PARVOVIRIDAE

 the smallest viruses (18- 26 nm size).

 Non-enveloped with icosahedral symmetry.
 linear single-stranded DNA, comprising of about 5000 nucleotides (the only DNA virus to have
ssDNA).
 Capsid is made up of 32 capsomeres.
 Depend upon the host cell enzymes for replication.

Two sub-families
1. Parvovirinae (infect vertebrates) - three genera- Parvovirus, Erythrovirus and Dependovirus
 most pathogenic human parvovirus i.e. Parvovirus B19 belongs to the genus Erythrovirus
2. Densovirinae (infect in sects)

PARVOVIRUS B19
Transmission:
 respiratory route,
 blood transfusion
 transplacental route.

Special tropism for erythiroid progenitor cells present in adult bone marrow and fetal liver; binds 10 blood group P
antigen as receptors; present on the red blood cell (RBC) surface
Results: red cell destruction
inhibition of erythiropoiesis,
profound : underlying immunosuppression
hemolytic anemia.

Clinical Manifestations:
1. Erythema lnfectiosum (children: Fifth disease: slapped cheek, adult women: symmetrical polyardiropathy)
2. Transient Aplastic Crisis
3. Pure Red Cell Aplasia
4. Non-immune Hydrops Fetalis (maximum risk is in the second trimester)

Laboratory Diagnosis
1. Antibody Detection: IgM – early ; indicates recent infection; remains elevated for 2-3 months.
IgG – late.
 Against- conformational epitopes of parvovirus persists for years.
 Against- linear epitopes decline within months.
Antibody may or may not be found in immunodef patients
2. Molecular Methods
PCR - from serum, tissue or respiratory secretions
 Real time PCR (quantification; acute infections- viral load in !he blood may reach 10" DNA copies/ml)
 Genotyping (3 genotypes; antigenically has single serotype; genotype 1- globally common )

Human bocaviruses: with respiratory infection and gastroenteritis in children

Human dependoviruses: adenoassociated viruses (defective and depend on adenovirus for replication) They are non
pathogenic to man.
Family Papillomaviridae: 16 genera
FarnilyPolyomaviridae: several genera infecting animals.
Human infections are associated with : John Cunningham (JC) virus
BK virus
SV40 virus (Simian vacuolating virus 40)

HUMAN PAPILLOMAVIRUS

selective tropism: for epithelium of skin and mucous membranes

Morphology: 50-55 nm
 non-enveloped
 icosahedral capsids ( 72 capsomeres.)
 double -stranded circular DNA
Viral genome:
 early (E) region (El-E7) (early nonstructural proteins)
o E1, E2 - modulate viral DNA replication.
o E6, E7- oncogenic potential
E6 - facilitates -degradation of the p53 tumor-suppressor protein
E7 - binds to the retinoblastoma gene product and related proteins
 a late (L) region (L1, L2- Code for Non structural proteins)
o L1- for major capsid proteins
o L2- minor capsid proteins
 noncoding regulatory region

Pathogenesis

I. Benign Warts
a. Common warts (verruca vulgaris) – young children
b. Flat warts (verruca plana)- children
c. Plantar warts (verruca plantaris) – adolescent, young adults
d. Anogenital warts (condyloma acuminatwn) – STD, adults
II. Epidermodysplasia Verruciformis
a. rare autosomal recessive benign condition
b. can progress to squamous cell malignancy (in sun-exposed areas.)
c. when infected with unique HPV types 5 and 8 (that do not cause any other disease)
III. Cervix Lesions
a. CIN (cervical intraepithelial neoplasia) – benign, low risk HPV types 6 and 11
b. Carcinoma cervix (squamous cell) - high risk HPV types - as 16, 18, 30, 31, 33, and 45
c. High risk associated with sq cell CA - penis, anus, vagina and vulva
IV. Head and Neck Lesions
a. Benign - recurrent laryngeal papillomas – children - low risk types 6 and 11
b. Malignant - laryngeal and esophageal carcinomas - high risk types 16 and 18
V. Pityriasis Versicolor Like Lesions
a. immunosuppressed patients - undergone organ transplantation.
Laboratory Diagnosis
1. lesions are visible to die naked eye - Solutions of 5% acetic acid can be applied to improve visibility
2. Molecular methods : PCR
Hybrid capture assay
 to detect HPV DNA
 to identify specific virus types.
3. Cytological evidence
 Papanicolaou smears (pap smear) prepared from cervical or anal scrapings.
 Histopathological staining of biopsies.

TREATMENT
 Removal of the lesions:
Frequently used procedures for removal of lesions include
 cryosurgery,
 electrodesiccation,
 surgical excision
 laser therapy.
• Topical preparations of
 podophyllum,
 Interferon
 imiquimod (interferon inducer)
can be used for genital warts.
• Recurrence is common.

HPV vaccines
recommended to adolescent and young adult females.
Subunit vaccine - virus-like particles - HPV L1 proteins - produced in yeast by DNA recombinant technology
 Quadrivalent vaccine: serotype 6, 11, 16 and 18 (Gardasil, Merck).
 Bivalent vaccine: high risk serotype 16 and 18 (Cervarix, GlaxoSmithKline)
Barrier methods of contraception - block sexual transmission - prevent anogenital HPV infections.

ADENOVIRIDAE
2 genera : Aviadenovirus: Infects birds

Mastadenovirus: Infects mammals including humans

Human adenovirus – serotyped into 51 distinct antigenic types - divided into six groups (I to VI) – based on:

 Ability to agglutinate RBCs from either monkeys or rats

 oncogenic potential in animals (rats) or cell lines (they are non-malignant to humans)
 Guanine-plus-cytosine (G+C) content of DNA
Group I adenoviruses - serotypes 12, 18 and 31.
maximum oncogenic potential
lowest in G+C content.
only group that does not agglutinate monkey or rat RBCs.
 ADENOVIRUS
Morphology
 70-90 nm
 non-enveloped
 possess 252 capsomeres
 Icosahedral symmetry
 Space vehicle shaped appearance (fiber proteins projecting from each vertex)
 linear dsDNA

Pathogenesis

infect and replicate in the epidielial cell of

 Respiratory tract
 Eye
 gastrointestinal tract
 urinary bladder
 liver

type 1- 7 are the most common types worldwide

Clinical manifestation:

1) Respiratory diseases -1. Upper respiratory tract infection – children – serotypes – 1,2,3,5

2. Pneumonia –10- 20% of pneumonia in childhood - type 3, 7, 21

3. Acute respiratory disease syndrome - military recruit - type 4 and 7

2) Ocular infections: 1. Pharyngoconjunctival fever (swimming pool conjunctivitis)

outbreaks - children's summer camps – type 3, 7

2. Epidemic keratoconjunctivitis (shipyard eye)

adults - highly contagious – type 8, 19 and 37

3) lnfantile gastroenteritis: Serotype 40 and 41 - viral gastroenteritis - young children.

4) Acute hemorrhagic cystitis: children, especially in boys - serotypes 11 and 2
5) Immunocompromlsed: high risk of developing serious pneumonia
6) Transplant recipients: Types 34 and 35

pneumonia, hepatitis, nephritis, colitis, encephalitis and hemorrhagic cystitis.

Laboratory Diagnosis

Specimen:

 throat swab
 conjunctival swab
 stool
 urine
 Antigen detection:
 hemagglutination test
 neutralization test
 Direct-IF test
 electron microscopy and ELISA - Fastidious enteric serotypes - type 40 and 41 from stool
 PCR - type specific antigens
Antibody detection :
 CFT
 neutralization test
 ELISA
 hemagglutination inhibition test (HAI) – rarely
Virus isolation
Most susceptible cell lines:
 Primary human embryonic kidney cell line
 A 549 cell line

Others:

 HEp-2, Hela, and KB cell lines

Viral growth - cytopathic effect - Rounding and grape-like clustering of swollen cells

Antigen detection by direct-IF test.

Shell vial technique - enhance viral replication

Explants culture - esp group-C – in adenoid explants

Treatment and Control – symptomatic

Live adenovirus Vaccine

 containing types 4 and 7 - gelatin coated capsules - orally

 not in use since 1999

Adenoviruses can also be used as live-virus vectors for the delivery of vaccine antigens and for gene therapy.

Genera/Preventive Measures

 Effective hand washing.

 Use of paper towels is better than cloth towels for hand drying which easily get dirty.
 Sodium hypochlorite to disinfect environmental surfaces.
 Chlorination of swimming pools and waste water should be followed to prevent waterborne
conjunctivitis or gastroenteritis.
 Strict asepsis during eye examinations
 POXVIRIDAE
Morp:
 Poxviruses are the largest - seen under light microscope
 Most complex viruses - structure does not 6t into either icosahedral or helical symmetry
 Brick-shaped or ellipsoid
 envelope - made up of two lipoprotein membranes -envelope encloses a core and two structures of unknown
function called lateral bodies
 Core or the nuclecapsid - biconcave dumbbell shaped - surrounded by a core wall.
 Capsid - 12 nm thick - more than 1000 capsomers - encloses single linear dsDNA and many enzymes including
transcriptases.
 only DNA virus that replicates in the cytoplasm.

Classification

 eight genera
 human infections - four genera.

SMALLPOX VIRUS (VARIOLA)

first disease - eradicated from the world
highly contagious severe exanthema (rashes)
Currently, only two laboratories still hold stocks of smallpox virus:
1) CDC (Centers for Disease Control and Prevention) Atlanta (USA).
2) Center for Research on Virology and Biotechnology, Koltsova (Russia).
potential agent of bioterrorism.
Eradication: 8th may, 1980
 exclusively human pathogen, no animal reservoir
 source – patients ; no carrier
 diagnosis – easy - characteristic appearance of rashes
 Subclinical cases- no transmit the disease
 Highly effective live vaccinia vaccine

Manifestation:
 entry - mucous membranes of the upper respiratory tract.

Incubation period: 12 days (7- 17 days).

Rashes:

o deep seated
o all rashes in an area appeared in one stage,
o evolution was slow
o Centrifugal distribution (palm and sole and extensor surface were affected first)
o Fever subsided with appearance of rash.
Lab findings:
scrapings from rashes:
lntracytoplasmic inclusion bodies (Paschen bodies).
Electron microscopy: Brick-shaped appearance with biconcave DNA core.
Egg inoculation: Characteristic pock formation - on chorioallanroic membrane (CAM) of a chick embryo

Treatment: - • Vaccinia lmmunoglobulins

• Antiviral drugs such as methisazone and cidofovir

Vaccination:
live vaccinia vaccine : un-anenuated live virus
o 1 and 2 years of age.
o adr were common - mild vaccinia induced rashes.
Cowpox vaccine - discovered by Edward Jenner (father of vaccination)
Variolalion – first attempt of providing artificial immunity against smallpox
o Healthy people were inoculated with 1he skin scraping of a smallpox patient

VACCINIA VIRUS
cross-reacts with variola - antibodies produced against vaccinia are protective for variola - vaccinia was able to eradicate
variola globally.

How vaccinia differs from variola?

o non-padiogenic 10 humans / produces milder skin lesions
o Produces an inclusion body called Guarnieri body (variola produces Paschen body).
o CAM, vaccinia - larger and hemorrhagic and necrotic pock lesions than variola
o Ceiling temperature: vaccinia virus (41°C) ; variola virus (38°C).
o Vaccinia can produce plaques on chick embryo tissue cultures (variola cannot)

MOLLUSC UM CONTAGIOSUM VIRUS

obligate human pox virus - produces characteristic skin lesions.

Clinical manifestation:

o Lesions:
 pink pearly wart-like lesions
 (2-5 mm size)
 Umbilicated
 characteristic dimple at the center
 Lack of associated inOamma1ion and necrosis
 singly or in clusters
 found anywhere on 1he body except on die palms and soles
 Genital lesions are seen in adults.

o Transmission:
 Children are commonly affected
 by direct and indirect contact
 eg: barbers, common use of towels, swimming pools
 sexual transmission – young adults – rare
o Self-limitting:
 Lesions disappear in 3-4 months
 no systemic complications
 sometimes, lesions may persist for 3-5 years.
o ln HIV-infected patients:
 Disease i5 more generalized, severe and persistent.

Lab:

o skin scrapings - stained with histopathological stain – intracytoplasmic eosinophilic inclusions

o confirmation by : Electron microscopy and PCR
o not cultivable: cannot be propagated in tissue culture, egg or in animals.

Treatment:

o Surgical removal of the lesions by ablation

o CIDOFOVIR - some efficacy
o does not cross-react with any other poxviruses - smallpox vaccine is not protective