Download Lec 4 Virology *Double strand DNA viruses Genome organization

Lec 4
Virology
*Double strand DNA viruses
Genome organization within this group varies considerably. Some have circular
genomes,( Papovaviridae) while others have linear genomes (Adenoviridae,
Herpesviridae and some phages). Some families have circularly permuted linear
genomes (phage T4 Others have linear genomes with covalently closed ends
(Poxviridae )
*Herpesviridae :
*Introduction :
Eight human herpesvirus species are known. All have the ability to
enter a latent state following primary infection of their natural host and
be reactivated at a later time.
*Structure of herpesviruses
Herpesvirus virions consist of an icosahedral capsid enclosed in an
envelope derived from the host’s nuclear membrane (see figure 25.2.page 256from
Microbiology -book 2013)
Between the envelope and the capsid lies an amorphous proteinaceous
material called tegument, which contains virus-encoded
enzymes and transcription factors essential for initiation of the infectious
cycle, although none of these is a polymerase. The genome is
a single molecule of linear, double-stranded DNA, encoding from 70
to 200 proteins, depending on the species.
Replication of dsDNA viruses :
In order to replicate any virus must be
1- produce mRNA
2- produce new virus progeny
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All DNA viruses replicate in nucleus except Poxviruses replicate in cytoplasm .
: Mechanisms of dsDNA virus genome replication include steps are
1-Early transcription of mRNA from viral DNA by host RNA polymerase .(in
nucleus)
2-Early translation for mRNA on ribosomes ( in cytoplasm) into non structural
proteins ( necessary enzymes) including synthesis of a single, long polyprotein, which
is processed by viral proteases including the viral DNA dependent DNA
polymerase needed to synthesize template for multiple copies of progeny negative strand DNA .
3-late transcription of mRNA from new DNA.(in nucleus )
)late translation for nonstructural proteins ( e.g : capsid protein45-Assembly new progeny DNA genome and capsid .
6-Realeasing by budding or fusion with cell membrane of infected cells
Replication of dsDNA viruses (see figure23.11,page 238from Microbiology -book
2013)
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*Classification of herpesviruses:
Herpesviridae cannot readily be differentiated by morphology in the
electron microscope, because they all have similar appearances.
However, Herpesviridae have been divided into three subfamilies,
based primarily on biologic characteristics :
1-Alphaherpesvirinae(herpes simplex virus group): These viruses
have a relatively rapid, cytocidal or lytic growth cycle and establish
dormant or latent infections in nerve ganglia. Herpes simplex
virus types 1 and 2 (HSV-1 and HSV-2) and varicella-zoster virus
(VZV) belong to this group.
2-Betaherpesvirinae (cytomegalovirus group): These viruses have
a relatively slow replication cycle that results in the formation of
characteristic, multinucleated, giant host cells. Latency is established
in nonneural tissues, primarily lymphoreticular cells and
glandular tissues. Human cytomegalovirus (HCMV) and human
herpesviruses types 6 and 7 (HHV-6 and HHV-7) are in this
group.
3-Gammaherpesvirinae (lymphoproliferative group): These viruses
replicate in mucosal epithelium and establish latent infections primarilyin B cells.
They induce cell proliferation in and immortalize
lymphoblastoid cells. Epstein-Barr virus (EBV) and human herpesvirus
type 8 (HHV-8) represent this group .
Note (2): Replication of Herpesviridae similar to replication of other dsDNA (
see figure 25.3p257/Microbiology -book 2013) .
*Human cytomegalovirus :
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Introduction :HCMV is a member of the Betaherpesvirinae subfamily and, as
suchdiffers from HSV and VZV in several ways. Its replication cycle is
significantlylonger, and infected cells typically are greatly enlarged and
multinucleatedhence, “cytomegalo-”) as shown (Figure25.14 p26 Microbiology book 2013) There isonly one recognized human species of HCMV.
Figure :Cytomegalovirus infection in Lung : section showing typical owl-eye
(see figure 25.14 page 254 from Microbiology -book 2013)
*Epidemiology :
Initial infection with HCMV commonly occurs during childhood . Depending on
geographic location and socioeconomic group, 35 to
09percent of the population have antibody against the virus by
adulthood.
*Transmission :Infection in children is usually asymptomatic, and
these children continue to shed virus for months in virtually all
body fluids, including tears, urine, and saliva . transmission is by :
1- contact with above fluids .
2- sexual sexual means because it is present in semen and vaginal
Secretions .
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3- organ transplants .
4-blood transfusions :Similarly, virus is present in breast milk, and neonates can
beinfected by this route.
5-HCMV can also cross the placenta andinfect a fetus in uterus .
*Clinical signs and Pathogenesis :
1- Initial replication of the virus in epithelialcells of the respiratory (lungs)and
gastrointestinal (GI) tracts is followedby viremia and infection of all organs of the
body.
2- In symptomaticcases, kidney tubule epithelium, liver, and CNS, in addition to
therespiratory and GI tracts, are most commonly affected.
3-Latency is probably establishedin monocytes and macrophages.
4-Persistent fever, muscle pain, and lymphadenopathyare characteristic are elevated
level of abnormal lymphocytes and liver enzymes .
5-Congenital infections: Results ofthe infections withHCMV damage of
liver,spleen, blood-forming organs, and components of the nervous systemlead to
fetal death. Damage to the nervous system is a commoncause of hearing loss and
mental retardation.
6-coinfection with HCMV may accelerate theprogression of the pathology of AIDS .
*Laboratory Identification ( Diagnosis ):
1- Serologic diagnosis by rapid test depend on antigen –antibody reaction .
2-Serologic diagnosis usingELISA (or, enzyme-linked immunosorbent assay)
techniques can distinguishprimary from recurrent infection by demonstrating IgG
seroconversion or the presence of HCMV-specific IgM.
3-Direct determination of the presence and amount of viral DNA or proteins
inwhite blood cells is useful as an indicator of invasive disease.
*Single strand DNA viruses
*Parvovirus ( ssDNA):
Parvovirus B19 infects only humans . Human parvovirus B19 is a 20-25 nm nonenveloped single-strand DNA virus which belongs to the family of parvovirus. B19V
has high tropism to bone marrow cells, particularly to the erythroid progenitors. The
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infection of B19 virus in susceptive individuals may cause a variety of serious
illnesses. B19V is generally transmitted via respiratory route or vertically from
mother to infant. However, B19V is frequently transmitted through blood or plasma
products.
.
*Symptoms
Parvovirus B19 most commonly causes fifth disease, a mild rash illness that usually
affects children. You can have a range of symptoms depending on your age and
overall health. About 2 out of 10 people who get infected with this virus will not have
any symptoms. Others may have only mild, cold-like illness.
Other much less common symptoms of parvovirus B19 infection include painful or
swollen joints which is more common in adults, and severe anemia. In rare cases,
some of these symptoms can persist for a long time.
*Transmission
Parvovirus B19 spreads through respiratory secretions (such as saliva, sputum, or
nasal mucus) when an infected person coughs or sneezes. Parvovirus B19 can also
spread through blood or blood products. A pregnant woman who is infected with
parvovirus B19 can pass the virus to her baby.
Note (1) : Replication of ssDNA same as dsDNA except the first step in
replication ssDNA convert to dsDNA by host DNA polymerase .
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