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Virus

Herpes Simplex
Virus
(Herpesviridae)

Varicella Zoster
Virus
(Herpesviridae)

Cytomegalovirus
(Herpesviridae)

DNA VIRUSES
Characteristics
Icosahedral
Enveloped
Double stranded
linear
2 types: HSV-1 and
-2
Lifelong infection

Icosahedral
Enveloped
Double stranded
linear
Lifelong infection
Primary and
Recurring
disease

Icosahedral
Enveloped
Double stranded
linear
Recurrent infection
Congenital
infection

Epidemiology
Spread: direct
contact (orally or
sexually)
Location: neurons
and epithelia
(latency)
Risk Factors:
1. Contaminated
fingers
2. Birth canal
transmission
3. Kissing
At Risk:
1. Children and
sexually active
people
2. Health care
workers
3. Immune
compromised or
neonates
Spread: respiratory
droplets
Location: neurons
and epithelia
(latency)
At Risk:
1. Children (5-9yo)
2. Teens and adults
3. Immune
compromised or
neonates

Spread: saliva, body

fluids
Location:
monocytes and
macrophages
(latency)
Risk Factors:
1. Immunocomp
2. Giving birth
3. Sexual
intercourse
4. Blood transfusion

Pathogenesis and Virulence

Pathogenesis
1. Skin penetration and replication
2. Enters cutaneous sensory neurons
and ascends to ganglia to establish
latency
3. Virus can be reactivated and can travel
via neurons recurrent infection
Virulence
1. Direct cytopathologic effects
2. Syncytia formation: cell-cell spread,
avoids antibodies
3. Latency in neurons!!
4. CMI is required for resolution
HSV-1: trigeminal ganglia to nasooral epithelia
HSV-2: sacral ganglia to urogenital
epithelia
Pathogenesis
1. Initial respiratory infection
2. Viremia: spread of virus to nerves and
skin
3. Establish latency in DRG or CN ganglia
4. Reinfection spreads along dermatome
5. Vesicle progression: macule papule
vesicles pustules crusts
Virulence
1. Viremia
2. Escape Ab clearance
3. Latency!

Pathogenesis
1. Initial infection through blood
(monocytes and macrophages)
2. Establish latency in infected
macrophages
3. Primary infection is subclinical
(asymptomatic)
Virulence
1. Viremia
2. Latency

1
Diseases
1. Herpes gingivostomatitis: initial
primary infection
2. Herpes labialis or Cold sores:
painful shallow ulcers on lips
accompanied by fever, malaise and
myalgia; usually heal without scarring in
8 to 10 days
3. Herpetic whitlow: thumb lesion
4. Keratoconjunctivitis: corneal scarring
and blindness (2nd most common cause)
5. Encephalitis: if virus spreads to CNS

Lab Diagnosis
Visual
diagnosis
Tzanck
smear: multinuc giant cells
and cowdry A
inclusion
bodies
Cell culture
Serology: type
specific Ab
(HSV-1 vs -2)

Treatment
Acyclovir
Foscarnet

Same as HSV

VarizIg
neutralizing
Ab
Live
attenuated
vaccine:
children

Owls eye
inclusion
body
Serology: Ag
detection
PCR
Absence of
atypical
lymphocytes
and
heterophile Ab

Ganciclovir
Foscarnet
Screening
reduces
intrauterine
transmission

Risk for Reactivation:

1. Stress (UV, emotional)
2. Immune suppression
3. Spicy/ acidic food
4. Menstruation
5. Fever

Varicella (Chicken Pox)

1. mild asymptomatic disease - fever,
maculopapular rash
2. Within hours, each lesion turns into
thin-walled vesicle (glue drop on rose
petal)
3. Vesicle (hallmark!): Rash spreads
from trunk; reaches scalp
4. Itchy lesions scratching invites
secondary bacterial superinfection
Herpes Zoster (Shingles)
1. Severe pain precipitates lesions
2. Spread along dermatome
3. Post-herpetic neuralgia: chronic pain
after infection
1. Infectious mononucleosis:
common infection of adults; fever,
muscle pain, lymphadenopathy (similar
to EBV IM)
2. Cytomegalic Inclusion disease:
infection during pregnancy; small
baby, microcephaly, jaundice, hearing
loss, mental retardation, cataracts
3. Multisite symptomatic disease: often in
immune compromised; pneumonia,
meninigitis, hepatitis, encephalitis, failed
renal transplant

DNA VIRUSES

sl 2013

Epstein-Barr
Virus
(Herpesviridae)

Parvovirus
(Parvoviridae)

Adenovirus
(Adenoviridae)

Icosahedral
Enveloped
Double stranded
linear
Linked to
malignancy

Icosahedral
Non-enveloped
Single stranded
linear
Smallest virus

Icosahedral
Non-enveloped
Double stranded
linear
50 serotypes
Used as a vector
for gene therapy

At Risk:
1. Neonates
2. Sexually active
people
3. Immune
compromised
4. Burn victims
Spread: saliva, body
fluids
Location: memory
B cells (latency)
At Risk:
1. Teenagers
2. Children
3. Immune
compromised

Spread: respiratory
Location: erythroid
progenitor cells
Risk Factors:
1. Sickle cell disease
2. Pregnancy (first
trimester highest
risk)
At Risk:
1. Elementary
school students
2. Parents of
children with B19
Spread: respiratory
and feco-oral
Location: intestine,
eyes, respiratory
tract
Risk Factors:
1. Contaminated
hands
2. Ophthalmologic
instruments
3. Swimming water
At Risk:
1. Infants

Pathogenesis
1. Initial replication in oropharynx
2. Infect B cells via C3b receptor
3. Establishes latency
4. Virus replicates when B cells
replicate
5. T cells try to eradicate B cells
Virulence
1. Latency
2. Immortalization of B cells
3. Polyclonal B-cell proliferation
4. T cell activation leads to disease
manifestation (IM)

1. Viremia: high titer virus infection lasting

1 week after infection
2. Infection of rapidly dividing cells
primarily erythroblasts
Two phases:
1. Initial Viremia
2. Immune Response: immune complex
deposition

1. Enters cell via receptor-mediated

endocytosis
2. Inactivates p53 and Rb
3. Shuts off DNA, RNA and protein
synthesis
4. Release of infected virus comes from
disintegration of dying cell

1. Infectious mononucleosis: fever,

myalgia, splenomegaly and
lymphadenopathy (same as CMV)
2. Burkitt Lymphoma: translocation
of c-myc gene on chrom 8 to Ig heavy
chain gene on chrom 14; malignancy
of jaw
3. Hairy Oral Leukoplakia: EBV infection
on epithelium lesions on mouth; full
blown AIDS
4. EBV-associated nasopharyngeal
carcinoma
5. EBV infection for
immunocompromised: can sufficiently
cause B cell lymphomas
1. Flu-like symptoms: Initial consequence
of early phase viremia
2. Erythema infectiousum or 5th
disease: slapped-cheek rash on the
face due to immune complex
deposition
3. Aplastic crisis in individuals with
chronic anemia (sickle cell): fever,
chills, malaise, itching, rash
4. Polyarthritis: symptoms in many joints

1. Acute febrile pharyngitis: strep

throat-like in children and infants
2. Pharyngoconjunctival fever: pharyngitis
and conjunctivitis
3. Acute respiratory disease: military
recruits
4. Pertussis-like syndrome: infants and
young children; use the cough-plate
method
**All can progress to pneumonia
5. Meningoencephalitis
6. Keratoconjunctivitis: inflamed
pebbled conjunctiva; transmission by

CBC:
lymphocytosis
Atypical
lymphocytes
Heterophile
Ab
Paul-Bunnell
Test
EBV specific Ag
1. EA first
Ab
2. VCA IgM
then IgG
3. EBNA
marker of
infection; last
to develop
Clinical
presentation
ELISA IgM
PCR

No vaccine
Acyclovir?

ELISA
PCR
culture

Live vaccine for

serotypes 4 &
7 given to
military
personnel
Serology
neutralization

No antiviral
agent or
vaccine
IVIG for B19
virus in
immunocomp

DNA VIRUSES

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2. Military
recruits low
resistance to virus &
exposure to new
strains

Human
Papilloma Virus
(HPV)
(Papovaviridae)

Human
Polyoma Virus
(Papovaviridae)

Variola Virus
(Poxviridae)

Icosahedral
Non-enveloped
Double stranded
circular
High risk for
cervical
carcinoma (HPV
16 and 18)

Spread: sexual
contact, fomites,
transplacental
Location:
differentiated
epithelial cells
Risk Factors:
1. Pregnancy
2. Unprotected sex

1. Infects epithelial cells and its

differentiation state (cutaneous epithelia
or mucosal epithelia) tropism,
permissivity and immortalizing
infection
2. Access to epithelial cells is most likely
due to surface lesions (abrasions)
3. Wart formation: papillomavirus early
proteins facilitate migration of virus
from basal layer to surface
4. Carcinoma: binding between early
proteins and p53 and Rb increases risk
of malignancy, require integration of
viral genome in host chromosome

Icosahedral
Non-enveloped
Double stranded
circular
Three human
subtypes: JC, BK,
& MC

Spread: respiratory
and urine
Location: CNS,
urinary tract
Risk Factors:
1. Immune
compromised
At Risk:
1. Children

1. Spread from URT to kidneys (inactive

state)
2. Reactivation: viral replication, cell death
and viral release

Complex
Enveloped
Double stranded
linear
Eradicated from
Earth

Spread: none
Risk Factors:
1. Mutations in
animal poxviruses
At Risk:
1. Unvaccinated

Other Medically Important DNA Viruses

HHV 6 Roseola
HHV 8 Kaposis Sarcoma

JC virus:
1. Viremia: spread to CNS
2. Reactivated in oligodendrocytes
3. Demylination
BK virus: UTI in immunocompromised
1. Replication in cytoplasm: rapid, shuts
off cell synthesis and leads to cell death
and viral release

3
sharing of towels, unsterilized ocular
instruments
7. Gastroenteritis: infantile diarrhea
with vomiting (5-15% of viral diarrhea
in children); serotypes 40-42
8. Acute hemorrhagic UTI: bone marrow
recipients
9. Hepatitis: liver transplant recipients
1. Skin warts (types 1-4): keratinized
surface, benign and self-limiting,
regresses with time; mainly on hands,
fingers and feet; could lead to
squamous cell carcinoma
2. Laryngeal papilloma (types 13 & 32):
benign; due to infection of oral and
nasopharyngeal mucosa
3. Anogenital warts/Condyloma
accuminata (mostly type 6 & 11): benign
growth on squamous epithelia
4. Cervical cancer (type 16, 18):
carcinoma in situ, integrate into host
chromosome; E6/E7: inactivate p53
and Rb; E5: enhances EGF
1. Progressive multifocal
leukoencephalopathy (JC): mental
and sensory abnormalities, paralysis and
impared speech
2. UTI (BK)

Secondary infections

Visual
inspection
PCR: determine
whether HPV
is high risk

Gardasil: vaccine
against HPV 6,
11, 16 and 18
Surgical removal
or destruction
of warts

Most people
have Ab to
viruses
DNA
hybridization

No preventive
measures

None

Smallpox
vaccine
**Post-vaccinal
encephalitis
can occur