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DNA ENVELOPED AND NONENVELOPED VIRUSES
Microbiology
Medical Notes by: John Lorenz Beleno, RM, RN, MD

MICROBIOLOGY: DNA ENVELOPED AND NONENVELOPED VIRUSES

Herpesvirus family contains SIX important human pathogens
o Herpes simplex virus 1
o Herpes simplex virus 2
o Varicella-Zoster virus
o Cytomegalovirus
o Epstein Barr Virus
o Human Herpes Virus 8 (Kaposi’s Sarcoma)
•
Some information is available regarding the mechanism of the
latent state
...

o Shortly after HSV infects neurons, a set of “latencyassociated transcripts” (LATS) are synthesized
...

o The precise mechanism by which they do so is
unknown
...

o CMV establishes latency by producing microRNAs that
inhibit the translation of mRNAs required for viral
replication
...

o Inhibition of apoptosis allows the infected cell to
survive
• Herpes viruses are noted for their ability to cause latent
infections
o Patient is infected to cause acute disease; followed by
quiescent and latent period
o To exposed to an inciting agent or triggering factor or
immunosuppression
o Reactivation of replication disease
•
With some, symptoms of subsequent episodes are similar to
those of the initial one
o E
...
Herpes simplex virus—looks like vesicles on the
skin
o With others, they are different [e
...
VZV: primary
manifestation is vesicle but when the virus undergo
latency and then reactivation, the manifestation is
different] [limited to dermatome]
•
Some information is available regarding the mechanism of the
latent state (review)
CHARACTERISTICS
•
Three of the herpesviruses cause a vesicular rash
o HSV1 and 2, VSV
•
Primary infections more severe than reactivation
•
Four herpesviruses induce the formation of multinucleated
giant cells
o HSV 1 and 2
o VZV
o CMV
DIAGNOSIS
Tzanck smear: reveals the multinucleated giant cells
▪
Smear taken from painful vesicles of the genitals
▪
Herpes simplex type 2

3 categories:
1
...
HSV 1 and 2
b
...
Infect epithelial cells
d
...
Beta:
a
...
HHV-6
c
...
Gamma
a
...
HHV8
c
...
Antigenecity
2
...

HSV-1 and HSV-2 can be differentiated by
o Restriction endonuclease patterns of genome DNA
o Type specific monoclonal antisera [serologic test]
HSV-1 and HSV-2 are structurally and morphologically
indistinguishable

TRANSMISSION AND EPIDEMIOLOGY
TRANSMISSION
•
HSV-1
o Primarily in saliva
o Infections mainly on the face
•
HSV-2
o Sexual contact

1

HERPESVIRUSES
•

CLASSIFICATION
•
Herpes virus family can be subdivided into THREE
categories based on:
1
...
Site of latency

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DNA ENVELOPED VIRUSES

MICROBIOLOGY: DNA ENVELOPED AND NONENVELOPED VIRUSES

Herpes Labialis
The milder recurrent form
AKA: Fever blister or cold sores
Characterized by crops of vesicles, usually at the
mucocutaneous junction of the lips or nose

3
...

•
•

Encephalitis
Characterized by a necrotic lesion in the temporal lobe
Clinical features:
o Fever
o Headache
o Vomiting
o Seizures
o Altered mental status
Typical findings in CSF
o Expect alterations in sugars, protein
o Mostly high neutrophils in bacterial meningitis

PATHOGENESIS
•

Upon primary infection, the virus replicates in skin, mucous
membranes
After the infection, migrates UP the neurons [retrograde
axonal flow]
Latent in sensory ganglion cells
Reactivated by a variety of inducers
Virus, then, migrates DOWN the neuron
Then replicates in the skin [lesions] for the second time

•
•
•
•
•

LATENCY PERIOD
•
HSV-1 becomes latent in the sensory ganglion cells
•
HSV-1: Trigeminal ganglia
•
HSV-2: Sacral ganglia
REACTIVATION
•
The virus can be reactivated by a variety of inducers:
o Sunlight
o Hormonal changes
o Trauma
o Stress
o Fever
MANIFESTATIONS
•
The typical skin lesion is a VESICLE
o Serous fluid filled with virus particles and cell debris
o Classic description: seen in groups or CROPS
PATHOLOGY
•
Multinucleated giant cells are typically found at the base of
the lesions
...

Both reinfection and reactivation occur in the presence of
circulating IgG
o Immunity is incomplete
o Means if you get the infection it doesn’t mean you
will not get it again
Cell-mediated immunity is important in limiting
herpesviruses
...

•
•
•
•

causes several forms of primary and recurrent diagnosis
Gingivostomatitis
Occurs primarily in children accompanied by fever,
irritability and vesicular lesions of the mouth
The primary disease is more severe and lasts longer than
the recurrence
Heal spontaneously in 2-3 weeks
Many have asymptomatic primary infections

•

5
...

•

Herpes gladiatorum
occurs in wrestlers and others who have close body
contact
Characterized by lesions on the head, neck and trunk

•
7
...

•
•

Disseminated infecctions
Occur in immunocompromised patients with depressed T
cell function
Examples: Esophagitis and Pneumonia

Causes several disease, both primary and recurrent
o Genital herpes
o Neonatal herpes
o Aseptic meningitis

2
...

•

Aseptic meningitis
usually a mild self-lmited disease with few sequelae

LABORATORY DIAGNOSIS
•
Virus causes cytopathic effect (CPE) in cell culture
•
The virus is identified by antibody neutralization or
fluorescent antibody test

2

EPIDEMIOLOGY
•
HSV-1: Most primary infections in childhood
•
HSV-2: Age of sexual activity

2
...

•
Hsv encephalitis can be diagnosed using a PCR assay to
detect HSV-1 DNA in spinal fluid
TREATMENT
•
Acyclovir is used for the treatment of encephalitis and
disseminated disease [parenteral]
o Can also be useful in treatment of neonatal herpes
infections
o Useful in the treatment of primary and recurrent
genital herpes infections
o Has NO EFFECT on the latent state of the virus
•
Trifluorothymidine: KERATITIS
PREVENTION
•
Primary disease can be prevented by protection from
exposure to vesicular lesions
...

CASE
30 yr old man
•
With frequent episodes of Herpes labialis
•
Asked something about HSV-1
•
What is the most accurate statement?
•
Ans: Main site of latency by HSV-1 is the neurons in the
sensory ganglia of the face
...


PATHOGENESIS
•
Initial infection: OROPHARYNX
•
Then spreads via BLOOD [viremia] into internal organs like
liver
•
Then reach the skin [acute episode]
•
Latent state in sensory ganglia
•
Then reactivate to cause zoster years later [elderly,
immunocompromised]
LABORATORY DIAGNOSIS
•
GOLD STANDARD: cell culture
o The virus cause CPE in cell culture
•
The virus can be identified by fluorescent antibody test
•
Multinucleated giant cells can be seen in smears from the
base of the vesicles
•
A four-fold or greater rise in antibody titer in convalescentphase serum is DIAGNOSTIC
TREATMENT
•
In the immunocompromised patient, acyclovir can prevent
dissemination
•
Both the varicella vaccine and the zoster vaccine contain
live, attenuated VZV
•
Immunocompromised patients exposed to the virus should
receive the following:
o Passive immunization with varicella-zoster
immune globulin [VZIG]
o Acyclovir, as pophylaxis
o Both to prevent disseminated disease
CASE
Regarding VZV, which is most accurate?
•
High dose Acyclovir can eliminate the latent state caused by
VZV
•
The principal site of latency of VZV is in motor neurons
•
Domestic animals are the main reservoir
•
The vaccine against Varicella contains all three serotypes of
formalin-killed VZV as the immunogen
•
When zoster occurs in an immunocompromised patient,
Acyclovir should be given to prevent disseminated
infection
...

•
Zoster is caused by reactivation of latent virus

CYTOMEGALOVIRUS
•
•
•
•
•

Diseases
Transmission
Pathogenesis
Laboratory Diagnosis
Treatment

DISEASES
•
•
•
•

CMV is the most common cause of congenital anomalies
CMV also causes cytomegalic inclusion body disease in
infants
...

o Swollen lymph glands
o Manifestation of TB complex
CMV causes the following in immunocompromised
patients:
o Pneumonia
o Hepatitis
o Retinitis (AIDS patients)
o Enteritis (AIDS patients)

3

Diseases
Transmission
Pathogenesis
Laboratory Diagnosis
Treatment

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•
•
•
•
•

MICROBIOLOGY: DNA ENVELOPED AND NONENVELOPED VIRUSES

TRANSMISSION
•

•

DISEASES

The virus is found in human body
o Blood
o Saliva
o Semen
o Cervical mucus
o Breast milk
o Urine
It is transmitted by these fluids:
o Across the placenta [vertical transmission]
o By organ transplantation

PATHOGENESIS
•
•
•
•
•
•

Initial infection is in the OROPHARYNX
Fetus: infect many organs causing congenital anomalies
like CNS, brain, spinal cord, kidney
Adults: virus goes to the LYMPHOCYTES
Latent: in WBC/leukocytes
Then goes to REACTIVATION
Disseminated infection in immunocompromised patients
can results
o Primary infection
o Reactivation of latent infection

LABORATORY DIAGNOSIS
•
•
•
•

The virus causes CPE in cell culture
...
Gancyclovir supresses retinitis
Do not transfuse CMV antibody positive blood into
newborns or immunocompromised patients

•

•

Epstein-Barr virus causes infectious mononucleosis [IM]
o Erythematous, edematous lymph nodes
o Enlarged LN
o White patches
o Hepatosplenomegaly
o Abdominal pain
o Nausea and vomiting
o Photophobia
o Fever for 2 weeks, chills
o Systemic:
▪
Body malaise
▪
Weakness
Epstein-barr virus is associated with Burkitt’s Lymphoma in
East-African children

TRANSMISSION
•
•

The virus is found in the human oropharynx and B
lymphocytes
Transmitted primarily by saliva
...

CHARATERISTICS
•
Poxviruses are the largest viruses
...

•
DNA-dependent RNA polymerase in virion
...
Accessmedicine
...


TRNSMISSION
•
Respiratory droplets or direct contact with the virus from
skin lesions
...

•
Skin lesions progress in the following order: macule,
papule, vesicle, pustule, crust
...

•
Electron microscopy reveals typical particles; cytoplasmic
inclusions seen in light microscopy
...

•
A four-fold or greater rise in antibody titer in the
convalescent-phase serum is diagnostic
...


•
•
•

People with IM produce antibody that agglutinate sheep
blood cells
The atypical lymphs in the blood of people with IM are EBV
infected T helper cells
Patients with deficient cell-mediated immunity should
receive passive-active immunization against EBV

35-year old man
•
With grand mal seizure this morning
•
MRI: revealed a lesion in the temporal lobe
•
Brain biopsy: multinucleated giant cell with intranuclear
inclusion bodies
•
Which is the most likely cause? Herpes Simplex virus Type
1
•
What is the best choice of drug? Acyclovir
22-year old woman
•
With episodes of bloody diarrhea
•
With CD4 count of 50
•
HIV antibody positive
•
Stool culture for Shigella, Salmonella, and Campylobacter
are negative
•
Assay for Clostridium difficile is negative
•
Colonoscopy revealed ulcerated lesions
•
What virus? CMV
•
Drug? Gancyclovir

PREVENTION
•
Vaccine contains live, attenuated vaccinia virus
...


OTHER HERPESVIRUSES
•
•

Human Herpesvirus 8
Molluscum Contagiosum

HUMAN HERPESVIRUS 8
•
•
•

Causes Kaposi’s Sarcoma in AIDS patients
Lesions are purple in color due to collections of RBCs
The diagnosis is made by pathologic examination of the
lesion

MOLLUSCUM CONTAGIOSUM VIRUS
•
•
•
•
•
•
•

Causes molluscum contagiosum
The lesions are pinkish and popular with an umbilicated
center
Lesions usually occur on the face especially around the
eyes
It is transmitted by DIRECT CONTACT
The diagnosis is made clinically rather than laboratory
means
There is no established antiviral therapy and no vaccine
Cidofovir may be useful in the treatment of extensive
lesions in immunocompromised patients

•
•

Regarding EBV and IM, which one of the following is most
accurate?
EBV enters the latent state primarily in CD4 positive helper
T cells
Approximately 10% of people in the US have been exposed
to EBV

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•

5

CASE

MICROBIOLOGY: DNA ENVELOPED AND NONENVELOPED VIRUSES

ADENOVIRUS
HUMAN PAPILLOMA VIRUS
PARVOVIRUS B19

ADENOVIRUS
•
•
•
•
•
•

Disease
Transmission
Pathogenesis
Laboratory Diagnosis
Treatment
Prevention

DISEASES
•
Adenovirus causes upper and lower respiratory disease
o Pharyngitis
o Pneumonia
•
Enteric strains cause diarrhea
o To cause viral Acute Gastroenteritis
TRANSMISSION
•
Respiratory droplets [primary]
•
Iatrogenic [eye disease]
o Respiratory fluid rub to eyes
•
Fecal-oral [enteric strains
PATHOGENESIS
•
Infects epithelium of [respiratory tract and eyes
•
Then, it causes acute infection
•
This will lead to a persistent, low grade virus production in
pharynx [asymptomatic]
LABORATORY DIAGNOSIS
•
Gold standard: CPE in cell culture
•
The virus can be identified by fluorescent antibody or
complement fixation test
...

•
Alpha interferon is also available as treatment
o Immunocompromised patients
PREVENTION
•
A vaccine containing the capsid proteins of HPV types 6,
11, 16, and 18 is available

PARVOVIRUS B19
•
•
•
•

Disease
Transmission
Pathogenesis
Laboratory Diagnosis

DISEASES
•
Parvovirus causes the slapped cheek syndrome [erythema
infectiosum
•
Also causes:
o Aplastic anmeia
o Arthritis
o Hydrops fetalis
TRANSMISSION
•
Via respiratory droplets or transplacental
PATHOGENESIS
•
Virus infects erythroblasts
•
Leads to aplastic anemia
•
•

Can also form immune complexes
To cause rash and arthritis

•
•

Can also infect the fetus to cause severe anemia
Then it could lead to CHF and edema [hydrops fetalis]

LABORATORY DIAGNOSIS
•
Serologic tests are used for diagnosis

6

•
•
•

PATHOGENESIS
•
Early viral genes [E6 and E&] encode for certain proteins
•
These genes inhibit the activity of proteins encoded by
tumor suppressor genes [p53 and RB]

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DNA NONENVELOPED VIRUSES



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