Herpes, Pox and Adeno are DNA viruses.
Herpes has an icosahedral core surrounded by a lipoprotein envelope. They
contain linear, DS DNA as their genome. The virion does not possess a
polymerase and uses the host cell RNA polymerase to synthesize its viral
They replicate in the nucleus, form intracellular inclusions and are the only
viruses that obtain their envelope by budding from the nuclear membrane.
The virions of Herpes contain a Tegument ( a structure located between the
nucleocapsid and the envelope) which contains regulatory proteins, such as
transcription and translation factors that play a role in viral replication.
Herpes are known to cause Latent Infections, which is the asymptomatic
period after the Acute phase of illness. Reactivation can occur. The latent
period is associated with the synthesis of non-coding regulatory RNA’s
(Latency-associated transcripts /LATS) that suppress replication. Fever, stress,
sunlight etc.. Can trigger off the reactivation of viral replication.
The Herpes family contains six important human pathogens: Herpes simplex
virus types 1 and 2, varicella-zoster virus, Cytomegalovirus(CMV), Epstein Barr
virus (EBV) and Herpesvirus8.
Herpes simplex type 1 and 2 and varicella-zoster cause a vesicular rash, both in
primary infection and subsequent reactivation. CMV and EBV do not.
Herpes simplex type 1 and 2 , Varicella-zoster, and CMV induce the formation
of multinucleated giant cells, observed microscopically by the Tzanck smear.
The Herpes family can be subdivided into 3 categories, based on the cell type
most often infected and the site of latency:
A) The Alpha herpesviruses consisting of Herpes type 1 and 2, varicella-zoster,
infect epithelial cells primarily and cause latent infection in the neurons.
B) The Beta Herpesviruses include the CMV and human herpes6 can infect
and become latent in many tissues.
C) The Gamma Herpesviruses are the EBV and human herpesvirus8, infect
and become latent primarily in lymphoid cells. EBV is also associated with
certain cancers like Burkitts lymphoma and nasopharyngeal carcinoma, and
Herpesvirus8 is with Kaposi’s sarcoma.
Herpes Simplex Type 1 (HSV-1) and Herpes Simplex virus type 2 (HSV-2):
They differ in their antigenicity and the location of lesions caused. HSV-1
lesions are usually above the waist and HSV-2 lesions below the waist.
Acute gingivostomatitis ( in children, fever and vesicular lesions in the mouth.
Primary disease more severe than relapse.
Herpes labialis or cold sores (fever blisters) is milder, recurrent form,
characterized by crops of vesicles usually at the mucocutaneous junction of
lips or nose, recurrences frequently at the same site.
Keratoconjunctivitis or Keratitis, characterized by corneal ulcersand lesions of
the conjunctival epithelium, recurrences can lead to blindness.
Encephalitis, primarily in adults, characterized by a necrotic lesion in one
temporal lobe, with fever, headache, vomitting, seizures and altered mental
status are typical clinical manifestations. HSV-1 encephalitis has a high
mortality rate and cause severe neurologic sequelae in those who survive.
Herpes genitalis, characterized by painful vesicular lesions of
the male/female genitals ant the anal area as well. Lesions more
severe in primary infection than recurrences. Asymptomatic
infections (in urethra/prostae in male and in the cervix in the
female)can occur and the affected individual act as carriers.
Neonatal encephalitis and neonatal herpes. Aseptic meningitis
caused is mild and self-limiting. Neonatal herpes is the
infection of the child at birth due to vesicles within the birth
canal or asymptomatic viral shedding within the birth canal.
The disease varies from severe(disseminated lesions or
encephalitis) to milder local( skin, eye, mouth ) to
asymptomatic infection. The disease likely to be more severe if
the mother is experiencing a primary infection rather than a
recurrent one (more viral load and protective IgG formed in
primary infection cross the placental barrier).
Both HSV-1 and HSV-2 are not known to cause any
significant congenital abnormalities.
Both their infections are associated with Erythema
multiformae ( red-normal skin-red ring ) thought to
be immune-related to the HSV antigens.
HSV-1 transmitted by saliva and HSV-2 by sexual
The virus replicates in the skin or mucous membrane at the
initial site of infection and migrates up the neuron by retrogade
axonal flow and becomes latent in the sensory ganglion cells of
the trigeminal ganglia (HSV-1) or lumbar and sacral ganglia.
During latency, most viral DNA is located in the cytoplasm. On
reactivation by stress, fever hormonal changes, trauma etc.. the
virus migrates down the neuron and replicates in the skin
The typical skin lesion is a vesicle that contains serous fluid
filled with virus particles and cell debris. Multinucleated cells
are typically found at the base of the lesion.
Immunity is incomplete and cell mediated immunity important
to suppress reactivation ,severity and spread of the infection.
HSV binds to heparan sulfate and nectin (receptors on the cell
surface). Viral envelope fuses with the cell membrane and the
nucleocapsid and tegument proteins are released into the
cytoplasm. Viral nucleocapsid docks on to a nuclear pore and
the genome DNA along with tegument protein VP16, enters the
VP16 interacts with cellular transcription factors transcribing
Immediate early (IE) genes by the host cell RNA polymerase.
Translated IE proteins regulate the synthesis of early proteins
such as DNA polymerase that in turn replicates the genome and
late protein synthesis begins .
These late, structural proteins are transported to the nucleus,
where virion assembly occurs. The virus obtains its envelope by
budding through the nuclear membrane.
Isolation of virus from the lesion by growth in the cell culture
where CPE is seen in 1-3 days, after which virus is identified by
fluoroscent antibody staining of the infected cells or by
detecting virus-specific glycoproteins in ELISA.
Rapid diagnosis using the Tzanck smear, where cells from the
base of the vesicles are stained with Giemsa stain, indentifying
presence of multi-nucleates giant cells.
Acyclovir (acycloguanosine) is the treatment of choice.
Avoid contact with the vesicular lesion or ulcer.
Varicella-Zoster virus (VZV ):
Varicella(chickenpox is the primary disease)
Zoster(shingles) is the recurrent form.
Morphologically same but antigenically different from
Virus transmitted by respiratory droplets and by direct
contact with varicella or zoster lesions. Varicella highly
In hospital surroundings, can cause life-threatening
disseminated infections in immunocompromised patients.
Infects the mucosa of the upper respiratory tract then
spreads via blood to the skin where characteristic vesicular
Multinucleated giant cells with intranuclear inclusions
seen in the base of the lesions.
Infects sensory neurons and carried by retrograde axonal
flow into the cells of the Dorsal root ganglia where it
becomes latent. Reactivation causes vesicular skin lesions
and the characteristic nerve pain of the Zoster.
Immunity, life long for varicella, but zoster can occur
Clinical findings after an incubation period of 14-21
days with brief initial symptoms of fever and malaise
followed by vesicular rash on the trunk and spreads to
the head and extremities. The rash evolves from
papules to vesicles, pustules and crusts. Itching is a
prominent symptom. Reye’s syndrome
(encephalopathy and liver degeneration) is associated
with VSV infection.
Zoster infection involves painful vesicles along the
sensory nerve of the head or trunk lasting for weeks
followed by post-zoster neuralgia.
Usually not necessary. Clinical diagnosis is sufficient.
Tzanck smear and observing multinucleated cells and for
definitive diagnosis by isolating virus in cell culture and specific
No treatment required. Acyclovir for immunocompromised
individuals or disseminated disease.
Prevention includes vaccine for varicella (children from 1-12
years) and vaccine for Zoster (adults above 60 who have had
varicella) . Both contain live, attenuated VZV. Zoster vaccine
contains many (14) times more VZV than varicella vaccine. Not
to be given to immunocompromised individuals.
Varicella-zoster immune globulin also available for prophylaxis.
Most common cause of congenital abnormalities
(cytomegalic inclusion disease) in neonates.
Important cause of viral pneumonia in the
Antigenically different from other members of the Herpes
family. As giant cells are formed, known as cytomegalo.
Mode of transmission is varied from across the placenta,
within the birth canal, and breast milk.
In young children spreads through saliva and sexually in
adults (present in semen and cervical secretions), during
blood transfusion and organ transplant..
Infection of the fetus can cause cytomegalic inclusion
disease, characterized by multinucleated giant cells with
prominent intranuclear inclusions. Congenital
abnormalities more common when fetus infected during
the first trimester.
CMV enters latency in the monocytes reactivated ( in
cervical cells resulting in infection of newborn) when cellmediated immunity is reduced and can persist in kidneys
As the assembly of the MHC-I complex is unstable in CMV
infected cells, viral antigens are not displayed properly and
can evade action by the cytotoxic T-cells. Thus, CMV can
cause an immunosuppressive effect by inhibiting T-cells.
Clinical findings of Cytomegalic inclusion disease
include microcephaly, seizures, jaundice, deafness
with hepatosplenomegaly and mental retardation in
Systemic CMV infections like pneumonitis and
hepatitis in immunocompromised cases.
Same as isolate virus in cell culture with fluoroscent
Fluoroscent antibody and histologic staining of inclusion
bodies in giant cells appear as oval owl’s eye shaped.
Pp65 is a nucleocapsid protein of CMV, identified within
infected leukocytes using fluoroscein labelled monoclonal
Treatment : Ganciclovir (cytovene) effective.
Prevention: No vaccine. Blood and all pre disposing factors
to be screened for CMV.
Epstein-Barr virus (EBV):
EBV causes Infectious mononucleosis. Associated with Burkitts
Lymphoma, naso-pharyngeal carcinoma, other B-cell
lymphomas and Hairy leukoplakia. It can also infect the
epithelial cells of the pharynx and cause a severe sore throat.
EBV antigenically different. Most important diagnostic antigen
is the Viral Capsid antigen(VCA).
EBV mainly infects the lymphoid cells, primarily Blymphocytes. In latent stage, its genome is in the nucleus, not
integrated into the cellular DNA.
Mode of transmission through saliva (kissing) . Blood
transmission is rare.
Infection occurs in the oropharynx and spreads to the
blood where it infects the B-lymphocytes. Cytotoxic Tcells react against the infected B-cells and these Atypical
lymphs are seen in the blood smear.
IgM antibodies as the first line of immune response is
diagnostic of acute infection.
Non-specific heterophil antibodies are found. Heterophil,
because they are detected by different antigens from the
ones that induced them. These heterophil antibodies can
agglutinate sheep and horse RBC’s in the lab.
Infectious mononucleosis characterized by fever, sore throat,
lymphadenopathy and splenomegaly with hepatitis and encephalitis
in some patients.
Can cause a severe fatal progressive form of Infectious mononucleosis
in children with X-linked lymphoproliferative syndrome, a inherited
immunodeficiency of the mutated gene coding for a signal
transcduction protein required for both T-cell and NK-cell function.
Hairy leukoplakia manifests as a whitish, lesion with hairy surface on
the lateral side of the tongue, especially in immunocompromised HIV
EBV associated with Burkitt’s lymphoma and other malignancies.
EBV associated post-transplant lymphoproliferative disorder(PTLD)
manifesting as a B-cell lymphoma, following bone-marrow and solid
organ transplants due to their immunosuppressed condition.
Hematological approach reveals absolute Lymphocytosis
with about 30% of them abnormal. These are the atypical
lymph which appear as large with an expanded nucleus,
and an abundantly vacuolated cytoplasm. These are the
cytotoxic T-cells that react with the infected B-cells.
The heterophil antibody titer useful for prior detection (as
antibody titers decline on recovery).
EBV specific antibody tests to diagnose difficult cases. IgM
VCA antibody response for early diagnosis.
No isolation of the virus done as it is very difficult.
Treatment : No antiviral required. High doses of
Acyclovir for life threatening EBV infections.
Human Herpesvirus 8 (HHV-8):
Associated with Kaposi’s sarcoma mespecially in
Malignant transformation is by inactivation of the
RB(retinoblastoma) tumor suppressor gene.
KS is a malignancy of vascular endothelial cells that
contains many spindle shaped cells and erythrocytes. The
lesions are dark purple, flat to nodular and appear at
multiple sites such as skin, oral cavity and soles. Internally
lesions occur in the GI tract.
No specific antiviral therapy and no vaccine against
The poxvirus family includes smallpox virus, vaccinia virus
and molluscum contagiosum virus (MCV).
Poxviruses are the largest and most complex viruses.
They are brick shaped , DS-DNA, a disc shaped core with a
double membrane and a lipoprotein envelope. The virion
contains a DNA-dependent RNA polymerase, as it
replicates in the cytoplasm with no access to cellular RNA
Single serotype and infects only humans.
Replication cycle entirely in the cytoplasm, unusual for a
Small pox virus:
Also called Variola virus.
Transmitted by respiratory aerosolor by direct contact
either in the skin lesions or on fomites such as bedding.
Virus infects the upper respiratory tract and local lymph
nodes and enters the blood stream (primary viremia).
Internal organs infected and the virus reenters the blood
(secondary viremia)and spreads to the skin. The rash is
the result of the virus replication in the skin followed by
cytotoxic T-cells attacking virus-infected cells.
Incubation of 7-14 days with a sudden onset of fever
and malaise, followed by rashes, worse on the face
and extremities than on the trunk. The rash evolves
from macules to papules, vesicles, pustules and finally
crusts in 2-3 weeks.
By growing the virus in cell culture or chick embryo.
Also by detecting viral antigens in vesicular fluid by
By vaccine containing live attenuated vaccinia virus is
Molluscum contagiosum virus (MCV) :
Distinct from small poox and vaccinia virus.
The lesion is flesh colored on the skin, painless
nonpuritic and not inflammed with a charcteristic
cup-shaped crater with a white core.The lesion
consists of hyperplastic epithelial cells with a
cytoplasmic inclusion body containing MCV progeny.
MCV transmitted by close contact, and common in
children and immunocompromised individuals.
Treatment is to boost cell-mediated immunity.
Adenoviruses are icosahedral, non-enveloped, with DS-
It is the only virus with fiber (organ of attachment and is a
hemagglutinin) protruding from each of the 12 vertices of
the capsid. The fiber, purified free from the virions is toxic
to human cells.
They cause a variety of upper and lower respiratory
disease like pharyngitis, conjunctivitis (pink eye), common
cold and pneumonia.
Keratoconjunctivitis, hemorrhagic cystitis and
gastroenteritis can also occur.
Virus assembly occurs in the nucleus and released by cell
lysis and not by budding.
Transmitted through aerosol droplet, feco-oral route 9most
common among children) and direct innoculation of
conjunctiva with fingers.
41 antigenic types known based on their type specific fiber
These infect the mucosal epithelium of several organs like the
respiratory tract, the GI tract and the conjunctivas. Immunity
based on type specific neutralizing antibody and is life long.
Acute infection leads to cell death with the latent infection
particularly in the adenoidal and tonsillar tissues of the throat.
Clinical findings include fever, sore throat, runny
nose and conjunctivitis. Lower respiratory tract
involvement is associated with bronchitis and atypical
Hematuria and dysuria prominent in hemorrhagic
Gastroenteritis with non-bloody diarrhea in children
below 2 years.
Involves isolation of virus in cell culture.
Complement fixation tests and Hemagglutination
inhibition tests are diagnostic.
No antiviral therapy.
Prevention by hygiene. No vaccine for civilian use.