Transcript Cardiovascular system infection:

Sexually Transmitted Viral Infections:
The most common viral causes are:
1.
Herpes simplex virus type 2 (HSV-2)
2.
Human papillomavirus (HPV)
3.
Human immunodeficiency virus (HIV)
4.
Human cytomegalovirus (HCMV)
5.
Hepatitis B virus (HBV)
6.
Molluscum contagiosum virus (MCV)
Prevalence of Common Viral Diseases:
Herpesviridae Family:

Icosahedral, enveloped double stranded DNA viruses.
Genome consists of long and short fragments which may
be orientated in either direction, giving a total of 4 isomers.


Three subfamilies:

Alphaherpesviruses: HSV-1, HSV-2, VZV

Betaherpesviruses: CMV, HHV-6, HHV-7

Gammaherpesviruses: EBV, HHV-8
Set up latent or persistent infection following primary
infection

Reactivation are more likely to take place during periods
of immunosuppression.

Herpes virus Particle
HSV-2 virus particle
Note that all herpesviruses
have identical morphology
and cannot be distinguished
from each other under
electron microscopy
 Herpes Simplex Virus Type 2 (HSV-2):
Double stranded DNA enveloped virus with a genome of
around 150 kb

The genome of HSV-1 and HSV-2 share 50-70%
homology.

They also share several cross-reactive epitopes with each
other.


Man is the only natural host for HSV.

Transmission of HSV-2 by:
A. Sexual contact, or
B. Infection during birth.
Pathogenesis:
Primary infections commonly asymptomatic;
Symptomatic cases sometimes severe, prolonged, systemic
manifestations:
- Fever
- Myalgia
- Local pain
- Itching
- Painful vesiculoulcerative lesions: on the vulva, cervix
and vagina or the penis.


Latency of HSV-2 is in sacral ganglia

Reactivation often asymptomatic.
o
Takes place during sexual intercourse.
o
Manifest at any site innervated by the affected neurons.
HSV-2 Diseases:
1) Herpes genitalis:
- The classical presentation.
- Extensive bilateral painful vesicular lesions in the
genital area, accompanied with fever, dysuria and
inguinal lymphadenopathy.
2) Neonatal herpes:
- The most serious consequence of genital herpes.
- it is acquired during birth.
3) Aseptic meningitis.
Genital Herpes Simplex in Males
Genital Herpes Simplex in Females
Laboratory Diagnosis:
Identification is very important to prevent neonatal
infection and HSV encephalitis.
1- Isolation of virus on tissue culture
2- Detection of HSV in vesicle fluid by electron
microscopy
3- Detection of viral DNA by PCR
4- Detection of viral antigen by direct immunofluroescence
or ELISA.
5- Serological diagnosis to detect IgM antibodies that
indicates recent infection or reactivation
Diagnosis of HSV-2:
Cytopathic Effect of HSV in cell culture:
Note the ballooning of cells.
Positive immunofluorescence test
for HSV antigen in epithelial cell.
 Human Cytomegalovirus (HCMV):


Belong to the betaherpesvirus subfamily of
herpesviruses
The name “cytomegalo-” account for the swollen state
of virus-infected cells. The infected cells are typically
enlarged and multinucleated.

Double stranded DNA enveloped virus

The structure of the genome of CMV is similar to
other herpesviruses, consisting of long and short
segments which may be orientated in either direction,
giving a total of 4 isomers.
Pathogenesis:
Transmission:
1.
2.
3.
4.
5.
Sexual intercourse.
Blood transfusion.
Organ transplantation.
Breast feeding.
Transplacental.
Primary infection: usually asymptomatic
In symptomatic cases, CMV replicates in epithelial cells of
respiratory and gastrointestinal tracts
viremia
infection of all organs of the body.
Latency: in monocytes and macrophages.
Reactivation: common in immunocompromised persons.
Clinical Features:
1) Congenital infection:
may result in “cytomegalic inclusion disease” leads to
congenital abnormalities as:
- Growth retardation.
- Microcephaly.
Hepatosplenomegaly
- Thrombocytopenia
Blindness
2) Postnatal infection: usually asymptomatic. However,
in a minority of cases, the syndrome of infectious
mononucleosis may develop which consists of fever,
lymphadenopathy, and splenomegaly.
3) Infections of immunocompromised patients: such as
transplant recipients and AIDS patients ;
Severe CMV disease such as pneumonitis, retinitis,
colitis, and encephalopathy.
Congenital Cytomegalovirus Disease:
Three-week-old infant with congenital cytomegalovirus infection with
purpuric skin lesions and hepatosplenomegaly
.
Laboratory Diagnosis:
1) Isolation of the virus from throat washings, urine, exudate
on tissue culture.
2) Detection of viral DNA by PCR.
3) Detection of viral antigens in urine or saliva.
4) Serodiagnosis: Detection of CMV specific IgM or rising
titre of IgG by ELISA or latex agglutination assay.
Lung section showing
typical owl-eye inclusions.
 Human Papillomavirus (HPV):
•
•
Family: Papovaviridae.
Non enveloped, icosahedral, epitheliotropic double
stranded supercoiled DNA virus.
•
It is estimated that 75% of the adult population will
have at least one HPV infection during their lifetime.
•
Has great tissue and cell specificity, infecting only
surface epithelia of skin and mucous membranes.
•
The genome is contained within a spherical protein
capsid with 7 early proteins (E1 to E7), and 2 late
structural proteins (L1 and L2).
•
•
•
Based on L1 gene sequence difference, there are over
100 types of HPV; 40 can cause anogenital infection.
Low-risk HPV types: cause anogenital warts and other
benign lesions
High-risk HPV types: are associated with malignant
carcinomas (mainly of the cervix).
Pathogenesis:
Transmission:
1.
2.
3.
Sexual contact.
Contaminated surfaces (fomites)
From mother to an infant during delivery (rare)
How Does HPV “Cause” Cancer?

HPV produces a chronic infection of basal cell layer of
stratified squamous epithelium.
 HPV DNA persist non integrated in normal infected
cells.
 But integrated in host cell chromosome in high grade
dysplasia cells
high expression of E6 and E7
genes
high expression of E6 and E7 proteins.
HPV Infection Outcomes
In high-risk HPV strains:
E6 and E7 interact with many cellular proteins, which
influence the outcome of infection.
• Protein E6 interacts with
p53 in the host cell and
promotes it’s degradation.
• Protein E7 complexes with
retinioblastoma protein (Rb),
thereby inactivating it.
• Rb and p53 are both tumor
suppressors, involved in
DNA repair and cell death.
p53
bax
p21
E6
interactions
E7
interactions
Apoptosis
Growth Arrest
Clinical Picture:
1) Genital warts:
- Skin growths in the anogenital area with cauliflower-like growths.
- In women, genital warts can appear on the vulva, urethra, cervix,
vagina, anus or thighs.
- In men, warts can appear on the penis, scrotum, anus or thighs.
-Genital and anal warts are very contagious (transmitted by personperson skin contact).
-Sometimes genital warts last for years and sometimes disappear
without treatment.
- Genital and anal warts can sometimes come back.
HPV Perianal Wart:
HPV Penile Warts:
2) Cancer of the genital tissues:
High risk types of the HPV virus are linked to cervical cancer as
well as cancers of the penis, of the anus and other genital cancers.
In women, pre-cancerous cells can be detected in the cervix by a
Pap test.
It is unlikely that a young girl will be diagnosed with cervical cancer
as it takes many years for a cancer to develop.
What is a Pap test ?
A Pap test is an examination of a woman’s internal genital organs.
It is the only way to detect abnormal cells in the cervix that could
potentially develop into cancer later in life.
A girl should have her first Pap test within 3 years of becoming
sexually active.
Laboratory Diagnosis:
1. HPV cannot be cultivated to diagnose infections.
2. For cervical screening:
Cervical swabs or biopsy samples are subjected to:
a. Cytology (Pap smear)
b. Detection of cervical biomarkers:
include E6 and E7
c. Hybridization or PCR molecular assays:
to detect HPV L1 DNA sequences, E6 or E7 mRNA