Rhinoviruses
• Incidence increased during cold climates.
• Colds:
• Profuse watery discharge
• nasal congestion
• Sneezing
• Headache
• sorethroat and cough.
Rhinovirus

• Rhinoviruses are transmitted to

susceptible individuals by:
• Direct contact of contaminated
surfaces/fomites
• Aerosol particles

• Higher incident rates occur in humid,

crowded conditions, especially during
cooler months.
Diagnosis
• Clinical diagnosis
• Cell culture
• Grows best exclusively at lower temperatures 30 degree celcius
• Cell lines:
• MRC5
• W138
Treatment and Prevention
• No specific treatment for common cold
• Only supportive(antihistamines, nasal decongestant, nasal sprays)

• No vaccine available

• Prevent transmission by
• E.g handwashing, proper hygiene
Enterovirus

• Enteroviruses are a genus of the picornavirus family which

replicate mainly in the gut.
• Unlike rhinoviruses, they are stable in acid pH.
• At least 71 serotypes are known: divided into 5 groups
• Polioviruses
• Coxsackie A viruses
• Coxsackie B viruses
• Echoviruses
• New Enteroviruses
Epidemiology

• World-wide in distribution
• Non-polio enteroviruses have marked summer and
fall seasonality in temperate zones
• Spread person-person, by houseflies, wastewater and
sewage
• Humans only significant natural reservoir
Pathogenesis
Minor
viremia
Mouth
Gut- lymphatics
Lymph node
Virus

CNS Heart Skin Lung Eye Bloodstream

Major viremia
 Poliovirus

• Has the ability to infect cells:

• Peyer’s patches of the intestine
• Motor neurons
• Cause of Poliomyelitis
• 3 serotypes: 1, 2 and 3
Epidemiology

• Humans are the natural reservoir

• More common in infants and young children, but risk of
paralytic disease increases with age
• Improved hygiene- older kids affected
• Increased paralytic disease
• Epidemic 1950s
Pathogenesis

• The incubation period: 7 - 14 days.

• Following ingestion,
• the virus multiplies in the oropharyngeal and intestinal
mucosa.
• the tonsils and the Peyer's patches of the ileum are invaded
and the virus enters the blood resulting in a transient viraemia.
• In a minority of cases, the virus may involve the CNS
following dissemination.
Clinical Features

• Subclinical infection (90 - 95%)

• account for the vast majority of poliovirus infections.
• Abortive infection (4 - 8%)
• a minor influenza-like illness occurs, may be accompanied
by aseptic meningitis
• recovery occurs within a few days
• Major illness (1 - 2%)
• the major illness may present 2 - 3 days following the minor
illness or without any preceding minor illness.
• Signs of aseptic meningitis are common.
• Involvement of the anterior horn cells lead to flaccid paralysis.
• Involvement of the medulla may lead to respiratory paralysis and
death.
Treatment and Prevention

No specific antiviral therapy is available. However the

disease may be prevented through vaccination. There
are two vaccines available.
• Intramuscular Poliovirus Vaccine (IPV)
• Developed by Jonas Salk
• consists of formalin inactivated virus
• Oral Poliovirus Vaccine (OPV)
• Developed by Albert Sabin
• Consists of live attenuated virus
• Taken orally and may shed in the feces
Coxsackie, Echoviruses & New Enteroviruses

• The remaining member of Enterovirus, all can

cause:
• Asymptomatic or mild febrile illness
• Respiratory symptoms (eg. Cold)
• Rashes
• Aseptic meningitis
Coxsackie Viruses

• They are divided into 2 groups based on the

lesions observed in suckling mice
• Coxsackie A
• causes paralysis and death of the mouse
with extensive skeletal muscle necrosis.
• also causes
• Herpangina
• Hand foot mouth disease
• Coxsackie B
• causes less severe infection in mice but
multiple organs can be damaged, such as
heart, brain, liver, pancreas, and skeletal
muscle
• Also causes
• Pleurodynia also called Bornholm disease.
• Myocarditis
• Pericarditis
Echoviruses

• The first echoviruses were accidentally discovered

in human faeces, unassociated with human disease
during epidemiological studies of polioviruses.
• The viruses were named echoviruses (enteric,
cytopathic, human, orphan viruses).
New Enteroviruses

• 4 new enteroviruses have been identified (68 - 72).

• Enterovirus 70 is the causative agent epidemics of acute
haemorrhagic conjunctivitis that swept through Africa, Asia,
India and Europe.
• Enterovirus 71 appears to be highly pathogenic and has been
associated with epidemics of aseptic meningitis, encephalitis,
paralytic poliomyelitis-like disease and hand-foot-mouth
disease.
Disease Associations (1)

• Paralytic Disease - most commonly associated with polioviruses

but other enteroviruses may also be responsible, notably
enterovirus 71
• Myocarditis - group B coxsackieviruses are the major cause of
• Rubelliform rashes - a rash disease resembling rubella may be seen
with several coxsackie A, B, and echoviruses.
• Conjunctivitis - associated with several types of enteroviruses,
notably Coxsackie A24 and Enterovirus 70 (haemorrhagic
conjunctivitis)
• Pancreatitis/Diabetes - associated with Coxsackie B virus infection.
The extent of the role of the virus in diabetes is unknown.
Laboratory Diagnosis

• Virus Isolation
• Mainstay of diagnosis of enterovirus infection
• Coxsackie A viruses cannot be easily isolated in cell
culture.
• RT-PCR –
• Currently being used for identification
 CALICIVIRIDAE
• Contains 2 genera that causes disease to humans:
• Saporovirus
• Norovirus, specifically Norwalk Virus
Are causative agents of human gastroenteritis.
Saporovirus
• Distinguished with a cup-shaped morphology
• Usually causes diarrhea and vomiting in infants and young children
• Originally discovered in Sapporo, Japan
Norwalk Virus

• Genus: Norovirus
• Named after an outbreak in Norwalk, Ohio,
elementary school.
• Most common cause of infectious gastroenteritis
in US.
• Caused outbreaks in schools, colleges, as well as on
cruise ships and resorts.
Norwalk Virus

• Transmission is through
• Foodborne; most common
• Waterborne
• Person-person contact
• Incubation period: 1-2 days
• Symptoms shows:
• Nausea
• Vomiting
• Diarrhea
Lasts for 1-3 days.
Diagnosis
• Cannot be grown in culture
• Reliable with
• Electron Microscopy
• RT-PCR
• Most commonly used diagnostic assay
• Stool is the best sample for detection of Norwalk virus.