Microbiology 3.10 DR.

SENGSON
RNA Viruses II SEPT 25, 2013

OBJECTIVES and children

1. What are the general characteristic of the virus family? (The rest of the
 Incubation period: 1-3 days
RNA viruses)
2. What are some of the important viruses of the family?
3. What type of diseases do these viruses cause? Clinical Manifestations:
4. What is the mode of transmission of the virus?  Acute onset of fever and vomiting  24-48hours later: watery
5. What is the epidemiology of the virus/disease? When and where should diarrhea
we be looking out for these? o Persists for 3-8 days
6. How do we diagnose the viral infection/disease? o Severe cases: dehydration, electrolyte abnormalities, and acidosis
7. How can the viral infection/disease be prevented, controlled, and/or
 Immunocompromised children: persistent infection and diarrhea can
treated?
develop
OUTLINE
I. Double Stranded: Segmented Non-Enveloped
a. Reoviridae
1. Rotavirus
II. Single Stranded: Positive Sense Non-Segmented Non-Enveloped
a. Picornaviridae
1. Enteroviruses
2. Rhinoviruses
3. Hepatitis A Virus
b. Hepeviridae
III. Single Stranded: Positive Sense Non-Segmented Enveloped
a. Coronaviridae
b. Togaviridae
1. Alphaviruses
2. Rubiviruses
3. Flaviviridae
c. Retroviridae
1. Human T-cell Lymphotropic Virus Type 1 (HTLV-I)
2. Lentivirus (HIV 1 & 2)

*SEE Appendix A for outline of RNA Viruses

Figure 1. Spectrum of Rotavirus Symptoms
DOUBLE STRANDED SEGMENTED: NON-ENVELOPED
REOVIRIDAE

Classification of Reovirus
 15 genera but only 4 of which are able to infect humans
1. Orthoreovirus – infect humans, birds, dogs
2. Rotavirus – agents of infantile diarrhea in human and animals
3. Orbivirus
4. Coltivirus – Colorado Tick fever virus

Pathogenesis

Figure 2. Skin Turgor

Treatment
 Supportive treatment for the gastroenteritis caused by rotavirus
 Oral or parenteral fluid and electrolytes – prevent dehydration, acidosis,
shock and death

Prevention
 Oral Rotavirus vaccine
 What can I do to protect my child from rotavirus?
o Vaccinate your child on time
o Talk with your child’s doctor if you have questions
ROTAVIRUS o Keep a record of your child’s vaccinations – to make sure your
 Rota “wheel” child is up-to-date
 3 distinct rotavirus group – A, B, C
 Disease results from direct or indirect contact with infected people via SINGLE STRANDED POSITIVE SENSE NON-SEGMENTED NON-ENVELOPED
feco-oral route PICORNAVIRIDAE
o Can also be found on toys and hard surfaces
 Spread in families and institutions are common  One of the smallest in terms of virion size
o Most common cause of healthcare-associated diarrheas in infants  Non-enveloped and spherical

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 MICROBIOLOGY 3.10

 Composed of a protein shell surrounding the naked RNA genome

 Icosahedral capsid consists of polypeptides, VP1, VP2, VP3 and VP4
 VP4 is located on the internal side of the capsid
 Contains 9 genera, including Enterovirus, Rhinovirus and Hepatovirus.

Figure 3. Picornaviridae

ENTEROVIRUSES
A. Nonpoliovirus Infections
Figure 5. Hand, Foot and Mouth Disease
 Coxsackie A and B
 Echovirus

Figure 6. Herpangina: Coxsackie viruses

Management
Figure 4. Echovirus  Supportive
 IVIG - for chronic enteroviral encephalitis in immunodeficient patients,
Etiology and Epidemiology life-threatening neonatal infections, suspected viral myocarditis, and
 >90 distinct serotypes enterovirus 71 CNS disease.
 Humans are the only known reservoir  Cohorting of infected neonates.
 Spread by  Standard and contact precautions.
o fecal-oral  Hand hygiene, disinfection of surfaces.
o respiratory routes
 Chlorination treatment of drinking water in swimming pools.
o from mother to infant in the peripartum period
o May survive on environmental surfaces for periods long enough to
B. Poliovirus Infections
allow transmission from fomites
 Viral shedding
o Fecalweeks to month
o Respiratory 1-3 weeks
 Incubation period: 3 to 6 days
o for acute hemorrhagic conjunctivitis 24-72 hours

Clinical Manifestations
 In young infants: nonspecific febrile illness
 Respiratory: coryza (aka: cold), pharyngitis, herpangina, stomatitis,
pneumonia, pleurodynia
 Skin: exanthem (hand, foot and mouth)
 Hand, foot and mouth disease: (remember this!)
o enterovirus 71, coxsackievirus A16
 Neurologic: aseptic meningitis, encephalitis, motor paralysis
 GIT: vomiting, diarrhea, hepatitis, pancreatitis
 GUT: orchitis
 Eye: acute hemorrhagic conjunctivitis, uveitis
o coxsackievirus A24 variant and enterovirus 70
 Heart/Muscle: myocarditis, myositis, pleurodynia
o coxsackievirus B1 to B5
 Patients with humoral and combined immunodeficiencies can have
persistent CNS infections and/or a dermatomyositis-like syndrome
Figure 7. Poliomyelitis
 3 serotypes: 1, 2, 3
 Occur only in humans
 Spread by fecal-oral and respiratory route
 Communicability is greatest shortly before and after onset of clinical
illness when the virus is present in the throat
 Virus persists in the throat for approx. 1 week and several months in
feces
 Excreted in high concentrations in feces
o Patients are contagious as long as fecal excretion persists
 Incubation period:
o Nonparalytic poliomyelitis: 3 –6days

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 MICROBIOLOGY 3.10

o Paralytic poliomyelitis: 7 –21 days o Self-inoculation by contaminated secretions on hands

Clinical Manifestations
 72% asymptomatic
 24 % non-specific signs & symptoms
 1-5% Aseptic meningitis with paresthesias
o <1% presents with:
 Rapid onset of asymmetric acute flaccid paralysis with
areflexia of the involved limb
 Residual paralytic disease involving the motor neurons
(paralytic poliomyelitis)
 Cranial nerve involvement
 Paralysis of respiratory tract muscles
Diagnosis and Treatment
 Viral culture or PCR
o Ideally done within 14 days of onset
o Specimens: pharynx, feces, urine & CSF (rarely)
o Highest yield in stools
o ≥ 2 stool or throat swab specimens should be obtained at least 24
hrs apart from patients with suspected paralytic poliomyelitis as
early as possible in the course of the illness
 Treatment: supportive
Prevention
 Polio Vaccines
o Given for 3 doses at 2, 4 & 6 mos. of age
o Inactivated poliovirus vaccine (IPV)
 given subcutaneous or intramuscular
 Part of DPT-IPV-Hib combination vaccine
o Oral poliovirus vaccine (OPV)
 the vaccine of choice for global eradication
o Both highly immunogenic and effective
o Immunity is prolonged, perhaps lifelong
 No anti-viral drugs available for treatment with poliovirus infection.
o Aerosol spread
 Infections occur throughout the year
 Multiple serotypes circulate simultaneously
o prevalent serotypes circulating change from season to season
 Increased viral shedding during first 2-3 days
 By adulthood, antibodies to many serotypes have developed
Diagnosis & Treatment
 Viral cultures from secretions
 PCR
 Treatment: Supportive
HEPATITIS A VIRUS (HAV)
 Under the genus Hepatovirus of the Picornaviridae
 Only one serotype is known
 Transmission is via feco-oral route
 Acute, self-limited illness with fever, malaise, jaundice, anorexia, and
nausea
 Most infectious during 1-2 weeks before onset of jaundice or elevation
of liver enzymes
 Destroyed by autoclaving (121°C for 20 min), boiling (in water for 5
mins.), dry heat, ultraviolet irradiation, treatment with formalin and
chlorine
Figure 9. Icteric sclerae

RHINOVIRUSES Risk Factors

 These are the common cold viruses  Close contact with HAV infected person
 Most commonly recovered agents from people with mild upper  International travel
respiratory illnesses  Household/personal contact
o with a child who attends a daycare center
Etiology o with newly arriving international adoptee
 Most frequent cause of common cold or rhinosinusitis  Recognized food outbreak
 Approx. 100 antigenic serotypes identified  Men having sex with men (MSM)
 Infection with one type confers some type-specific immunity but of  Use of illegal drugs
variable and brief duration
o Offers little protection against other serotypes
 Incubation period: 2-3 days, up to 7 days

Figure 8. Rhinovirus

Epidemiology
 Transmission occurs by: Figure 10. Hepatitis A facts
o Person-to-person contact

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 MICROBIOLOGY 3.10
Diagnosis and Treatment
 Serology: anti-HAV IgM and IgG
o (+) anti-HAV IgM = current or recent infection
o (+) anti-HAV IgG and (-) IgM = past infection or immunity
 Treatment: supportive
Control Measures
 Hepatitis A Immunoglobulin
o Given intramuscular within 2 weeks after exposure to HAV
o >85% effective in preventing symptomatic infection
 Hepatitis A vaccine
o given intramuscular, 2-dose schedule
o Highly immunogenic
o ≅ 94-100% protective efficacy in clinical HAV prevention
HEPEVIRIDAE
 Only 1 serotype
 Where Hepatitis E virus belongs
 Feco-oral or water-borne transmission
 Non-enveloped with icosahedral virion
 Causes acute illness
o Jaundice, malaise, fever, abdominal pain and arthralgia
 Have zoonotic hosts (swine)
 Diagnosis: (+) anti-HEV IgM & IgG
 Treatment: supportive
SINGLE STRANDED POSITIVE SENSE NON-SEGMENTED ENVELOPED
CORONAVIRIDAE
 Large, enveloped RNA viruses
 virion: spherical, 120-160nm in diameter; helical nucleocaspid (9-11nm
in diameter)
 proteins: 2 glycoproteins and 1 phosphoprotein
rd
o (some with 3 glycoprotein: hemagglutinin esterase)
 distinctive club-shaped surface projections
o giving the appearance of a solor corona to the virion
 The entire cycle of coronavirus replication takes place in the cytoplasm
o nucleocaspids develop in the cytoplasm and mature by budding
into cytoplasmic vesicles like ER and Golgi
 have narrow host ranges
 Genome: 27-32kb in size, capped, and polyadenylated
 Resemble orthomyxoviruses but have petal-shaped surface projections,
arranged in a fringe
Figure 11. Coronavirus in microscopic photo and schematic diagram
 2 Genera:
o Coronavirus
 Causative agent of Severe Acute Respiratory Syndrome (SARS)
 Also causes avian infectious bronchitis virus
 Two strains of human coronavirus: 229E and OC43
 Those among rodents and domestic animals are included
in these 2 strains
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 transmission: via respiratory droplets; also fomites and
contact
 most infectious stage: 10 days after symptoms begins
o Toroviruses
 among animals and widespread among ungulates
 cause gastroenteritis
Properties
 exhibit a high frequency of mutation during each round of replication
o high incidence of deletion mutation;
o undergo a high frequency of recombination during replication
 this is unusual for an RNA virus with a non-segmented
genome
o this property may contribute to the evolution of new virus strain
Symptoms
 infections limited to the upper respiratory tract (“colds”)
 usually afebrile in adults
 most display tropism for epithelial cells of the respiratory and GIT
 acute respiratory tract signs include:
o coryza, nasal congestion, sneezing, and sore throat
Sudden Acute Respiratory Syndrome (SARS)
 First identified in Nov. 2002, Guangdong, China
 Serious respiratory illness  pneumonia and
progressive respiratory failure
 Most probably originated in a nonhuman host and
acquired the ability to infect humans
Pathogenesis:
a. virus attaches to receptors on target cells by their glycoprotein spikes
on the viral envelope
o (HcoV-229E receptor is aminopeptidase N while the SARS virus
receptor is ACE-2)
b. Internalized by absorptive endocytosis
c. The S-glycoprotein causes fusion of the viral envelope
d. Uncoating
e. Viral genomic translation
o Produces a virus-specific RNA-dependent RNA polymerase
f. Transcription of full-length complementary RNA by the RNA polymerase
o Serves as a template for a nested set of 5 – 7 subgenomic mRNAs
g. Synthesis of new genomic RNA molecules
h. Interaction of newly synthesized genomic RNA molecules with the
nucleocaspid protein to form helical nucleocaspids (occurs in the
cytoplasm
i. Budding of nucleocaspids through vesicles
j. Maturation
k. Mature virions are transported to periphery
l. Exit or wait until the cell dies
Diagnosis
 Isolation
o in SARS - from oropharyngeal specimens and grown in Vero
Monkey kidney cells
 Antigen detection - ELISA test of respiratory secretions
 Serology - easier than viral isolation
o paired sera, acute and convalescent
 PCR of respiratory secretions between day 4-8 of infection
Epidemiology
 distributed worldwide; major cause of respiratory illness among adults
during the cold season
 MERS-CoV: (Middle East Respiratory Syndrome Coronavirus)
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 MICROBIOLOGY 3.10

o first reported in Saudi Arabia in 2012

o severe acute respiratory illness
 fever, cough, and shortness of breath
 half of the patients died
o spread through close contact
Treatment, Prevention, & Control
 no proven treatment and vaccine
 control among health workers (gloves, gowns, goggles/masks)
 quarantine of exposed people
 travel restrictions
TOGAVIRIDAE
 have lipid-containing envelope (70nm) and are rather sensitive
 9.7-11.8 kb in size
 mature by budding from host cell membranes
ALPHAVIRUSES
 nucleocaspid has 42 capsomeres
 11-12 kb in size
 3 or 4 major structural polypeptides, 2 glycolysated
 cytoplasmic replication
 assembly: budding through host cell membranes
Classification
1. Alphaviruses causing encephalitis
a. Eastern Equine encephalitis (EEE) – Aedes, Culex
b. Western Equine encephalitis (WEE) - Culex tarsalis mosquito
c. Venezuelan Equine encephalitis (VEE) – Aedes, Psorophora, Culex
2. Alphaviruses causing fever, rash and polyarthritis
a. Chinkungunya
 Makonde term “that which bends up”- a symptom of arthralgia
 vectors: Aedes aegypti, A. albopictus, Culex fatigans
 hosts: replicate in wide range of vertebrates
 s/sx: benign, dengue-like syndrome but in shorter duration
(fever, arthralgia, maculopapular rash, leukopenia)
 diagnosis: IgM antibodies through ELISA, four-fold increase in
antibodies in paired sera, PCR and viral isolation
 treatment: supportive and antipyretics and bed rest
b. Mayaro virus
c. O'nyong-nyong
d. Sindbis
e. Ross River virus
f. Semliki Forest virus
Pathogenesis
a. Infection to humans is initiated by the bite of an infected mosquito
b. Viral replication occurs in the midgut epithelium
c. In susceptible vertebrate hosts: multiply in myeloid and lymphoid cells
or in vascular endothelium
d. The virus that crosses the blood-brain-barrier through cerebral vascular
channels can infect nerve cells (neuronal degeneration occurs in
arbovirus-induced encephalitides)
Clinical Findings
e. Incubation period: 4-21 days
 Inapparent infections are common
 Some develop mild flu-like illness, whereas others develop encephalitis
(encephalitis: sudden onset of severe headache, chills and fever,
nausea and vomiting, generalized pains and malaise)
 Fever may last 4-10 days
 Within 24-48 hrs – drowsiness – stupor
 Severe cases mental confusion, tremors, convulsions and coma
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LABORATORY CRITERIA FOR CONFIRMATION
Cases of arboviral disease are classified according to the
following laboratory criteria:
Probable result
 Virus-specific IgM antibodies in CSF or serum
detected by antibody-capture EIA, but with no other
testing in the same or later specimen.
Confirmed result:
 Isolation of virus from or demonstration of specific
viral antigen or nucleic acid in tissue, blood, CSF, or
other body fluid, OR
 Fourfold or greater change in virus-specific
quantitative antibody titers between acute (within 2
weeks after onset date) and convalescent sample (2-4
weeks after onset date), OR
 Virus-specific immunoglobulin M (IgM) antibodies in
CSF or serum by antibody-capture enzyme
immunoassay (Capture EIA) AND confirmed by
demonstration of virus specific neutralizing
antibodies in the same or later specimen.
RUBIVIRUSES
Figure 12. Rubella (German Measles)
 Causes 3-day measles
 Relatively mild illness but cause increase in morbidity in fetus of
infected mother
 Has no arthropod vector
 Currently classified into 2 distantly related groups (clades) and 9
genotypes
 Transmission: droplet secretions from infected (direct contact with
infected persons, usually children 5-14 y/o); contact from surfaces
contaminated with secretions
 incubation period: 14 days
Properties
 sole member and is not transmitted by arthropods
 not transmitted by arthropods
Immunologic Properties
 Only a single antigenic type
 Antibodies develop during incubation period of the disease (as the rash
fades)
 Maximal titer during early convalescence and persists for years
Pathogenesis
a. entry of the virus through the mucosa of the upper respiratory tract
b. initial replication in respiratory tract
c. multiplication in cervical lymph nodes
d. viremia develops 7-9 days and lasts until the appearance of the rash
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 MICROBIOLOGY 3.10

e. development of antibody coincide with the appearance of rash the infection because it is not given early enough to prevent
viremia; significant side-effects in adults: arthralgia and
Clinical Manifestations arthritis

FLAVIVIRIDAE
 Dengue virus, Japanese encephalitis virus, Hepatitis C virus

Classification
A. Genus Flavivirus
1. Tick-borne viruses
a. Mammalian tick-borne group (15)
 Tick-borne encephalitis virus, European subtype (TBEV-
Eu)
o prevalent in western, northern, central and eastern
parts of Europe;
 Tick-borne encephalitis virus, Far Eastern subtype
(TBEV-FE)
o occurs in eastern parts of the Russian Federation, in
CONGENITAL RUBELLA SYNDROME China and Japan;
 Maternal viremia during pregnancy result in infection of the b. Seabird tick-borne group (4)
placenta and fetus  Tyuleniy virus
 Damage involves tissues of all germ layers 2. Mosquito-borne viruses
 Results from combination of rapid cell death of some cells a. Aroa virus group (4)
and persistent viral infection in others  Aroa virus
 The continued infection frequently induces chromosomal b. Dengue virus group (5)
aberrations and finally reduced cell division  Dengue virus, types-1 to 4 (DENV-1 to DENV-4)
 The earlier in pregnancy the infection occurs, the greater c. Japanese encephalitis group (10)
the damage to the fetus.  Japanese encephalitis virus (JEV)
 The infant infected during the first trimester may be  West Nile virus (WNV)
stillborn d. Yellow fever virus group (9)
o If it survives, it may have deafness, cataracts, cardiac  Yellow fever virus (YFV)
abnormalities, microcephaly, motor deficits or other B. Genus Pestivirus
congenital anomalies (85%) 1. Bovine viral diarrheavirus 1 (BVDV-1), four serotypes
o In addition there is thrombocytopenic purpura, 2. Bovine viral diarrheavirus 2 (BVDV-2), two serotypes
hepatosplenomegaly, icterus, anemia and low birth 3. Border disease virus, two serotypes
weight 4. Classical swine fever virus (CSFV), four serotypes
 Maternal IgG is transferred to the fetus and lost within 5. Pestivirusof giraffe (unclassified)
6months C. Genus Hepacivirus
 Fetus synthesizes IgM 1. Hepatitis C virus (HCV), six genotypes
o Demonstration of rubella antibodies of the IgM class D. Unclassified (2)
in infants is diagnostic of congenital rubella. 1. GB virus A (GBV-A)
o IgM antibodies are not able to cross the placenta 2. GBV-A-like viruses
3. GB virus C (GBV-C)
4. Hepatitis G virus (HGV)
Diagnosis
 isolation of virus from nasal or throat specimens in tissue culture or PCR DENGUE FEVER, DENGUE HEMORRHAGIC FEVER AND DENGUE SHOCK
 Serology (detection of antibodies) SYNDROME
a. (+) specific Rubella IgM at birth; or  Dengue Fever
b. Four-fold increase IgG in paired sera of infant and mother o 4 serotypes that causes human disease:
 need to repeat collection at 1-2 weeks apart  DEN-1, DEN-2, DEN-3, and DEN-4
o Acute febrile illness syndrome
Management and Prevention o Caused by several arthropod-borne viruses
 Isolation and contact precautions should be exercised in babies with o Characterized by:
congenital rubella (contagious since viral shedding is equal to 1 year)  Fever
 monitor serially and regularly for development of complications  Myalgia or arthralgia
 Prevention: live-attenuated MMR vaccine  Rash
o recommended for > 12 months,  Leukopenia
 2 doses, SC  Lymphadenopathy
 begins at 12 months, then booster at 4-6 years
 Induces lifelong immunity in at least 95% of recipients);  Dengue Hemorrhagic Fever/Dengue Shock Syndrome
o for adolescents and adults, especially women of child-bearing age o Acute vascular syndrome + abnormal hemostasis
 reduces the incidence of congenital rubella syndrome o Liver is palpable
 IVIG injected into the mother in the first 3-4 months of st
o 1 Phase:
laboratory-proved rubella does not protect the fetus against  Acute vascular syndrome + abnormal hemostasis
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 MICROBIOLOGY 3.10
st
 1 phase: abrupt onset of fever, malaise, vomiting, headache, o Ascites
anorexia, and cough after 2-5 days o GI bleeding
 Rapid deterioration and physical collapse  Recovery Phase
o Median day of admission to the hospital after onset of fever is the o Altered level of consciousness
4th day. o Seizures
nd
o 2 phase: o Itching
 cold, clammy extremities, warm trunk, flushed face, and o Slow heart rate
diaphoresis
 Restless, irritable, complain of epigastric pain Course of Dengue Illness
 Scattered petechiae on the forehead and extremities,
spontaneous ecchymoses
 Easy bruisability and bleeding at sites of venipuncture
 Circumoral and peripheral cyanosis
 Rapid, labored respirations
 Weak, rapid, and/or thready pulses
 Faint heart sounds
 Narrow pulse pressure (<20mmHg)
o Key pathologic feature of DHF is increased vascular permeability
with plasma leakage into the interstitial spaces associated with
increased level of vasoactive cytokines
o Occur in individuals with passive acquired (as maternal antibody)
or due to a previous infection with a different serotype of virus.
 Initial symptoms simulate normal dengue but the patient’s
condition worsens.
o Immune complex type of hypersensitivity with marked
depression of complement components (particularly C3)
o Ag-Ab complexes activate the complement system with
subsequent release of vasoactive peptides
Figure 14. The course of Dengue Illness
Symptoms of Dengue Fever
 Within 4 days, there is high fever, which coincides with dehydration. In
the laboratory, hematocrit is high, amount of virus in the blood is high
as well.
 Critical period (day 4-7) – by the fever goes down, problem of shock
and bleeding reoccur. Platelet would also decrease.
 As patient gets well, platelet eventually increases as well as formation
of IgM and IgG.

Transmission
 Aedes aegypti
o daytime-biting mosquito is the principal vector
 Aedes albopticus
o day-and-night time biting mosquito
 Dengue viruses are transmitted during the feeding process
 highly domesticated, breeding in any container collecting fresh water
 Explosive transmission in urban areas (70 –80% population)
 Female mosquitos take repeated blood meals (great potency as vectors)
 Feeds preferentially on people
 Abundant in and around human habitations
 Breeds in clean, stagnant water

Figure 13. Symptoms of Dengue Fever

 Febrile phase
o Sudden onset fever
o Headache
o Mouth and nose bleeding
o Muscle and joint pains
o Vomiting
o Rash
o Diarrhea
 Critical Phase
o Hypotension
o Pleural effusion
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 MICROBIOLOGY 3.10

Criteria for Dengue

 Dengue with and without warning signs
 Severe Denge
 Please see appendix

Laboratory Studies
 Isolation of virus (culture)
 Serologic diagnosis depends on a four-fold or greater increase in
antibody titer by hemagluttination inhibition or ELISA
 Primary and secondary dengue virus infections
 Results in the production of dengue-reactive IgM or IgG antibodies

Prognosis
 Complete recovery eventually occurs
 Early diagnosis and aggressive fluid replacement therapy can reduce
fatality rates to <1%
 Immunity is type-specific (remember there are 4 serotpes), therefore
it is possible to contract dengue fever virus four times Figure 16. Life cycle of Flavivirus
 Antibody-dependent enhancement phenomenon: Previous infection
may predispose to more serious illness upon subsequent infection with ASEPTIC MENINGITIS OR ENCEPHALITIS
another serotype  Incubation period of 4-14 days
 Manifests non-specific symptoms
Prevention o Lethargy
 DOH’s Mag 4S Laban sa Dengue o Nausea
 Search and Destroy o Headache
o Clean environment from collected dirty water o Fever
 Self-protection Measures  Within 7 days, there will be alterations in behavior and motor
o Avoid wearing short outfits to avoid mosquito bites abnormalities, confusion and agitation, and increase unsteadiness.
nd
o Use insect repellant  In the 2 week, there will be convulsions, higher fever, alterations in
 Seek Early Consultation consciousness, hyperreflexia, expressionless facies, slurred speech,
o If fever persist for 2 days and rashes start appearing, go to your choreoathetosis
rd
physician for consultation.  By 3 week, fever eventually declines, neurologic symptoms gradually
 Say NO to Indiscriminate fogging improves
o But YES to fogging ONLY during outbreaks.  In fulminant infections, death may occur in first 5 days of illness.

JAPANESE ENCEPHALITIS VIRUS Diagnosis

 Exists as a single serotype
 Vector: Culex mosquito
o Usually infects large vertebrae animals
 Pigs are the most important source of viral amplification  maintains
sustained viremia
o Even infected, they produce offsprings. The offsprings will then
harbor the virus and eventually spread again.
 Birds are also responsible for the spread to new geographical areas
maintaining and amplifying Japanese encephalitis virus in the
environment
 Man is a dead-end host
 Prevalent among rural areas because Culex mosquito breeds in rice
paddies.
 (+) serum JE-specific IgM
 ELISA
(+) CSF IgM JE-specific
 Four-fold increase in titer between acute and convalescent-phase
serum by hemeagglutination inhibition (HAI)
Treatment, Prognosis, and Prevention
 Supportive
 Most recover with little sequelae
 Case-fatality rate: 10-35%
o Seen among young children, secondary to death due to infections
and CNS complications
 A vaccine is available (hopefully next year)
 Immunity is believed to be permanent after a single infection. Both
humor antibody and cellular immune responses are thought to be
th
important in protection and recovery from infection. (Jawetz, 25 ed.)

HEPACIVIRUS
 Aka Hepatitis C Virus
 Spread by parenteral exposure to blood of HVC-infected people
 Risk factors: injection drug use, multiple sexual partners, or having
received blood products before 1992
 Signs and symptoms are indistinguishable from signs of HAV or HBV
infections
 Risk of perinatal transmission (5-6%)
Figure 15. Culex mosquito
Causes of Hepatitis C
 Blood transfusions

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 MICROBIOLOGY 3.10

 Sharing of needles and other drug taking equipment Genes Required for Viral Replication
 Mother to baby transmission 1. Gag – encodes the core proteins (group specific)
 Body piercing 2. Pro – encodes the protease enzyme
 Tattooing 3. Pol – encodes the reverse transcriptase enzyme (polymerase)
 Unprotected sex with multiple partners 4. Env – encodes glycoproteins that form projections on the envelope of
the particle
Table. Prevalence of Anti-HCV in High Risk Groups in the Philippines (1995)
IV drug users 72%  Genes play a role in determining the diagnosis of this disease. (You
Hemodialysis patients 20% don’t need to memorize. -Dr. Sengson)
Multi-transfused patients 10%  Gene order in all retroviruses is 5’-gag-pro-pol-env-3!
Commercial sex workers 8%  Directly transforming retroviruses carry an onc gene!
Chronic liver disease 7%  Retroviruses that contain oncogenes are highly oncogenic!
Commercial blood donors 3-5%
HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-1 (HLTV-I)
Diagnosis  Latency Period: 10-30 years!
 All people with HCV-RNA in their blood are considered to be  Four types: HTLV-I, HTLV-II, HTLV-III, HTLV-IV
infectious
 Incubation period: 6-7 weeks Epidemiology
 HCV anti-IgG enzyme immunoassay  Originally isolated from leukemic cells of patients with aggressive forms
o (+) within 15 weeks after exposure and 5-6 weeks after onset of of T-cell malignancies from the US, Japan and Caribbean
hepatitis
o Infants born with HCV-positive mothers: passively acquired Transmission
maternal antibody may persist up to 18 months  Sexual
 PCR test  Parent to child through breast milk
o Detection of HCV-RNA in serum or plasma within 1-2 weeks after  Parenteral (blood)
exposure and before onset of symptoms
Clinical Manifestations
Treatment, Prognosis, and Prevention  Adult T-cell leukemia and lymphoma
 With advancing age, people with chronic HCV are at risk for developing o Associated with HTLV-I
chronic hepatitis cirrhosis and hepatocellular carcinoma o Rapidly fatal
 IFN- ɑ or pegIFN- ɑ with ribavirin: indicated for chronic HCV infection  Tropical Spastic Paraparesis (TSP)/ HTLV-I Associated Myelopathy
(HAM)
 All patients should be immunized against Hepatitis A and Hepatitis B
o Neurodegenerative syndrome
o Slowly indolent weakening of the legs  paraparesis or paraplegia
RETROVIRIDAE
 Replicate in a host cell by reverse transcription Pathogenesis
 Targets host cell as an obligate parasite
 Once inside the host cell cytoplasm, the virus uses its own reverse
transcriptase to produce DNA from its RNA genome (the reverse of the
usual pattern thus RETRO!)
 New DNA is incorporated into the host cell genome and exists as a
provirus
o Host cell treats the viral DNA as part of its own genome
o Translates & transcribes the viral genes along with the cell’s own
genes producing proteins required to assemble new copies of the
virus

Characteristics
 Capable to cause lifelong infections
 Evade usual mechanisms of immune clearance
 Produce chronic diseases in the host that manifests only after a long
asymptomatic period

Classification
1. Alpharetrovirus – avian Figure 17. Infected HTLV-I T cells will induce proliferation of CD4+ T cells.
2. Betaretrovirus – mouse Attempts by CD8+ T cells will be made to counter the infection. But due to
3. Gammaretrovirus – mammals some genomic mutations, infected cells can evade such mechanism; hence,
4. Deltaretrovirus (Human T-lymphotropic virus) the malignant expansion!
5. Epsilon retroviruses – fish
6. Spumavirus Diagnosis
7. Lentivirus (HIV)  Cytology
o Finding of malignant cells (mature T-cells with pleomorphic
irregular nuclei that express the helper T-cell marker CD4+)
 Serology (ELISA or RIA)
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 MICROBIOLOGY 3.10
o Positive results are confirmed using Western blot analysis to
detect antibodies against gp46 env and p19 and p24 gag-encoded
core proteins
 CD8+ T CELLS involvement
 Infection of monocytes/ macrophages
Figure 18, Confirmatory tests either identify or rule out the
presence of antibodies to distinct viral antigens (gag: p 19 or
p24; env: gp21 e; gp 46; gp61/68)
LENTIVIRUS - HIV 1 & 2
Epidemiology
 First identified in 1981
o Originated from cross-species infections by simian viruses in rural
Africa, probably due to direct human contact with infected
primate blood.
 Latent virus persists in peripheral blood mononuclear cells and cells of
brain, bone marrow, and genital tract (even when the plasma viral load
is undetectable!)
Mechanism of HIV-Induced Immunodeficiency
Transmission
 Sexual contact (vaginal, anal, or orogenital)
 Percutaneous blood exposure (from contaminated needles or other
sharp instruments)
 Mucous membrane exposure to contaminated blood or other body
fluids
 Mother-to-child transmission
o during pregnancy
o at labor and delivery
o postnatally through breastfeeding
 Transfusion with contaminated blood products
Pathogenicity
 HIV selectively infects CD4+ lymphocytes (The CD4 molecule itself
serves as the cellular receptor for HIV!)
 HIV also infects peripheral blood monocytes, monocytoid cell lines and
various forms of tissue macrophages (cell types that express CD4
molecule):
o follicular dendritic cells of lymph node germinal centers, skin and
thymus Langerhan’s cells and microgial cells in the brain
 Primary immunopathogenic lesion in HIV infection involves CD4+ T
cells
o critical dependence on the inducer/helper function of CD4+ T cells
o Defects are both quantitative and qualitative
o In advanced HIV disease: quantitative depletion of CD4+ T cells
Group 17 | Pedro, Pelayo, Pera, Peralta, Pereyra
o T cell dysfunction can be demonstrated in patients early in the
course of infection, even when the CD4+ T cell count is in the low-
normal range.
o There is an increase in the degree and spectrum of dysfunctions as
the disease progresses.
o One of the first abnormalities seen is a defect in response to
remote recall antigens, such as tetanus toxoid and influenza, at a
time when mononuclear cells can still respond normally to
mitogenic stimulation (CD4+ memory cells cannot recall the
antigens thus affecting the response of the antibody-producing B
cells, adversely affecting the immunity of HIV patients).
o Defects of central memory cells are a critical component of HIV
immunopathogenesis.
o Relative CD8+ T lymphocytosis (early phase) is associated with
high levels of HIV plasma viremia and reflects dysregulated
homeostasis.
o During the late stage HIV infection: significant reduction in the
numbers of CD8+ T cells despite the presence of high levels of
viremia.
o However, as the disease progresses, the functional capability of
these cells gradually decreases and may be lost entirely.
o Circulating monocytes are generally normal in number in HIV-
infected individuals.
o Monocytes express the CD4 molecule, thus are targets of HIV
infection.
o Degree of cytopathicity for monocyte-cell lineage is low, and HIV
can replicate extensively with relatively little cytopathic effect
 a role in the dissemination of HIV in the body
 serve as reservoirs of HIV infection, thus representing an
obstacle to the eradication of HIV by antiretroviral drugs.
o Tissue macrophages are an important source of HIV during the
inflammatory response associated with opportunistic infections.
o Infection of monocyte precursors in the bone marrow may directly
or indirectly be responsible for certain of the hematologic
abnormalities in HIV-infected individuals.
Infection of peripheral T-cell
infection of T-cell precursors
infection of tissue macrophages and dendritic cells
decreases functional capacity of existing peripheral T-lymphocytes and
antigen presenting cells
inhibits production and maturation of T-cell precursors
preventing the reconstitution of the peripheral T-cell pool
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 MICROBIOLOGY 3.10

Clinical Manifestations
 The immunodeficiency of AIDS relates to:
o a primary HIV-I induced T-cell deficiency
o a secondary dysfunction of B-cells with polyclonal
hypergammaglobulinemia and defective specific antibody
responses
o a defect in natural killer cell function

th
Figure 19. p24 antigens peak at about 6 week after the infection
th
until the 12 week (variable at this point). Antibody production is
able to lower the level of p24 antigens (latency for about 8-10
years) up until CD4+ T cells are depleted thus reducing the
stimulation of B cells to produce antibodies. By then, p2 antigens
start to rise again leading to the death of the patient. Some
patients have defects in producing the antibodies (genetic
problem) rendering them more susceptible to the cytopathic
effects of HIV (“malas malas lang minsan” – Dr.Sengson) Figure 20. Clinical Manifestation

Humoral Immune Response  Some Signs and Symptoms:

 Antibodies to HIV usually appear within 3–6 weeks and almost o Unexplained fevers , Generalized lymphadenopathy
invariably within 12 weeks of primary infection o Hepatomegaly, Splenomegaly
o Rare exceptions are individuals who have defects in the ability to o Failure to thrive
produce HIV-specific antibodies o Persistent or recurrent oral and diaper candidiasis
o Detection of these antibodies forms the basis of most diagnostic o Recurrent diarrhea
screening tests for HIV infection o Parotitis
 The appearance of HIV-binding antibodies detected by ELISA and o Hepatitis
Western blot assays occurs prior to the appearance of neutralizing o CNS disease
antibodies. The latter appear following the initial decreases in plasma o Lymphoid interstitial pneumonia
viremia  more closely related to the appearance of HIV-specific CD8+ o Recurrent invasive bacterial infections
T lymphocytes o Presence of Malignancies
 First antibodies detected are those directed against the 1. Kaposi’s sarcoma
immunodominant region of the envelope gp41  appearance of 2. Non-hodgkin’s lymphoma
antibodies to the structural or gag protein p24 and the gag precursor 3. Carcinoma of rectum and tongue
p55 o Presence of opportunistic infections
 Antibodies to p24 gag  appearance of antibodies to the outer 1. Pneumocystis jiroveci (pneumonia)
envelope glycoprotein (gp120), the gag protein p17, and the products 2. Cytomegalovirus
of the polgene (p31 and p66) 2. Atypical mycobacteria
3. Toxoplasma gondii
Diagnosis and Monitoring 4. Candida albicans
 Screening by ELISA or RIA and confirmed by Western Blot assay 5. Herpes simplex
o depends on (+)antibodies to HIV and/or the direct detection of HIV 6. Cryptococcus neoformans
or one of its components 7. Cryptosporidium
o Antibodies to HIV generally appear in the circulation 3–12 weeks
following infection Prognosis
 CD4+ T cell count is the best indicator of the immediate state of  Development of opportunistic infections (Pneumocystis jirovecii
immunologic competence of the patient with HIV infection. pneumonia [PCP])
 Patients with:  Progressive neurologic disease
o CD4+ T cell counts <200/L are at high risk of disease from P.  Severe wasting
jiroveci  In the absence of treatment, infants infected perinatally and with
o CD4+ T cell counts <50/L are at high risk of disease from CMV, o High viral loads (> 100,000 copies/mL)
mycobacteria of the M. aviumcomplex (MAC), and/or T. gondii o Markedly decreased CD4+ T-lymphocyte counts
 Patients with HIV infection should have CD4+ T cell measurements o CD4+ percentage < 15%
st
performed at the time of diagnosis and every 3–6 months thereafter o Symptoms developing during the 1 6 months of life
o frequent measurements should be made if a declining trend is
noted

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 MICROBIOLOGY 3.10

Treatment

ADDITIONAL INFORMATION FROM DOH (Epidemiology):

http://www.doh.gov.ph/sites/default/files/NEC_HIV_June-AIDSreg2013.pdf

SUMMARY
 Discussed the general characteristic of the virus family
 Emphasized some of the important viruses and their clinical impact to
man
 With learning the mode of transmission, we learned the salient feaures
of these viruses
 Learned how these viruses and its disease be prevented, controlled
and/or treated.

REFERENCES
th
 Jawetz, Melnick & Adelberg’s Medical Microbiology, 25 edition
th
 Madell’s Principles and Practice of Infectious Diseases, 7 edition
 www.cdc.gov
 www.doh.gov.ph/NEC/hiv-aids

edited by: Venus

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 Microbiology 3.10 DR. SENGSON
RNA Viruses II SEPT 25, 2013

Appendix A

RNA VIRUSES DOUBLE

STRANDED

SINGLE NON-
POSITIVE SENSE SEGMENTED
STRANDED SEGMENTED

NON NON
NEGATIVE SENSE SEGMENTED ENVELOPED
SEGMENTED ENVELOPED

NON- NON
SEGMENTED ENVELOPED REOVIRIDAE
SEGMENTED ENVELOPED

NON NON PICORNAVIRIDA

ENVELOPED ENVELOPED CORONAVIRIDAE
ENVELOPED ENVELOPED E

PARAMYXOVIRI ORTHOMYXOVIR
CALICIVIRIDAE TOGAVIRIDAE
DAE IDAE

RHABDOVIRIDAE
ARENAVIRIDAE HERPEVIRIDAE FLAVIVIRIDAE
BORNAVIRIDAE

FILOVIRIDAE BUNYAVIRIDAE ASTROVIRIDAE RETROVIRIDAE

HEPATITIS C

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 MICROBIOLOGY 3.10

Appendix B

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