ADENOVIRUS – Mastadenovirus – Mammalian
Aviadenovirus – Avians
 47 serotypes in 6 genera A,B,C,D,E & F –
cause human disease.
 Eg.-
a. upper and lower respiratory diseases like pharyngitis,
conjunctivitis, pneumonia, kerato-conjunctivitis can also
occur.
b. Gastroenteritis.
c. Hemorrhagic cystitis
d. In rodents it can cause sarcoma.
Properties - Non enveloped, ds-linear DNA,
Icosahedral nucleocapsid.
 Special feature – only virus with fiber - Protruding from each
of 12 vertices of the capsid. Fiber is organ of attachment, it is a
hemaggluttinin - also the main type of specific antigen.
 Group specific antigen is also located on the hexon protein.
 Serotypes 12,18,31 cause sarcomas at site of injection into lab
rodents. Eg. Newborn hamsters. No evidence in humans.
Replication –
 Fiber attach to cell surface.
 Penetration
 Uncoating – viral DNA to Nucleus
 Host cell DNA dependent RNA polymerase
transcribes early genes.
 Splicing enzymes remove the RNA representing
the introns- Leads to formation of RNA[Introns
and exons common in eukaryotic cell were first
described for adenovirus DNA]
 Early RNA is translated into non-structural proteins
in cytoplasm
 Viral DNA then replicates in the nucleus.
 Late MRNA is transcribed and translated into
structural viral proteins.
 Virus assembly in nucleus
 Virus released from cell by cell lysis [not budding]
Transmission Aerosol droplets
 Fecal oral
 Direct inoculation of conjunctiva by
tonometers or fingers.
 Animal strains not pathogenic to humans.
 Endemic world wide.
 Outbreaks can occur in military recruits, hostels etc. Meaning
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close living conditon favours transmission.
Eg. Types 3,4,7 & 21 can cause respiratory disease.
8,9 – epidemic keratoconjunctivitis
11,21 – Hemorrhagic cystitis.
40,41 – infantile gastroenteritis.
37 – cervicitis, urethritis [sexual transmission]
Pathogenic and immunity The name adenovirus is given because it was first
isolated from adenoids in 1953
 Infect mucosal epithelium of several organs. Eg.
Respiratory tract, G.I. tract and conjunctiva.
 Neutralising antibody develops following infection but
is type specific and may be life long.
 It also causes death of cell in acute infection but has
latency in adenoids and tonsils.
Clinical featuresURT – Pharyngitis, pharyngoconjunctival fever, acute
respiratory disease.
Fever, sore throat, coryza and conjunctivitis.
 LRT – Bronchitis, atypical
pneumonie.
 Hemorrhagic cystitis –
hematuria and dysuria
 Children under 2 years – Gastro enteritis with non
bloody diarrhoea.
 Adenovirus infections usually resolve
spontaneously .
 Approx 50% infections are asymptomatic.
Laboratory diagnosis Isolation of virus in cell culture [different specimens]
HeLa cell line, Hep-2, KB
etc. to observe CPE.
 It is also a exciting model
for vector – so tried in
gene therapy.
Direct – Inclusion body – basophilic
Electron Microscopy
 Immunofluorescence – using polyclonal or
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monoclonal antibody
For Feces – LA test, ELISA
Looking for viral DNA by electrophoresis.
Most imp. Serologic test – CF and haemagglutination
inhibition.
4 fold or greater Antibody titer increase [using the
paired sera procedure].
Treatment- No antiviral therapy
Prevention –
 iatrogenic keratoconjunctivitis
 maintain asepsis
 hand washing.
 Vaccine – live non attenuated vaccine for types 4,7,21
given separately as enteric coated capsules for military
only.
 Since 1998 it is discontinued.
PARVO VIRUS-Parvo virinae – infects vertebrates
-Densovirinae – infect insects
Parvovirinae – 3 genera
1. Parvo virus – diarrhoea in humans.
Animal virus – Feline Pan leukopenia virus
Canine parvo virus
Cause serious veterinary disease
2. Erythrovirus – B19 – divide rapidly in dividing cells
autonomously.
3. Dependo virus – defective virus and they depend on a
helper virus usually a adenovirus for replication. They
are human adeno associated virus not known to
cause disease
Diseases – B19 [Parvo B19]
 Erythema infectiosum or
slapped cheek syndrome or fifth disease.
 Aplastic crises – especially in sickle cell anemia
 Fetal infection – hydrops foetalis
 Pure red cell aplasia – suppression of bone marrow by
virus.
 Miscellaneous – doubtful – fulminant hepatitis,
meningitis, encephalitis, vasculitis, myocarditis,
cardiac allograft rejection and glomerulopathies in
renal transplants.
Properties –
 very small 22nm
 Non enveloped
 ss DNA genome [-ve strand]
 No virion polymerase
 One serotype with icosahedral symmetric capsid.
Replication Adsorption to host cell receptor
 Virion penetrate and moves to nucleus
 Replication occurs
 ss Genomic RNA is synthesized by the cellular RNA
polymerase with DNA acting as intermediate.
 Progeny virions assembled in the nucleus.
 B19 replicates only when the cell is in the ‘S’ phase.
 This is the reason why the virus replicates in red cell
precursor and not in mature red cells.
Transmission Respiratory route, blood transfusion.
 World wide in distribution – half of population has
antibodies to it.
 Natural reservoir – humans.
 Animals are not source for human infection
Pathogenesis and immunity2 type of cells are infected.
a. Red cell precursors in bone marrow – results in
aplastic crisis.
b. Cells of the endothelium – Partly contributes to the
rash
and immune complexes – virus + IgM or IgG
contributes to rash and arthritis.
 Infection and recovery gives life long immunity against
re-infection.
Clinical features- 4 main presentations.
a. Erythema infectiosum - slapped cheek syndrome,
fifth disease.
-Mild, mainly childhood disease. Bright red rash that is
most prominent in the cheeks.
-With low grade fever, running nose [coryza] and sore
throat.
 A ‘Lacy’ less intense erythematous rash appears on
the body.
 Symptoms resolve in a week.
 Main complication – B19 arthritis. Mostly in adultswomen
b. Aplastic crisis – children with chronic anaemia,
sickle cell anemia, thalassemia and spherocytosis
have transient but severe aplastic anemia – aplastic
crisis, when they are infected with B19 virus.
 People with normal RBC are not affected though their
RBC precursors are infected.
c. Fetal infection – women infected during pregnancy
virus may cross placenta and infect foetus.
1st trimester – foetal death, <10% before 20th week due to
severe anemia.
2nd trimester – hydrops foetalis.
3rd trimester – No important clinical finding
 B-19 is not a
common cause of
fetal abnormalities
d. Chronic B19 infection - Immunodeficiencies
especially HIV, chemotherapy or transplant patients –
chronic anemia, Leukopenia, thrombocytopenia.
Laboratory diagnosisSamples – serum, blood cells, tissue samples and
respiratory secretions.
 Most sensitive tests detect viral DNA
Eg. -Dot blot hybridization of serum or tissue extracts.
-In situ hybridization of fixed tissue.
-PCR
Serological assays -based on recombinant parvovirus
antigens derived from bacterial or baculovirus
expression systems.
Used to measure antibodies.
 For fifth disease and aplastic crises.
 Detect IgM antibody to B19.
 Indicates recent infection.
 Present for 2-3 months in the circulation after
infection
B19 IgG persists for years but not found in
immunocompromised [eg. AIDS]
So viral DNA in blood by PCR in these cases.
Fetal infection –
 PCR of amniotic fluid detects virus.
 Virus difficult to grow so not commonly done.
 Diagnostic tests are available only in a few
laboratories.
Treatment and prevention No specific treatment
 Pooled Ig have a beneficial effect on B19 infection in
immunodeficient patient.
 Fifth disease and aplastic crises are treated
symptomatically.
 No vaccine or chemoprophylaxis.
PAPILLOMA VIRUS –
 Papova viridae - Papilloma virus
 Polyoma virus
Causes – Papillomas – Benign tumors of squamous
epithelial cells – eg. Wart on skin
HPV – 16 – implicated to cause Cancer cervix
Properties –
 Non enveloped
 ds circular DNA
 Icosahedral nucleocapsid
 Belong to papova virus group.
 Similar to polyoma virus and SV40 virus.
 But longer, larger genome and antigenically distinct.
 Two early genes E6 & E7 are
implicated in carcinogenesis.
 These genes encode proteins –
that inactivate proteins encoded by tumor suppressor
genes in human cells.
Eg. p53 gene proteins suppressed by E6
RB [retinoblastoma] gene by E7.
 This inactivation of P53 & RB gene is important step in
the process by which normal cell becomes a cancer
cell.
 DNA restriction fragmentation analysis – 100 types of
papilloma viruses.
 These viruses have a very pronounced predilection
for certain tissue.
eg. Skin warts caused by HPV – 1 to HPV 4.
Genital warts HPV 6, HPV 11.
Replication- Little is known because virus grows very
poorly in cell culture or not at all.
 In human tissues infectious virus particles is situated in
the terminally differentiated squamous cells rather than
the basal cells.
 In malignant cell viral DNA is integrated into host cell
DNA near the cellular oncogenes.
 E6 &E7 are over expressed.
 But in latently infected non-malignant cell –viral DNA
is episomal, E6 & E7 not over expressed because of an
early gene called E2. This E2 controls E6 & E7
expression.
 This E2 is functional only when the viral DNA is
episomal but is inactivated when it is integrated.
Transmission and epidemiology Mainly by skin to skin contact and by genital contact.
 Genital warts is one of the most common STD.
 Animal virus is not source of human infection.
Pathogenesis and immunity Infected squamous cell show characteristic
cytoplasmic vacuole – This process is called
Koilocytoses.
 So Koilocytes are hall mark of papilloma virus
infection.
 Most warts are benign- do not progress to malignancy.
 But HPV is implicated in carcinoma cervix. Protein
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encoded by viral genome E6 & E7 interfere with
growth inhibiting protein produced by P53 and RB
gene.
So contributes to the oncogenicity of the virus.
Both CMI and AMI involved.
Spontaneous regression of warts can take place
because of this.
More extensive warts in immunocompromised . Eg.
AIDS.
Clinical features Predominant finding is papillomas of various organs.
 Specific HPV types cause.
 Skin and plantar wart HPV 1, HPV 2, HPV 3 & HPV4.
 Genital wart – condyloma accuminata – HPV 6,
HPV 11.
 Carcinoma of cervix, the penis, anus.
 Premalignant lesion called intraepithelial neoplasia –
HPV-16, HPV 18.
 Occult premalignant lesion of cervix and penis can be
revealed if you apply acetic acid to tissue.
Laboratory diagnosis Clinically
 Histopathology – Koilocytes in lesion
 DNA hybridisation tests [commercially available] –
detects presents of viral DNA.
 Serology rarely done.
 Culture unsuccessful.
Treatment and prevention Genital warts – Podophyllin.
 Alpha interferon – effective and better for preventing
recurrences than antiviral treatment.
 Liquid nitrogen commonly used for skin warts.
 Plantar warts – surgical removal, topical salicylic acid.
 Vaccine is marketed nowadays (recombinant vaccine
containing antigen HPV6,11,16 & 18 for adolescent &
young women.
 Common counseling for sexual behavior.
Polyoma and SV40 Virus Best characterised oncogenic papova viruses of
animals
 Poly=many, ma=tumour
 Cause wide variety if histologically different tumor
when inoculated into newborn rodents
 Natural host is mouse
 SV40 isolated from normal Rhesus monkey kidney
cells
 Causes sarcoma in new born hamsters
 Polyoma and SV40 share many chemical and
biological features
- ds circular super coiled DNA of mol.wt. 3x10⁶
- 45 nm icosahedral nucleocapsid
 sequence of DNA and antigens are different
 Both undergo a lytic or permissive cycle in cells of their
natural host with production of progeny virus
 If they infect cells of heterologous species, non-
permissive cycle occurs, no virus is produced , cell is
malignantly transformed
 In transformed cells, viral DNA integrates into the cell
DNA and only early proteins are synthesized.
 Some of the proteins like T antigen are required for
induction and maintenance of transformed state
JC virus- (John Cunningham virus)
 Human papova virus
 Causes progressive multifocal leukoencephalopathy
 This is a fatal demyelinating disease of white matter
and multiple areas of brain involved
 This occurs primarily in compromised CMI especially
in AIDS
 Antigenically this virus is distinct from others like
HPV
 75% of normal people have antibodies to JC virus
meaning infection is widespread
 Disease occurs when latent virus is activated in an
immuno compromised
 Diagnosis- electron microscopy of diseased brain
tissue
-Cytology – exfoliated urine – enlarged cells with deeply
stained basophilic nuclei with a single inclusion
 Virus isolation- urine or brain biopsy material grown
in fetal glial cell culture
- Growth made out by the Haemagglutination
inhibition test
 Viral antigen – ELISA of urine sample,
immunofluorescence of biopsy material
 Viral nucleic acid – nucleic acid hybridisation and PCR
 Autopsy- in situ hybridisation of brain biopsy material
BK virus isolated from urine of renal transplant recipient
 Subclinical infection seen in children before 10 yrs of
age
 Upper respiratory symptoms
 Persists for life in kidneys
 Reactivation can occur during the last trimester of
pregnancy and also following immunosuppression for
organ transplants
 Leads to asymptomatic shedding in urine
 Diagnosis-
Electron microscope – urine of renal transplant
patient. Detection of viral antigen of ELISA
2. cytopathology- similar to JC virus
3. Virus isolation- human diploid fibroblasts
4. Detection of viral nucleic acid – PCR, DNA
hybridization
1.