PARVOVIRUSes

PALOMO
RICO
SALOMA
SILOMENIO
VICENTE
History
- due to their extremely small
size, parvoviruses were only
recently discovered

Dependoviruses
~ the first parvoviruses to be
discovered, were first isolated
in the 1960s
Parvovirus B19

he first known parvovirus to infect humans

~ was discovered in London by

Australian virologist Yvonne
Cossart in 1974.
-- focused on hepatitis B and were
processing blood samples when they
discovered a number of "false
positives" later identified as
parvovirus B19.
PROPERTIES
OF THE
VIRUS
Classification
ETYMOLOGY:
parvus Latin: small virus English
Family: Parvoviridae
Sub-family:Parvovirinae
Densovirinae
Densoviridiae Parvovirinae
Iteravirus Parvovirus
Contravirus Erythrovirus
Dependovirus
Bocavirus
Types

1. B19 &
Adenoassociated Virus
2. Canine Parvovirus
Type 2
3. Feline Panleukopenia
4. Porcine Virus
5. Kilham Rat Virus
Morpho-anatomy
CAPSID: Icosahedral symmetry
made with 2-4 VP1-proteins.
Naked viruses with a shape thats
roughly spherical, with surface
protrusions and canyons.
Genome
-ssDNA of about 4-6kb
-Each end: short complementary
sequences that can base pair to form a
secondary structure

Inverted Terminal Repeats (ITRs) Unique sequences

Non-structural protein: 3 end Structural proteins:

5 end
Replication
ATTACHMENT &
ENTRY
1. Attaches to host
receptors, enters
through endocytosis
2. Released from
endosome into the
cytoplasm,
transported to the
nuclear pore using
microtubules
 TRANSCRIPTION & TRANSLATION
3. RNA polymerase transcribe the virus genes
4. The primary transcripts undergoes splicing event,
producing 2 size mRNA classes of mRNA
- larger: non-structural proteins
- smaller: structural proteins
- Non-structural proteins: phosphorylated,
involved with gene expression and NDA
replication
 DNA REPLICATION
6. ROLLING-HAIRPIN REPLICATION
a leading strand mechanism replicating their
genomes through leading & lagging strand
synthesis
7. Procapsids are constructed from structural
proteins, each filled by a copy of the virus genome
either (+)/(-) DNA.
8. One of the non-structural proteins functions as a
Epidemiology
B19
virus
Present throughout the year in temperate
climate outbreaks; more common in
spring and summer
Most common: 4 10 year olds;
outbreaks in nurseries and schools
Respiratory transmission through
droplets; blood borne is rare
No vaccine yet
Clinical &
Pathological
aspects
Clinical Features
Characteristic Features
Pathogenesis & Pathology
 REPLICATION AS DISEASE
VECTOR
To enter host cells, parvoviruses bind to a sialic
acid-bearing cell surface receptor.
Penetration into the cytoplasm is mediated by a
phospholipase A2 activity carried on the amino-
terminal peptide of the capsid VP1 polypeptide.
Once in the cytoplasm, the intact virus is translocated
to the nucleus prior to uncoating.
Transcription only initiates when the host cell
enters S-phase under its own cell cycle control, at
which time the cell's replication machinery converts
the incoming single strand into a duplex transcription
template, allowing synthesis of mRNAs encoding the
non-structural proteins, NS1 and NS2.
The mRNAs are transported out of the nucleus into
 Viral DNA replication proceeds through
a series of monomeric and concatemeric
duplex intermediates by a unidirectional
strand-displacement mechanism that is
mediated by components of the host
replication fork, aided and orchestrated by
the viral NS1 polypeptide.
NS1 also transactivates an internal
transcriptional promoter that directs
synthesis of the structural VP
polypeptides.
Once assembled capsids are available,
replication shifts from synthesizing duplex
DNA to displacement of progeny single
strands, which are typically negative-
sense and are packaged in a 3'-to-5'
direction into preformed particles within
the nucleus.
Immune Response
Immunology of B19 Infection
1. Antibody response
In response to B19 infection, the immune system
responds by producing IgM and IgG antibodies. IgM
antibodies are detected at approximately 10 to 12
days after infection, whereas IgG antibodies can be
found 2 weeks after the infection and persist for life.
Initially, the early antibodies are produced against
VP2, the main viral capsid protein. As the B19
infection continues, antibodies react primarily to the
VP1 minor capsid protein (Fields 2368).

2. Role of antibodies
Interestingly, antibodies may serve two roles in B19
infections. While neutralizing antibodies help patients
clear the virus in both acute and persist infections,
Laboratory Diagnosis

FETAL
SPLEEN
Treatment
&
Control
Parvovi
DEFECTIVE
ruses
IMMUNITY
Introduction (Types of immune defect)

Immunodeficiency disorders prevent your

body from fighting infections and diseases.
This type of disorder makes it easier for you to
catch viruses and bacterial infections.

Congenital, or primary
Acquired, or secondary
Primary Immunodeficiencies

occurs in the case when the problems or abnormalities of

the immune system develop from an inborn defect in the
cells.

Defects in antibodies, cells and proteins of the immune

system (for example,T cells,B cells, neutrophils, or the
complement system)

inability to make a very important type of protein called

antibodies or immunoglobulins, which help the body
fight off infections from bacteria or viruses. In addition to
increased susceptibility to infection, people with PI may also
have autoimmune diseases in which the immune system
attacks their own cells or tissues.
Classified by which part of theimmune
systemis affected:

Humoral immunity, which involvesB cells(lymphocytes), a

type of white blood cell that produces antibodies
(immunoglobulins)
Cellular immunity, which involvesT cells(lymphocytes), a
type of white blood cell that helps identify and destroy
foreign or abnormal cells
Both humoral and cellular immunity (B cells and T cells)
Phagocytes (cells that ingest and kill microorganisms)
Complement proteins(proteins with various immune
functions, such as killing bacteria and other foreign cells
and making foreign cells easier for other immune cells to
identify and ingest)
 Primary Immunodeficiencies
Predominantly affecting B cells and
antibody production
Antibody deficiency syndromes: this is a group of conditions
characterised by an inability to produce antibodies in sufficient quantity
or of sufficient quality.
Common variable immunodeficiency: this is a heterogeneous syndrome
characterised by various degrees of hypogammaglobulinaemia,
commonly associated with autoimmunity.
Thymoma and hypogammaglobulinaemia: this is characterised by low
numbers of B cells and a distinctive T-cell type.
X-linked (Bruton's agammoglobulinaemia): the agammaglobulinaemia
is an X-linked immunodeficiency in which there is a failure to produce
mature B-lymphocyte cells. The defect in this disorder is a fault in the
enzyme in Bruton's tyrosine kinase, a key regulator in B-cell
development.Novel genetic defects have been found.
Selective IgAD occurs in about 1/400 people.There is a selective
severe deficiency or total absence of IgA in serum and body secretions.
 Primary Immunodeficiencies
Predominantly affecting T cells and cell-
mediated immunity

Thymic aplasia (DiGeorge syndrome): there are genetic

defects of the thymus and often the parathyroid glands and
heart, associated with T-cell dysfunction and significant
immune deficiency.
Severe combined immunodeficiency disease: this is in fact a
group of rare congenital diseases in which there is severe
and usually fatal immune deficiency. It has gained the
attention of the media in the past and has been known as
'bubble boy disease'.
Inherited syndromes associated with immunodeficiency: a
wide range of inherited immunodeficiency conditions has
been identified, many involving a single gene.
 Virus infections associated with
primary immunodeficiencies

The host immune response to viruses is complex,

and some viruses predominantly elicit either a
cellular or humoral immune response. Even when
neutralizing antibodies or a specific cellular
response can be demonstrated in vitro, the
protective role of the humoral or cellular arms of
the immune system is often inferred from clinical
studies of susceptibility in immunosuppressed
patients or the results of vaccination. The
effectiveness of passive immunization with
immunoglobulin (hepatitis A, cytomegalovirus) or
hyper immune serum (hepatitis B, varicella)
 Infection in normal individuals is manifest as fifth
disease, in which the formation of complexes of
antibody and virus is associated with a cutaneous
eruption and polyarthralgia. In normal individuals
infected, either naturally or experimentally, with B19
parvovirus antibodies to virus form rapidly, usually
within a week of inoculation.
Fifth disease is itself an antibody-mediated, probably
immune complex disorder, occurring at the time that
antibodies are present in the circulation and seldom
associated with the presence of virus in serum.
Formation of neutralizing antibodies is a consistent
feature of acute infection in animals by members of
Parvoviridae
 Acquired immunodeficiencies
secondary to other disease and
their treatment
People who have a family history of primary
immunodeficiency disorders have a higher-than-normal
risk for developing primary disorders. Anything that
weakens your immune system can lead to a secondary
immunodeficiency disorder.
Persistent infection with B 19 parvovirus in humans
causes chronic anemia. Persistence has been
observed in the fetus (30) and in three populations of
immunosuppressed patients: congenital
immunodeficiency, acute lymphocytic leukemia
receiving chemotherapy, and AIDS.
 Formation of neutralizing antibodies is believed to have
a major role in resolution of acute infection in adult
animals (37), but virus-specific antibodie are often
present in persistently infected neonatal animals, and
abnormally elevated titers of antibody have been
associated with latency. Reappearance of clinical illness
in animals has followed immunosuppressive therapy. In
Aleutian mink disease, which is chronic and often fatal,
tissue damage is the result of deposition of immune
complexes of parvovirus antigen and antiviral IgG
antibodies that fail to neutralize virus.
 The treatment for each immunodeficiency disorder will
depend on the specific conditions. For example, AIDS
causes several different infections. Your doctor will
prescribe medications for each infection. And you may
be given an antiretroviral to treat and HIV infection if
appropriate.
Treatment for immunodeficiency disorders commonly
includes antibiotics and immunoglobulin therapy.
Other antiviral drugs, amantadine and acyclovir, or a
drug called interferon are used for treatment of the
viral infections caused by immunodeficiency
disorders.
If your bone marrow isnt producing enough
lymphocytes, your doctor might order a bone marrow
(stem cell) transplant.