Unit 4: Virology
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Lecture 13 - DNA Non-enveloped Virus
I- Adenoviruses
They are non-enveloped with icosahedral symmetry, DS-
DNA. They are the only viruses with a fiber protruding
from each of the 12 vertices of the capsid. The fiber is the
organ of attachment and is a haemagglutinin. The free
fibers are toxic to man.
There are 41 known antigenic types. The fiber protein is
the main type specific antigen. Group specific antigen
located on the hexon protein.
Certain serotypes cause sarcoma at the site of injection in
laboratory rodents such as newborn hamsters. There is no
evidence that adenoviruses cause tumors in human.
Replicative cycle
1) After attachment to the cell surface via its fiber, the virus
penetrates and uncoats, and the viral DNA moves to the
nucleus.
2) Host cell DNA-dependant RNA polymerase transcribes
the early gene resulting in mRNA.
3) Early mRNA is translated into nonstructural proteins in
the cytoplasm.
4) After viral DNA replication in the nucleus, late mRNA is
transcribed and then translated into structural virion
proteins.
5) Viral assembly occurs in the nucleus, and the virus is
released by lysis of the cell, not by budding.
Transmission
1) aerosol droplet
2) fecooral route in young children
3) direct inoculation of conjuctivas by tonometers or fingers
Epidemiology
Serotypes 3,4,7,21 cause respiratory disease.
Types 8 and 19 cause epidemic conjunctivitis
Types 11,21 cause hemorrhagic cystitis.
Type 40, 41 cause infantile gastroenteritis.
Pathogenesis
Adenovirus infects upper and lower respiratory tracts,
gastrointestinal tract, and conjunctivas.
Adenoviruses may become latent in adenoidal and
tonsillar tissues of the throat.
Clinical findings
Upper respiratory tract: pharyngitis, pharyngo-
conjuctival fever, and acute respiratory disease
characterized by fever, sore throat & coryza &
conjunctivitis
Lower respiratory tract: bronchitis & atypical pneumonia
GIT: Non bloody diarrhea
Haematuria and dysuria in hemorrhagic cystitis.
Laboratory diagnosis
Isolation by culture and fourfold increase in antibody titer
Treatment
No antiviral therapy.
Prevention
Three live non attenuated vaccines against serotype 4, 7,
and 21. each f the three vaccine are monovalent. And they
are given separately for each serotype to prevent
interference if given together. The vaccine is delivered by
an enteric coated capsule, which protects the live virus
from inactivation by stomach acid. The virus infects the
GIT, where it causes an asymptomatic infection and
induces immunity to respiratory disease. It is available for
only military.
II- Papilloma virus
Human papilloma virus causes papilloma which is a
benign tumor of squamous cells. Some HPV types
especially type 16,18 cause carcinoma of the cervix, penis
and anus.
Properties
HPV are non-enveloped viruses with DS circular DNA
and an icosahedral nucleocapsid. Two of the early genes
(E6,E7) are implicated in carcinogenesis. They encodes
proteins that inactivate proteins encoded by tumor
suppressor genes in human calls (e.g., p53 and the
retinoblastoma (RB) genes). Inactivation of these two
proteins are important step in the process by which a
normal cell become a cancer cell.
There are at least 100 types of papilloma viruses. Type 1-
4 cause skin warts, type 6and 11 cause genital warts
(condylomata acuminata) .
About 30 types infect the genital tract.
Replicative cycle.
1) the virus cant grown in cell culture
2) in human tissue, infectious viral particles are found in the
terminally differentiated squamous cells rather than in the
basal cells.
Unit 4: Virology
211
3) The HPV initially infects the cells of the basal layer in the
skin, but no virus is produced by those cells. Rather,
infectious virions are produced by squamous cells on the
surface which enhances the likelihood that efficient
transmission will occur.
4) In malignant cells, viral DNA is integrated into the host
cell DNA in the vicinity of cellular proto-oncogenes,& E6
and E7 are over- expressed. But in latently infected non-
malignant cells, the viral DNA is episomal and E6 and E7
are not over-expressed. This differences occurs because
another early gene,E2, control E6 and E7 over-expression.
The E2 gene is functional when the viral DNA is
episomal but it is inactivated when it is integrated.
Transmission and epidemiology
HPV are transmitted by skin to skin contact. Genital warts
are among the most common sexually transmitted disease.
Skin warts are more common among children and young
adults. They tend to regress in older adults.
HPV transmitted from an infected mother to neonate
during child birth causes warts in the mouth and the
respiratory tract especially the larynx of the infant.
The virus infect squamous epithelial cells and induce
characteristic cytoplasmic vacuoles, these cells called
Koilocytes.
Laboratory diagnosis
Infections are usually diagnosed clinically.
A PCR based test using Cobas 4800 system is approved to
detect the presence of DNA of 14 high risk genotypes,
including type 16 and 18.
Diagnostic test based on detection of antibodies in a
patients serum or on isolation of the virus from a patients
tissue are not used.
Treatment and prevention
The usual treatment of genital warts is Podophyllin
Liquid nitrogen is used in the treatment of skin warts
Plantar warts is treated surgically with topical salicylic acid
Cidofovir is used in the treatment of severe HPV infection.
There are two vaccines against HPV
Gardasil contains capsid protein of 6,11, 16,18.
Cervarix is a recombinant vaccine and contain the
protein of types 16 and 18 only.
The role of cesarean section in preventing the transmission
of HPV from the mother to the baby is uncertain
Circumcision reduces the risk of infection by HPV.
III- Parvoviruses
Parvovirus B19 is a SSDNA none enveloped negative
sense with icosahedral symmetry virus. The virus has no
virion polymerase.
There is one serotype only.
It is transmitted by respiratory droplets, transplacental.
Blood transfusion can transmit the virus.
Clinical features.
1) Erythema infectiosum (slapped cheek syndrome, fifth
diseae.)
2) Aplastic anemia especially in patient with sickle cell
anemia, thalassemia and spherocytosis.
3) Fetal infection. If the infection is acquired during the first
trimester (fetal death) or in the second trimester (hydrops
fetalis). The virus is not associated with any congenital
anomalies.
4) Arthritis
5) Chronic B19 infection especially in pt with immunodeficiency.
Laboratory diagnosis
Fifth disease and aplastic anemia is diagnosed by
detecting IgM antibodies. Fetal infection is diagnosed by
PCR analysis of amniotic fluid.
Treatment
No specific treatment of B19 infection
Pooled immunoglobulin may have a beneficial effect on
chronic B19 infection in patient with immunodeficiencies.
IV- Polyomaviruses
2 members of the polyomavirus family that infect human
1)
JC
(causes progressive multifocal
leukoencephalopathy (PMLE)) BK (nephropathy in
renal transplant patients ) viruses.
2)
One member of SV 40
virus that is primarily a
monkey virus but has infected humans when it
contaminated the poliovirus vaccine..