Parvoviruses are the smallest known human viruses. They require actively dividing host cells to replicate and can cause a range of diseases. Human Parvovirus B19 commonly causes Fifth disease in children, characterized by a rash on the cheeks and limbs. It can also result in transient aplastic crisis in patients with chronic hemolytic anemias, as well as hydrops fetalis if acquired vertically during pregnancy. Laboratory diagnosis involves cell culture, serology to detect antibodies, and molecular detection methods like PCR to detect the virus.

1. 2/19/2016 Dr. Kaveh Haratian, Dept. of Microbiology and Immunology, ABZUMS 1
An Introduction to
Parvoviridae

2. The most dependent viruses
• Latin Parvus = small
• The smallest of all human viruses(only 20-25 nm in diameter).
• It might be thought that viruses as a class represent the ultimate in
parasitism.
• Reliant as they are on their host cells to provide most of the machinery or
replication.
• The Parvoviruses, show a still further degree of dependence .
• As they can replicate only in the presence of active DNA synthesis in
rapidly dividing host cells, or under the influence of another virus
infection(helper virus).
• The reason lies in their minute size(smallest of all human viruses).
2/19/2016
Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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3. Little about it`s small genome
• Contain so little genetic information.
• Consist of a single icosahedral shell, surrounding a linear single-
stranded DNA molecule of very limited coding potential:
• 5kb for human parvovirus B19
• 4.7kb for human dependoviruses
2/19/2016
Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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4. More about it`s small genome
• The ssDNA genome is of negative polarity!
• But some virions package a positive strand instead(up to 50% of
them in the case of the genus Dependovirus).
• All genomes display long terminal palindromic sequences enabling
each of ends of the molecule to fold back on itself to form a hairpin
structure.
2/19/2016
Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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5. Major fact about their replication
• They are able to replicate only in dividing cells,
• Or, In the case of members of the Dependovirus genus, in the
presence of a helper virus.
• This requirement for dividing cells accounts for their predilection
for:
• Bone marrow
• Gut
• Developing fetus
2/19/2016
Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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6. • Parvoviruses of cats, dogs, and mink cause panleukopenia and
enteritis.
• Rat parvovirus causes congenital malformation of the fetus.
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Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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7. Human parvovirus B19
• Discovered in the serum of asymptomatic blood donors.
• Associated with:
• A very common exanthematous disease of children (Fifth disease)
• Aplastic crisis (in patients with chronic hemolytic anemia)
• Hydrops fetalis
2/19/2016
Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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5th.

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Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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9. More infections
Another human
parvovirus cause
gastroenteritis
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Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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10. The capsid
• Composed:
• One major polypeptide
• Two minor polypeptides
• Arranged to form 60 protein subunits.
2/19/2016
Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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11. Some physicochemical properties
• The virus is very stable, resisting:
• 60˚C for some hours.
• Variation from pH 3 to 9
2/19/2016
Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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12. Simple Classification
Parvoviridae
Parvovirinae
Parvovirus Erythrovirus
H.Parvovirus
B19
Dependovirus Bocavirus Amdovirus
Densovirinae
Include 4
genera
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Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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13. Parvovirus replication
• Unlike the double-stranded DNA viruses !!
• ssDNA parviruses can replicate only in dividing cells.
• Parvoviruses replicate in the nucleus:
• Transcription and replication of the genome
• Accumulation of nonstructural proteins
• Assembly of virions
2/19/2016
Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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15. Parvovirus receptor & Co-receptors
2/19/2016
Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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16. Parvovirus replication
• No enzyme in the virion.
2/19/2016
Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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Viral
ssDNA
dsDNA
mRNA
Several
different
mRNA
Several
different
proteins
Cellular DNA polymerase
Cellular DdRp II
Alternative splicing
Nonstructural and structural proteins are
encoded by the left and right side of the genome
respectively
Transactivation vs. down regulation

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Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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Genome replication
Palindromic 3` terminal sequence
Ds-replicative
intermediateform
In infected bone marrow cells
(concatemers)

18. Parvovirus:Clinical aspect
• Parvovirus clinical syndromes:
• Erythema infectiosum(fifth disease)
• Arthritis (especially in young women)
• Aplastic crisis in chronic hemolytic anemia
• Chronic anemia in immunodeficiency syndromes
• Hydrops fetalis
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Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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19. Clinical aspects
Intranasal
inoculation
Viremia
• Short lived
• High level
Shedding from
throat
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Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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Over a week
few
days

20. Clinical aspects
• Patients displayed a biphasic illness:
• (day 8-11) Fever, malaise, myalgia, chills, peak level of virus in blood,
destruction of erythroblasts in bone marrow.
• (day 17-24) rash and arthralgia occurred, viremia had disappeared, IgM had
peaked, IgG had begun to rise.
2/19/2016
Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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21. Erythema infectiosum
• Fifth disease
• Innocuous contagious exanthema of childhood.
• Erythematous rubella-like rash on face flushed cheeks
• Though fleeting: rash may reappear in weeks /months.
• Arthralgia:
• Children: occasionally
• Adult: regular
• Especially in women: peripheral joints: hands, wrists, knees, ankles.
• Polyarthritis is often the dominant feature
• 20-25% of infections are asymptomatic.
2/19/2016
Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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Limbs
Trunk
Fades rapidly in 1-2 day,
a fine lace

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Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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The pathogenesis of erythema infectiosum is probably a
result of antibody-antigen immune complex depositions
in skin, blood vessels and synovia. The rash typically
appears on the cheeks followed by a lace-like
maculopapular rash on the upper part of the body. Joint
symptoms are more common in adults than in children.
In addition to deposition of immune complexes, the
inflammatory response in synovial tissue may be a result
of the secreted phospholipase A2 motif in the unique
region of the B19 minor capsid protein .

23. Transient Aplastic Crisis(anemia)
• Temporary, potentially life-threatening complication in:
• Chronic hemolytic anemia:
• Sickle cell anemia
• Thalassemia
• Hereditary spherocytosis
• Characteristics of severe anemia:
• Pallor, weakness, lethargy
• Recovery occurs spontaneously in a week.
• Blood transfusion is sometimes lifesaving.
2/19/2016
Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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Infected with
Parvovirus B19
Usually norash
Sudden drop in hemoglobin
Total disappearance of
erythrocytes precursors
from bone marrow
Reticulocytes from the
blood

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Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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B19 binds to immature erythroblasts thereby arresting
production of mature erythropoietic cells. Following acute
infection, the reticulocyte count in peripheral blood is zero and
if the patients have an underlying disorder with pathologic red
cell survival, the number of erythrocytes may fall dramatically
in peripheral blood. The pathogenesis of thrombocytopenia is
thought to be explained by the cytotoxicity
of the NS1 protein .

25. Parvovirus B19: other complications
• Chronic anemia in immunodeficient patients in:
• Acute leukemia on chemotherapy
• AIDS patients
• Bone marrow recipient transplant
• Children with congenital immune deficiency state.
• Hydrops fetalis: general edema :
• Severe anemia
• Congestive cardiac failure
2/19/2016
Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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Dying of fetuses

26. Parvovirus in pregnancy
2/19/2016
Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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Vertical transmission of B19 from a primary infected mother
may cause fetal infection. Pathogenic mechanisms include
development of acute anemia upon infection of fetal
hematopoietic cells. In early pregnancy hematopoiesis is seen
in the liver and in later pregnancy this shifts to the bone
marrow. The anemia may resolve spontaneously or proceed by
causing cardiac failure and development of hydrops fetalis and
in rare cases fetal death. The virus may also cause myocarditis
and heart arrest by direct infection of myocardial
tissue. Modified from Anderson and Young .

27. Clinical complications associated with B19
2/19/2016
Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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28. Epidemiology
• Ubiquitous, common, highly contagious.
• Year-round infection, spring epidemics among school-children 4-10 years.
• Readily transmitted by:
• Respiratory secretions & close contacts
• During the incubation period of erythema infectiosum
• Chron.hemo. Anem. Patients are infectious up to 1 week after aplastic crisis.
• B19 in immunocompromised patients: excrete virus for months/years.
• Transplacental transmission:
• Less than 10% leads to fetal death.
• Rarely congenital malformations
• Blood transfusion:
• Factor VIII is a great problem
2/19/2016
Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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Attack rate:25 – 50%
Rash appearance: no
more infectious
30% maternal infections
transmit into fetus
Usually no harm!
The virus is heat stable:
survive in clotting factor
concentrate

29. Treatment and control
• Erythema infectiosum requires no treatment.
• Aplastic crisis requires supportive care and blood transfusion.
• Severe persistent anemia(Immunocomp. Patients) requires IVIG.
• Persons of potential risk:
• Pregnant non-immune women
• Immunocompromised individuals
• Chronic hemolytic anemia
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Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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30. B19 in different risk groups
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Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
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31. Dependoviruses
Adeno-associated viruses
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ABZUMS
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ABZUMS
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33. Laboratory diagnosis
• Cell culture :
• bone marrow, fetal lever (with erythropoietin & IL-3).
• MB-02(H.megakaryocytic leukemia cell line)(with GM-CSF).
• Serology :
• EIA/RIA: IgM or significant rise of IgG.
• Molecular detection:
• Detection of virus DNA by:
• Nucleic acid hybridization
• PCR
• EIA: for viral antigens
• EIA
• Electron microscopy:
• Nuclear inclusion bodies: crystalline array of virions in nucleus.
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Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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Antigen produced by molecular
cloning
In hydrops fetalis:
in situ hybridization

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Dr. Kaveh Haratian, Dept. of Microbiology and Immunology,
ABZUMS
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