NONENVELOPED DNA VIRUSES

PAPOVAVIRIDAE

Human Papovaviridae and Their Disease

Clinical Syndromes Associated with Papillomaviruses

Unique Properties of Papovaviruses HPV TYPES
 There is a small icosahedral capsid virion. SYNDROME COMMON UNCOMMON
SKIN WARTS
 Double-stranded circular DNA genome is replicated and
assembled in the nucleus. Plantar wart 1 2,4
 These are two major genera: Common wart 2,4 1,7,26,29
o Papilloma: HPV types 1 to 58+ (as determined Flat wart 3,10 27,28,41
by genotype; types defined by DNA homology, Epidermodysplasia 5,8,17,20,36 9,12,14,15,19,21-
tissue tropism, and association with verruciformis 25,38,46
oncogenesis) BENIGN HEAD AND
o Polyoma: SV-40, JC virus, and BK virus NECK TUMORS
 Viruses have defined tissue tropisms determined by Laryngeal papilloma 6,11 -
receptor interactions and the transcriptional machinery Oral papilloma 6,11 2,16
of the cell Conjunctival 11 -
 Viruses encode proteins that promote cell growth by papilloma
binding to the cellular growth-suppressor proteins p53 ANOGENITAL WART
and p105RB. Polyoma T antigen binds to p105RB and Condyloma 6,11 1,2,10,16,30,44,45
p53. E6 binds to p53, and E7 binds to p105RB. acuminatum
 Viruses can cause lytic infections in permissive cells but Cervical 16,18. 11,31,33,35,42-44
cause abortive, persistent, or latent infections or intraepithelial
immortalize (transform) nonpermissive cells. neoplasia, cancer

Disease Mechanisms of Papovaviruses Verruca vulgaris. Common warts are

typically single or multiple, flesh
colored, dome-shaped papules with
a rough, verrucous surface. They can
occur anywhere on the skin but are
most common on exposed surfaces
such as the fingers, hands, feet and
face.

Common warts with thrombosed vessels (black

dot) on the surface.

Verruca plantaris. Plantar warts occur on

weight bearing areas of the feet and
commonly exhibit overlying hyperkeratosis.
Note the punctuate dark brown dots which
represent vessel thrombosed in the superficial
dermis.

Verruca lanta. Flat warts occur primarily on

the face and extremities. They are generally
small, flesh or brown-colored, broad based
papules varying in number. Autoinoculation
from trauma, such as shaving, is a common
means of viral spread.

Epidemiology of Papovaviruses
Condyloma acuminate. It is
characterized by soft, flesh-
colored polypoid or acuminate
warts that occur in the
anogenital region. It can be
extensive and cause pain, itching
and bleeding.

Laboratory Diagnosis of Papilloma Infections

 Disease Mechanisms of Adenoviruses

DNA probe analysis of

an HPV-6-induced
anogenital condyloma
Dark staining is seen
over nuclei of
koilocytic cells.

Mechanism of spread of polyomaviruses within the body.

Time Course of Adenovirus Respiratory Infection

Laboratory Diagnosis of Polyomavirus (JC and BK Infections)

TEST DETECTS
Pap smear of urinary epithelial Viral inclusions
cells
Electron microscopy Virions
Immunofluorescence and Viral antigens
immunoperoxidase staining Epidemiology of Adenovirus
DNA probe analysis Viral nucleic acids
Nucleic acid hybridization in BK and JC viruses
clinical specimens Nucleic acids
Cell culture
Human diploid lung fibroblasts Virus isolation-BK
Primary human fetal glial cells Virus isolation-JC

ADENOVIRIDAE

Unique Features of Adenoviruses

Illness Associated with Adenoviruses Disease Mechanisms of B19 Parvovirus
ILLNESS CATEGORY MOST COMMON SEROTYPES Mechanism of Spread of parvovirus within the body
Endemic respiratory disease 1,2,5
Acute respiratory disease of 3,4,7,14,21
military recruits
Adenoviral pneumonia 3,4,7b,14,21
Epidemic keratoconjunctivitis 8,19
Pharyngoconjunctival fever 3,7
Less common syndromes
Pertussis syndrome 1,2,3,5
Acute hemorrhagic cystitis 1,4,7,11,21
Hepatic disorders 3,7
Gastroenteritis 9,12,13,18,25-29, 40-42
Intussusception 1,2,5
Musculoskeletal disorders 7
Genital infections 19
Skin infections 2,4,7,21
Infections in immuno- 32,34-36
compromised hosts

Adenovirus conjunctivitis. Adenoviral

exanthems are frequently generalized
and nonspecific. Other associated
findings include fever, rhinitis,
pharyngitis, adenopathy and
conjunctivitis.
Time course of parvovirus (B19) infection. B19 causes biphasic
disease: first, an initial, lytic infection phase characterized by
febrile, influenza-like symptoms and then a noninfectious
immunological phase characterized by a rash and arthralgia.

(Insert time course picture)

Epidemiology of B19 Parvovirus Infections

Hematoxylin and eosin-
stained sample of adenovirus.
Pneumonia, showing
inflammation, necrosis and
exudates.

PARVOVIRIDAE

Unique Properties of Parvoviruses

A slapped-cheek appearance is typical

of the rash for erythema infectiosum.

Erythema infectiousum. The third stage of

Fifth’s disease begins as the rash starts to
fade with areas of central clearing. This
leaves a reticulated or lacy pattern of
erythema which can last several weeks. The
most common complication is join
involvement ranging from mild arthralgias to
overt arthritis.
NONENVELOPED DNA VIRUSES

HUMAN HERPESVIRUSES

Properties Distinguishing the Herpesviruses

Unique Features of Herpesviruses Epidemiology of HSV Infection

HERPES SIMPLEX VIRUS 1 AND 2

Disease Mechanisms for Herpes Simplex Virus

Clinical course of genital herpes infection. The time course and
symptoms of primary and recurrent genital infection w/ HSV-2 are
compared.
Disease syndromes of HSV. HSV-1 and HSV-2 can infect the same tissue and
cause similar diseases but have a predilection for the sites and diseases
indicated.
 Primary herpes gingivostomatitis
is the most common herpes
simplex virus-1 infection in FDA-Approved Antiviral Treatments for Herpesvirus Infections
children. Vesicles, erythema
and swelling occur in the oral
HERPES SIMPLEX VIRUS 1 AND 2
cavity and on the lips. Erosion of
vesicles leave small shallow
Acyclovir
ulcers on an erythematous base. Adenosine Arabinoside
Iododeoxyuridine
Trifluridine

VZV
Cold sore of recurrent herpes labialis. Acyclovir
Varicella-zoster immune globulin (VZIG)
Zoster immune plasma

EBV
Herpatic whitlow is
None
characterized by inoculation of
the HSV virus into the skin of CMV
one or more fingers causing Ganciclovir
painful superficial or deep Foscarnet*
vesicles or bullae with a whitish
blue-hue. *ALSO INHIBITIS HSV AND VZV

Herpetic coneal ulcer. Corneal

infection due to HSV is VARICELLA-ZOSTER VIRUS
characterized by dendritic ulcers
which are branching morphologic Disease Mechanisms of VZV
appearance of the lesions.
Recurrent infections can lead to
scarring and impairment of
vision.

Eczema herpticum (Kaposi’s

varicelliform eruption). Note the
vesicles, superficial ulcers and crusts
in the antecubital fossa of this toddler
with atopic dermatitia.

Genital Herpes. It begins as vesicles

or pustules which progress to
erosions and ulcers, generally
lasting 1-3 weeks. Associated local
symptoms for both primary and
recurrent genital HSV infections Mechanism of spread of VZV within the body
include severe pain, itching, dysuria, inguinal adenopathy and urethral or
vaginal discharge.

Neonatl herpes. Newborns may acquire

primary herpes simplex virus (HSV)
infection in utero, during delivery or
postnatally. Cutaneous involvement
may be minimal or extensive and is not
necessarily indicative of the severity of
concurrent systemic disease.

Laboratory Diagnosis of HSV infections

Time course of varicella (chickenpox)

Tzanck stain of
herpetic vesicle. Note
the large
multinucleated giant
cell. The preparation
is obtained by
scraping the base of a
new, freshly opened
vesicle and staining
with Giemsa stain or
toluidine blue.
Epidemiology of VZV Infection

Acute herpes zoster. After primary varicella-

zoster virus infection, the virus persists in a
latent form and can be reactivated, resulting in
herpes zoster or “shingles”. Herpes zoster is
characterized by papules, vesicles and pustules
on an inflammatory base in a dermatomal
distribution, frequently associated with burning
pain and tenderness.

Varicella. After an incubation

period of approximately 14-16 days
the disease begins with low grade
fever, malaise and the appearance
of a characteristic generalized
pruritic vesicular Eruption
(“dewdrop on a rose petal”).
Tzanck stain of the contents of a
varicella vesicle. Note the
multinucleated giant cells. These
represent swollen epidermal cells
Characteristic skin rash of varicella containing intercytoplasmic viral inclusion.
demonstrating all of the stages of
evolution of the rash.
EPSTEIN-BARR VIRUS

Disease Mechanisms of Epstein-Barr Virus

Varicella in a child. The eruption generally

begins on the trunk or head and spreads
centrifugally. New lesions generally begin
to crust within 1-2 days. It is common to
find various-sized papules, vesicles,
pustules and crusts all present on the skin
at the same time.

Varicella in an
adult. Over
90% of primary
varicella infections occur in children. In
adolescents, adults and immunocompromised
patients, the disease can be more severe.
Secondary bacterial skin infections, otitis
media, pneumonia, encephalitis, hepatitis and
Reye’s syndrome are well known complications
of varicella infection.
Pathogenesis of EBV. EBV is acquired by close contact between persons
through saliva and infects the B cells. The resolution of the EBV infection
and many of the symptoms of infectious mononucleosis result from the
activation of T cells in response to the infection.

Differences between Chickenpox and Smallpox

Chickenpox Smallpox
Distribution Relative density is Relative density is
centripetal. centrifugal

Predominance on flexor Predominance on extensor

surfaces and flexures surfaces and prominences
Mode of Lesions appear in crops Lesions progress from stage
Evolution to stage synchronously
Time of Rapid Relatively slow
evolution
Lesions Superficial Deep set

Ova or totally irregular Tend to be circular and

regular

Unilocular Vesicles multilocular

Scarring slight and Scarring severe and deep

superficial
Cellular Antigens Associated with EBV-Infected Cells
NAME ABB. CHAR. BIO. ASSOC. CLIN. ASSOC.
EBV nuclear EBNA Nuclear EBNA is a Anti-EBNA
antigen nonstructural develops late
antigen and is in infection.
the first
antigent to Serological Profile for EBV Infections
appear; EBNA
is seen in all
infected
transformed
cells, and it
binds to cell
DNA.
Early EA-R Only EA-R appears Anti-EA-R is
antigen cytoplasmic before EA-D; seen in
its appearace Burkitt’s
is the first lymphoma.
sign that an
infected cell
has entered
lytic cycle.

EA-D Diffuse in - Anti-EA-D is

cytoplasm seen in
and nucleus infectious
mononucleosis.
Viral capsid VCA Cytoplasmic VCA is a late Anti-VCA IgM is
antigen antigen; it is transient; anti-
found in virus VCA IgG is
producer persistent.
cells.
Lymphocyte- LYDMA - LYDMA is not LYDMA is not
defined found on detectable by
membrane Burkitt’s antibody.
antigen lymphoma
cells; iti s
found on cells
infected in
vitro, and is
found on
nonproducer
cells
Membrane MA Cell surface MAs are the Same as VCA.
antigen envelope Clinical course of infectious mononucleosis and laboratory findings of those
glycoproteins with infection. EBV infection may be asymptomatic or produce the
Heterophile Recognition EBV-induced Early symptoms symptoms of mononucleosis. The incubation period can last as long as 2
antibody of Pul- B-cell occur in more months.
Bunnell proliferation than 50% of
antigen on promotes patients. Papular acrodermatitis of childhood Gianolti-
sheep, production of Crosti disease) – a distinctive erythematous,
horse, or heterophile discrete popular eruption that is acrally
bovine antibody. located with relative sparing of the trunk.
erythrocytes Associated findings may include
lymphadenopathy, hepatomegaly and
Epidemiology of Epstein-Barr Virus Infection

evidence of hepatitis.

Ampicillin rash in a patient with

infectious mononucleosis when
antibiotics (usually ampicillin)
are administered during primary
EBV infection, a red or copper
colored morbilliform eruption
may appear. The rash begins on
the trunk and gradually spreads
over the entire body.
 Lymphoid system Mononucleosis syndrome, Leukopenia,
Hairy leukoplakia caused by EBV. posttransfusion syndrome lymphocytosis
Major Organs Carditis, hepatitis Hepatitis
Neonates Deafness, mental -
retardation

Atypical T-lymphocyte (Downey cells)

Congenital cytomegalovirus (CMV)
characteristic of infectious
infection. Cutaneous rash is unusual in
mononucleosis.
acquired CMV infections but is common in
congenital CMV infections. Congenital CMV
may range from asymptomatic to profound
with systemic manifestations including
intrauterine growth retardation,
CYTOMEGALOVIRUS hepatosplenomegaly, pneumonia,
neonatial jaundice, thrombocytopenia,
Disease Mechanisms of CMV central nervous system involvement and
chrioretinits. Skin findings include purpuric
paules and nodules.

Clinical course of CMV infection

Epidemiology of Cytomegalovirus Infection Laboratory Tests for Diagnosis of CMV infection

CMV-inefcted cell with basophilic nuclear inclusion body.

HERPESVIRUS 6

Roseola infantum or exanthum subitum is a

common exanthema of childhood caused
by infection with human herpesvirus 6. It
is characterized by a febrile illness with
mild constitutional symptoms lasting 3-5
days. After rapid defervescence, a pink
macular or maclopapular rash appears
CMV Syndromes primarily on the trunk and lasting hours to
TISSUE CHILDREN/ADULTS IMMUNOSUPPRESSED days.
PATIENTS
Predominant Inapparent infection Disseminated disease,
nature of disease (prominent presentation severe disease
of disease
Eyes - Chorioretinitis
Lungs - Pneumonia
Gastrointestinal - Esophagitis, colitis
tract
Nervous system Polyneuritis, myelitis Meningitis and
encephalitis, myelitis
POXVIRIDAE

Unique Properties of Poxviruses

Properties of Smallpox that Led to Its eradication

Disease Mechanisms of Poxvirus

Diseases Associated with Poxviruses

Spread of Smallpox within the body.

Discrete vesiculopustular
stage of smallpox. Smallpox
(variola) is a highly contagious
disease cuased by Poxvirus
variolae, which apparently
has been eradicated from the
world.

Molluscum contagiosum is a
common, benign viral infection of
The virus enters and replicates in the respiratory tract without causing the skin and mucous membranes
symptoms or contagion. The virus infects macrophages, which enter the characterized by distinct single or
lymphatic system and carry the virus to regional lymph nodes. The virus multiple dome-shaped papule
then replicates and initiates a viremia, causing the infection to spread to which are flesh or pink colored.
the skin (rash). A secondary viremia causes the development of additional Central umbilication can occur.
lesions throughout the host, followed by death or recovery with or without
sequelae. Recovery was associated with prolonged immunity and lifelong
protection.
Skin lesion of molluscum contagiosum.
Time Course of Smallpox Infection

Vaccinia. Three to 5 days after

primary inoculation with vaccinia
virus. A vesicle forms, followed by
a pustule, which increases in size
for 9-10 days and then heals
leaving a scar. Severe localized erythema may occur at the injection site.

Orf Lesion on finger of taxidermist.

Microscopic view of
molluscum contagiosum.
Epidermis filled with
molluscum bodies.

Wright’s stain of the extruded

contents of a molluscum papule.
Note the blue stained viral
inclusions (molluscum bodies)
within the cytoplasm of epidermal
cells.