Adenoviruses are medium sized non-enveloped DNA viruses that commonly cause respiratory, eye, intestinal, and urinary tract infections in humans and animals. They are classified into subgroups A through F based on antigenic and genomic properties. Adenoviruses cause localized infection but can cause generalized infection in immunocompromised patients. While there is no highly effective antiviral treatment, adenoviruses have potential as vectors for vaccination and gene therapy by genetically altering them to code for specific antigens or proteins without producing infectious viral offspring.

1. DNA Viruses
Parvovirus B 19
Human papiloma viruses
Adenovirus
Dr Neelam Kaistha
Prof & Head
Dept of Microbiology

2. ADENOVIRUSES

3. Adenovirus
Group of medium sized nonenveloped DNA viruses
Infect humans, animals and birds showing strict host
specificity.
Common worldwide, mostly in children
Cause infection of respiratory tract, eyes and less often
of intestine and urinary tract

4. All mammalian adenoviruses share a common
complement fixing antigen

5. Appearance of a space vehicle

6. Antigenic and genomic
properties
• Grp specific Ag present on inner
surface of hexon capsomer
• Type specific Ag present on the fiber
• 6 grps (A-F)
• Further classified into 51 serotypes

7. Other properties
• Relatively stable
• Remain viable for a week at 37°C
• Inactivated at 50°C
• Resistant to ether and bile salts
• Resist drying,detergents GIT secretions
including acid and protease

8. Pathogenesis
• Transmitted by respiratory or feco-oral
contact from humans
• Multiply in conjunctiva, pharynx or SI
• Spread to preauricular, cervical and
mesentric L Nodes

9. Pathogenesis:
• Adenovirus has a tendency to become
latent in lymphoid tissue,
• The virus can be reactivated by
immunosuppression.

10. Clinical Course
• Incubation Period: 5 to 8 days
• Usually causes a localized infection but
generalized infection can occur in immuno-
compromised patients.
• Responsible for 5% of acute respiratory
childhood illness and 10% of infantile
gasteroenteritis.
• Fatalities ass with human adenovirus type 7.

11. Respiratory diseases
• URT infection in children Serotypes
1,2,3,5
• Pneumonia 10-20% of childhood
pneumonia Serotypes 3,7,21
• Acute respiratory ds syndrome
outbreaks in military recruits serotypes
4 and 7

12. Occular infections
• Pharyngoconjuntival fever- outbreaks in
children summer camps aka swimming
pool conjuntivitis ; serotyes 3 and 7
• Epidemic keratoconjunctivitis or
shipyard eye in adults sero 18, 19 ,37

13. Other infections
• Genitourinary Infections (cervicitis,
urethritis, hemorrhagic cystitis)
• Gasteroenteritis : sero 40, 41
• Some asymptomatic and persistent
infection
• Adenovirus oncogenically tranforms
rodent cells but not human cells.

15. Lab diagnosis
Specimens
• Throat Swabs,
• Nasopharyngeal Aspirate,
• Bronchial Lavage,
• Conjunctival Swab,
• Corneal Scrapings
• Urine
• Faeces

16. Lab Diagnosis cont…
• Direct microscopy- EM-in stool
samples. Serotypes 40,41,42 non-
cultivable
• Enzyme immunoassay,
• Immunofluorescence techniques

17. Lab diagnosis cont...
• Virus isolation in cell cultures--cause
cellular cytopathic effect -- rounded,
swollen cells and basophilic
intranuclear inclusions
• Primary human embryonic kidney cells,
HeLa, Hep-2 cells
• Molecular diagnosis-PCR and DNA
probe

18. Treatment and Therapy
• Antivirals have generally been ineffective
against adenovirus infection.
• Intravenous ribavirin is a potential treatment.
• Adenovirus infection results in long-lasting
immunity against the specific serotype.
• Maternal antibody is protective.

19. Prevention
• Chlorination of swimming pools, drinking
water, wastewater
• High hygiene standards in opthamology
practice
• Hand-washing
• Measures to prevent nosocomial
transmission

20. Vaccination
• Three monovalent vaccine against
adenovirus
• live, oral and attenuated available against 3
serotypes 4, 7, 21
• given orally in gelatin coated capsule and
released in the intestine.
• Mucosal and intestinal immunity result.
• Vaccines are administered to the military but
not available for general use because of
concern about the live vaccine's oncogenic
potential and the level of attenuation
achieved in children.

21. A Successful Vector for
Vaccination and Gene
Therapy
• Adenoviruses have immense potential as
vectors for vaccination and for gene therapy
because adenoviruses can be genetically
altered in vitro to:
• (1) code for specific proteins
(2) not produce infectious, pathogenic viral
offspring.

22. Vaccination:
• A DNA segment that codes for an antigen that stimulates
an immune response in humans can be inserted into the
genome of adenovirus and then inserted into a host.
• Hepatitis B, HIV, herpes simplex, rabies and respiratory
synctial virus regions can be inserted into adenovirus DNA.
• As of April 2021, four adenovirus vector vaccines
for COVID-19 have been authorized in at least one country:
• The Oxford–AstraZeneca vaccine uses the modified
chimpanzee adenovirus ChAdOx1
• Sputnik V uses human adenovirus serotype 26 for the first
shot and serotype 5 for the second.
• The Janssen vaccine uses serotype 26.
• Convidecia uses serotype 5.
• Vaccine for Ebola

23. Gene Therapy
A DNA segment that codes for an enzyme
or protein product that corrects a human
genetic defect can be delivered to the host by
an adenovirus vector.
For example, a normal copy of the defective
gene in cystic fibrosis patients can be
inserted into patients through an adenovirus
vector.

26. Parvoviruses
The name is derived from Latin,
parvum meaning small, reflecting the
fact that B19 ranks among the
smallest DNA viruses.

27. Properties of Parvoviruses
• Structure
– Icosahedral
– Single-stranded DNA, 5.6 kb
– Two proteins
– Nonenveloped
• Classification
– Parvoviridae (vertebrates)
• Parvovirus
• Erythrovirus
• Dependovirus (requires helper virus, such as an
adenovirus)
– Densovirinae (insects)

28. • Replication
– Attachment and entry
– Translocation of viral DNA into nucleus
– Transcription and translation of viral
nonstructural protein and nucleocapsid
– DNA replication
– Virus assembly (nucleus)
– Release from the cell through lysis
Parvoviruses

29. Parvovirus Infections in Humans
• Diseases
– Fifth disease (cutaneous rash)
– Transient aplastic crisis (severe
acute anemia)
– Pure red cell aplasia (chronic
anemia)
– Hydrops fetalis (fatal fetal
anemia)
– B19 virus (It gained the B19
name because it was
discovered in well B19 of a
large series of microtiter plates)
Fifth Disease (parvovirus B19
Slapped Cheek Syndrome)

30. Rash causing childhood Ds
• Measles
• Scarlet fever
• Rubella
• Dukes' disease
• Fifth disease (erythema infectiosum)
• Roseola

31. Fifth Disease
– Targets progenitors of red blood cell
– Pain in joints
– Results in lysis of cells, thus depleting
source of mature red cells leading to
Anemia
– Rarely fatal and without complications

32. • Transient aplastic crisis
– B19 infection of those with other hemolytic anemias
• Sickle cell disease
• Thalassemias
– Can complicate crises
– Sometimes fatal
• Infection of immunodeficient patients
– Can cause persistent infection in bone marrow
– Suppress red cell maturation
– Leads to anemia
• Infection during pregnancy
– Can cause fetal anemia
– Usually not fatal to fetus
Parvovirus Infections in Humans

33. Laboratory Diagnosis
• PCR is most sensitive
– Most useful during viremia
– Otherwise, requires tissue biopsy or bone
marrow tap
• Serological testing for IgM
– Determines recent infection
– IgG testing is not informative

34. Clinical manifestations and lab
diagnosis
Syndrome Host or Condition Clinical Feature Antibody Real time PCR
Erythema
infectiosum
Children (fifth
disease)
Rashes with slapped
cheek appearance
IgM (+ve)
IgG (+ve)
>103 DNA copies/ml
Adults Polyarthropathy
Transient
aplastic crisis
Underlying
hemolytic anemia
Severe acute anemia IgM (-/+)
IgG (-/+)
Initially >1012 DNA
copies/ml, but rapidly
decreases later
Pure red cell
aplasia
Underlying
immunosuppressio
n
Chronic anemia IgM (-/+)
IgG (-/+)
>106 DNA copies/ml
Hydrops fetalis Fetus Fatal anemia IgM (-/+)
IgG (+ve)
PCR is positive
(amniotic fluid)
Quantitation is not
applicable

35. Epidemiology
• B19 virus is common and widespread
• Most adults have been infected
– Mostly subclinical
– IgG is detectable in most healthy people
• Sporadic outbreaks, usually among children,
occur each year
• Transmission from patient to health care staff is
not uncommon
– Role in nosocomial transmission to other
patients

36. Treatment
– Address symptoms
– Transfusions for serious anemic crises
– Commercially-available neutralizing IgG (passive
immunization)
• Prevention and control
– No vaccine available for human parvoviruses
– Good hygienic practices mitigate transmission

37. Papova viruses
• The name derives from three
abbreviations: Pa for papillomavirus, Po
for polyomavirus, and Va for
"vacuolating" (simian vacuolating virus
40 or SV40, which is now known to be
part of the polyomavirus genus).

38. Human Papillomavirus
(HPV)

39. HPV
• HPV is a double-stranded DNA virus 55nm
• Over 100 different strains, more than 30
sexually transmittable
• Selective tropism for epithelium of skin and
mm
• Causes wide range of infection from warts to
Ca cervix

40. HPV Classification
– Low Risk” HPV
•Genital warts
•Low grade cervical dysplasia
•High Risk”HPV
•Low and high
grade cervical
dysplasia
•Cervical Cancer

41. TRANSMISSION
• Close contact
• Sexual contact – main route
• Occasionally a mother with HPV infection --child
intrapartum
• Horizontal transmission between carer and child.

42. • Mean duration of infection varies according to
HPV type and age of infected individual.
• Highest prevalence (≈40%) in females of 20-25
year group

43. GLOBAL BURDEN

44. Contd…

45. In India :
• Cervical cancer- 2nd most common cancer-
22.86% of all the cancer in women
• 12%of all cancers in men and women
• One woman dies of cervical cancer every 8 mins
in India

46. Clinical Features And
Pathogenesis
Cutaneous Warts
• Keratinised epithelium of hands and feet
(younger children and adolescents)
• Feet – HPV -1 and HPV-4
• Flat warts – HPV -3 and HPV -10
• Common warts – HPV- 2,4,7

48. PATHOLOGY
• Histologically- benign with hypertrophy of all
layers of dermis
• Hyperkeratosis of horny layer
• Disappear spontaneously

49. Anogenital Warts
• Condylomata acuminata
• Sexually active adults
• Most common clinical manifestation
• Vulvar and vaginal warts
• Cervical warts

50. Orolaryngeal Lesions
 Recurrent respiratory papillomatosis
• Rare condition
• Benign squamous papillomata on mucosa of
respiratory trac
• t
• Bimodal distribution (children under 5 and
adults over 15 years)
• HPV 6 and 11

51. • Abnormal cry
• Hoarseness of voice
• Recurrence –common
• Malignant conversion – after radiotherapy

52.  ORAL PAPILLOMATOSIS
• Oral mucosa and tongue
• Multiple lesions on buccal mucosa- oral florid
papillomatosis
• Subclinical infection

53. HPV and CANCER
Premalignant Lesions Of Genital Tract
• Cervical intra-epithelial neoplasia (CIN)
• Starts in germinal layer -- surface layers
• Severity from –
• CIN-I
• CIN-II
• CIN-III

54. • CIN-I (low grade squamous intra-epithelial lesions)
• Both low (HPV-6and 11) and high risk types
• Unlikely to progress

55. • CIN-II (high grade /HSIL)
• Abnormal cells or mitotic figures
• Loss of stratification and differentiation
• Progresses spontaneously

56. • CIN-III
• If untreated, progress to invasive cancer

57. Invasive Cancers
• Malignant conversion of skin warts –1/3 of
patients with EV on skin exposed to sunlight
• Oropharyngeal squamous cell cancers(oscc)– HR-
HPV.
• HPV associated OSCC – better prognosis

58. Lab diagnosis
• Histopathology and cytopathology
• Electron microscopy
• Immunocytochemistry
• DNA hybridization and PCR

59. Risk factors
• Immunosuppressed (transplant recepients ,
hematological malignancies)
• HIV infection

60. Prevention
• No “cure” for HPV – prevention most effective
– Regular gynecological exams
– Frequent, proper screening for cervical cancer
• Pap Test (Three years after the onset of sexual
activity)
– Colonoscopy
– Abstinence
– Use of condoms

61. HPV Vaccine
• “Gardasil” vaccine Approved
by FDA on June 8, 2006
• Protects against HPV strains
6, 11, 16, and 18
• Made from non-infectious
virus-like particles (VLPs)
• Cervarix offers immunity
against HPV 16 and 18,
Virus-like particles assembled
from L1 protein of HPV16

63. WHO recommendations :
 Recommended target age and vaccination schedule
• Girls aged 9-14 years* prior to becoming sexually active.
• 2 doses with a 6 month interval.
• no maximum interval between the 2 doses
• If the interval between doses is shorter than 5 months,
then a 3rd dose should be given at least 6 months after the
first dose.
•

64. • 3-dose schedule (i.e.at 0, 1-2, and 6 months)
recommended for-
• Females 15 years and older,
• Immunocompromised and/or HIV-infected (regardless
of whether they are receiving antiretroviral therapy).
Not necessary to screen for HPV infection or HIV
infection prior to HPV vaccination.

65. Polyoma
• Oma- tumour; poly – many
• Non env 40-45 nm
• Simian Virus 40
• JC virus first isolated from brain of male
pt with Hodgkins
• Developed progressive multifocal
leukoencephalopathy
• BK virus

66. Differences between Polyomaviridae and
Papillomaviridae
Characteristic Polyomaviridae Papillomaviridae
Structure 45 nm in size, icosahedral symmetry,
no envelope
55 nm in size, icosahedral symmetry,
no envelope
DNA Circular, dsDNA
Comprises of 5 kbp of nucleotides
Both the DNA strands code for proteins.
Circular, dsDNA
Comprises of 8 kbp of nucleotides
Coding information is present on one
DNA strand
Oncogenic
potential
Transform cells in vitro, but not in vivo
(natural infections )
Can produce tumors in natural hosts
In vitro, rarely transforms cells
Target tissue Internal organs Epithelium (skin & mucosa)

67. Differences between Polyomaviridae and
Papillomaviridae
Characteristic Polyomaviridae Papillomaviridae
Viruses infecting
humans & disease
produced
 JC virus-causes Progressive
Multifocal Leukoencephalopathy
(PML)
 BK virus- causes nephropathy in
transplant recipients. It differs from
JC virus, by its ability to grow in a
wide range of cell lines and is less
oncogenic.
 Merkel cell virus- causes Merkel
cell carcinoma of skin
 SV40 virus (Simian vacuolating 40
virus) is non- pathogen to man
Human papillomavirus ( >100 types)
cause-
 Warts- Skin warts & genital warts
 Epidermodysplasia verruciformis
 Cervical carcinoma and CIN
 Laryngeal papillomas and carcinoma