Herpesviridae

Enveleoped, icosahedral capsid, ds linear DNA, replicate in the nucleus.

Classified into 3 subclasses:
Alpha, Beta and Gamma.

Between the envelope and the capsid lies a proteinaceous material called tegument,
which contains virus-encoded enzymes and transcription factors essential for initiation
of the infectious cycle, although none of these is a polymerase.

Alphaherpesvirinae

Herpes simplex 1
Herpes simplex 2
Varicella-zoster virus
All herpes viruses have the ability to enter a latent state (in the ganglia) following
primary infection of their natural host and be reactivated at a later time.

HERPES SIMPLEX VIRUS TYPES 1 AND 2

HSV-1 and HSV-2 are the only human herpesviruses with substantial nucleotide
sequence identity (about 50%). Therefore, they share many common features in:

Replication
Disease production
Latency.

Transmission of both HSV types is by direct contact with virus containing secretions or
with lesions on mucosal or cutaneous surfaces.

Clinical significance

Although HSV-1 is often found in oral or ocular lesions (above the waist), and HSV-2 is
commonly the cause of genital lesions (below the waist), HSV-1 can infect the genital
tract, causing similar lesions, and HSV-2 can cause lesions in the oral cavity.

Many primary HSV infections are subclinical, but the most common symptomatic
infections of the upper body are gingivostomatitis in young children
and pharyngitis or tonsillitis in adults. The painful lesions typically consist of vesicles
and shallow ulcers, which are often accompanied by systemic symptoms, such as
fever, malaise, and myalgia.
If HSV infection spreads to the central nervous system (CNS), it can cause
encephalitis, which, if untreated, has a mortality rate estimated to be 70%. Survivors
are usually left with neurologic deficits
Primary genital tract lesions are similar to those of the oropharynx.
The majority of these infections are asymptomatic.
When symptomatic (genital herpes), local symptoms include:
painful vesiculoulcerative lesions on the vulva, cervix, vagina, and perianal area
in women and the penis or anus in men.
Systemic symptoms of fever, malaise, and myalgia may be more severe than those
that accompany primary oral cavity infections.

In pregnant women with a primary genital HSV infection, the risk of infecting the
newborn during birth (neonatal herpes) is estimated to be 30%-40%.
Because neonates have no protective maternal antibody, a disseminated infection,
often involving the CNS, may result.
Untreated neonatal herpes has a high mortality rate, and survivors are likely to have
permanent neurologic sequelae.

Reactivation:

Several factors induce reactivation and replication of the virus:

-Hormonal changes
-Fever
-Physical damage to latently infected neurons

Herpes simplex virus type 1:

The frequency of oropharyngeal symptomatic recurrences is variable, ranging from

none to several per a year.
The lesions occur as clusters of vesicles at the border of the lips (herpes labialis or
"cold sores" or "fever blisters") and heal without scarring in 8-10 days.

Herpes simplex virus type 2:

Reactivation of HSV-2 genital infections can occur with greater frequency (monthly)
and is often asymptomatic but still results in viral shedding.

Consequently, sexual partners or newborn infants may be at increased risk of

infection in the absence of precautions against transmission.

The risk of transmission to the newborn is much less than in a primary maternal
infection because less virus is shed and the baby has some maternal anti-HSV
antibody, which may also lessen the severity of disease if transmission does occur.
Laboratory identification

Identification is important to prevent neonatal infection and HSV encephalitis.

There are a variety of tests available for the detection of HSV including:
-Viral culture
-Immunofluorescence or immunoperoxidase staining with antibodies directed against
viral early proteins.
-Direct detection of viral DNA by hybridization techniques.
-PCR

In patients with encephalitis, HSV etiology can be confirmed by demonstration of viral

DNA in the cerebral spinal fluid (CSF) instead of brain biopsy.

Treatment

The guanine analog, acycloguanosine (acyclovir), is selectively effective against HSV

because it becomes an active inhibitor of DNA synthesis only after phosphorylation by
the HSV thymidine kinase.

Other drugs effective in treating herpes simplex infection include famciclovir

and topical penciclovir, which is active against HSV-1, HSV-2, and VZV.

None of these drugs can cure a latent infection, and they can reduce, but not eliminate,
asymptomatic viral shedding and recurrences of symptoms.

VARICELLA-ZOSTER VIRUS

Biological similarities between VZV and HSV include:

-Rapidly cytolytic infections

-Latency in sensory ganglia.

Primary infections with VZV cause varicella ("chickenpox"), whereas reactivation of

the latent virus causes herpes zoster ("shingles").

Epidemiology and pathogenesis

VZV is the only herpesvirus that can be easily spread from person to person by casual
contact.
Transmission of VZV is usually via respiratory droplets and results in initial infection of
the respiratory mucosa, followed by spread to regional lymph nodes.
Progeny viruses enter the bloodstream, undergo a second round of replication in cells
of the liver and spleen, and are disseminated throughout the body by infected
mononuclear leukocytes.
Endothelial cells of the capillaries and, ultimately, skin epithelial cells become
infected, resulting in the characteristic, virus-containing vesicles of chickenpox that
appear from 14 to 21 days after exposure.
The infected individual is contagious, 1 to 2 days before the appearance of the
exanthema.
The vesicular fluid from the chickenpox rash is also highly contagious.

Clinical significance

Neither chickenpox nor shingle is usually life threatening in the normal, healthy
individual, but both can have severe complications in immunocompromised patients.

Primary infection (varicella or chickenpox):

The incubation period is most commonly from 14 to 16 days. The first appearance of
exanthem is often preceded by1-2 days of a prodrome of fever, malaise, headache,
and abdominal pain.

The exanthem begins on the scalp, face, or trunk as erythematous macules, which
evolve into virus-containing vesicles that begin to crust over after about 48 hours.
Itching is most severe during the early stage of vesicle development.

In older adults and the immunocompromised, lesions may also appear on mucous
membranes, such as in the oropharynx, conjunctivas, and vagina.
Varicella is a more serious disease in adults than it is in children.
Varicella pneumonia is the most common of the serious complications, but
fulminant hepatic failure and varicella encephalitis may also result.

Primary infection of a pregnant woman may cause her to contract the more severe
adult form of varicella and may affect the fetus or neonate as well.
Fetal infection early in pregnancy is uncommon but can result in multiple
developmental anomalies.

Reactivation (herpes zoster or shingles):

Latency is established in sensory ganglia.

Herpes zoster results from reactivation of the latent virus rather than from new,
exogenous exposure.
Reactivation occurs in up to 30% of individuals who have been infected at some point
during their lifetime.
Even after the lesions heal, some individuals continue to suffer debilitating pain for
months to years. This postherpetic neuralgia (PHN) is the most significant
sequela of herpes zoster.
Laboratory identification

Rapid diagnosis can be made using PCR to detect virus DNA in tissues, vesicular
fluid, maculopapular lesions, or crusts from lesions.
VZV can also be detected by immunofluorescence or immunoperoxidase staining with
antibodies against viral early proteins or by in situ hybridization with-specific DNA
probes.
Viral culture can also be performed.

Treatment

Acyclovir has been the drug of choice, but requires intravenous administration to
achieve effective serum levels.
Early administration of oral acyclovir reduces the time course and acute pain of zoster.
Famciclovir and valacyclovir can also be used.

Prevention

Certain susceptible individuals (eg, neonates born to mothers with active chickenpox
and severely immunocompromised patients) can be protected by administration
of varicella-zoster immunoglobulin (VariZIG).
A live, attenuated vaccine for children age 1 year or older is now recommended.

RNA viruses

Paramyxoviruses

Single Negative strand, Helical, Enveloped

Mumps virus:

Mumps used to be one of the commonly acquired childhood infections.

Adults who escape the disease in childhood could also be infected.
The virus spreads by respiratory droplets. Although about one-third of infections are
subclinical, the classic clinical presentation and diagnosis focus on infection and
swelling of the salivary glands, primarily the parotid glands. However, infection is
widespread in the body and may involve not only the salivary glands but also the
pancreas, CNS, and testes. Orchitis (inflammation of the testis) caused by mumps
virus may cause sterility.

A live, attenuated vaccine (MMR for measles, mumps and rubella).

[Note: Individuals who have had the disease develop lifelong immunity].
Measles virus

Viral replication:

The cellular receptor for measles virus is the CD46 molecule, a protein whose normal
function is to bind certain components of complement. Although the viral attachment
protein has hemagglutinating activity, it lacks neuraminidase activity. Hence, it is
referred to as the H protein, rather than HN protein. An F protein facilitates uptake of
the virion.
Measles virus replication in tissue culture and certain organs of the intact organism is
characterized by the formation of giant multi nucleate cells (syncytia formation),
resulting from the action of the viral spike F protein.

Pathology:

Measles virus is transmitted by sneeze- or cough-produced respiratory droplets.

The virus is extremely infectious, and almost all infected individuals develop a
clinical illness.
Measles virus replicates initially in the respiratory epithelium and then in various
lymphoid organs. Classically, measles (also referred to as rubeola) begins with a
prodromal period of fever, cough, coryza (runny nose), and conjunctivitis (often
referred to as the "3 Cs").
Two to 3 days later, specific diagnostic signs develop. First, Koplik spots (small white
spots on bright red mucous membranes of the mouth and throat) appear, followed by a
generalized macular rash, beginning at the head and traveling slowly to the lower
extremities. Soon after the rash appears, the patient is no longer infectious.

The major morbidity and mortality caused by measles are associated with various
complications of infection, especially those affecting the lower respiratory tract and
the CNS. The most important of these is postinfectious encephalomyelitis,
which is estimated to affect 1 of 1,000 cases of measles, usually occurring within 2
weeks after the onset of the rash.
Children are particularly susceptible, especially those weakened by other diseases
or malnutrition. Measles is, therefore, an important cause of childhood mortality in
developing countries.

Diagnosis:
The presence of Koplik spots provides a definitive diagnosis.
Laboratory diagnosis is made by demonstrating an increase in the titer of antiviral
antibodies.

Prevention:
Measles is usually a disease of childhood and is followed by lifelong immunity.
A live, attenuated measles vaccine is available in routine immunization.
Also, MMR is widely used.