HERPESVIRUS - Adulthood: 70-90% have type 1 ab
• Encode many enzymes
• Establish latent infections
• Persists indefinitely in infected hosts  • 40-60 M infected in US
• Frequently reactivated
immunosuppressed hosts
• Some cause cancer
Properties:
• Virion: Spherical, 150-200 nm in diameter
(icosahedral)
• Genome: Double-stranded DNA, linear,
125-240 kbp, reiterated sequences
• Proteins: <35 in virion
• Envelope: viral glycoproteins, Fc receptors
• Replication: nucleus, bud from nuclear
membrane  (rare:disseminated infection after primary
Classification:
Epidemiology:
HSV infection
• Human viruses are not associated with
animal reservoir or vectors:
- Symptomatic or asymptomatic
infections can be reservoir for
transmission; HSV 1 and 2 can be
reactivated
HSV 1 infection
• MOT: contact with secretions (saliva) or
fomites contaminated with saliva of a
virus- shedding person
• Symptomatic adults with herpetic lesions
or shedding asymptomatic adults are the
ones who usually infect the children
• Primary infection
• Asymptomatic: leads to carrier state for a
lifetime. However, there may be a
transient recurrent attack of herpes
• Antibodies:
HSV 2 infection
in • MOT: sexually transmitted
• Abs:
- No abs before puberty; cross-
reactivity with type 1 and 2 abs
• Results with HSV 2
- 17% adults with HSM 2 Ab; 30-49 yrs
old
- Higher in woman; higher in blacks
Maternal HSV
• Can endanger the mother and fetus
infection in mother)
- Fetus acquire virus by birth canal
shedding during delivery
- Spontaneous abortion- HSV
1(primary) before 20 weeks of
gestation
Genital HSV
• Can increase chances of acquiring HIV due
to ulcerative lesions or opening in mucosa.
Pathogenesis:
• Changes are due to the necrosis of infected
cells together with the inflammatory
response.
• Lesions induced in the skin and mucous
membranes are the same and resemble
those of the varicellazoster virus.
• Changes are similar for primary and
recurrent infections but vary in degree,
reflecting the extent of viral cytopathology.
• Cell fusion: efficient method for cell-to-cell
spread of HSV, even in the presence of
neutralizing antibody.
• HSV entry is initiated by fusion of the viral
envelope.
• During viral assembly, immature,
enveloped HSV particles fuse with the
outer nuclear membrane in a process
termed de-envelopment.
• Viral infection induces syncytium formation
(fusion of infected cells with neighboring
 cells) leading to the formation of - Contact of a susceptible person with
multinucleated enlarged cells. an individual excreting virus.
• Histopathology changes include: - Virus must encounter mucosal surfaces
- Ballooning of infected cells or broken skin
- Primary HSV infections: mild;
asymptomatic o Widespread organ
involvement: immunocompromised
host is not able to limit viral replication
and viremia ensues.
- HSV-1
▪ Limited to the oropharynx
▪ Respiratory droplets or by
- Cowdry type A intranuclear inclusion direct contact with infected saliva
bodies - HSV-2
▪ MOT: genital routes
• Latent infection
- Viral persistence lasts for the lifetime
of the host; very few viral genes are
expresses
- Spontaneous reactivations occur
despite HSV specific humoral and
cellular immunity in the host
▪ Recurrent infections are less
extensive and less severe
▪ Symptomatic: cold sores near
the lip
Clinical Manifestations and Complications:
Oropharyngeal Disease

• Primary HSV-1 infection:

- Margination of chromatin
- Formation of multinucleated giant cells
Asymptomatic
• Symptomatic disease: in small children
(1-5 years of age involves the buccal
and gingival mucosa of the mouth)
• 3-5 days incubation period: 2-3 weeks
clinical illness
• Symptoms: fever, sore throat, vesicular
and ulcerative lesions,
gingivostomatitis and malaise
• Gingivitis is the most striking and
common lesion
• Recurrent: cluster of vesicles most
commonly localized at the border of
the lip.
• Recurrences: asymptomatic and of
short duration (24 hours)

Keratoconjunchivitis

• Primary Infection • HSV-1 infections may occur in the eye

 • Recurrent: eyes are common and
appear as dendritic keratitis or corneal
ulcers or as vesicles on the eyelids
Genital Herpes
• Usually caused by HSV-2
• Primary infections: severe, with illness
Neonatal Herpes
lasting about 3 weeks
• Characterized by vesiculoulcerative
lesions of:
- the penis of the male
- cervix, vuva, vagina, and
perineum of the female
• lesions: very painfult associated with
fever, maaise, dysuria,
lymphadenopathy
• Viral excretion: about 3 weeks
• Cross-reactivity: provides protection
against heterotypic infection
• Recurrences: common; mild
• Virus is shed for only a few days
- Recurences: asymptomatic with
anogenital shedding lasting less
than 24 hours
• Symptomatic or asymptomatic: a person
shedding virus can transmit the infection
to sexual partners
Skin Infections
• Intact skin is resistant to HSV; localized
lesions by HSV-1 or HSV-2: occur in
abrasions that become contaminated
with the virus (traumatic herpes)
Infections in Immunocompromised Hosts
- Fingers of dentists and hospital
personnel (herpetic whitlow)
- Bodies of wrestlers (herpes
gladiatorum or mat herpes)
• Cutaneous infections: severe and life-
threateniing in individuals with disorders
of the skin
• Eczema herpeticum: is a primary
infection in a person with chronic
eczema
Encephalitis
• HSV-1 infections: cause of sporadic, fatal
encephalitis in the US
• Carries a high mortality rate
- Survivors: residual neurologic
defects
• About half of patients: have primary
infections, and the rest have recurrent
infection
• acquired in utero, during birth, or after
birth
- mother: most common source of
infection in all cases
• Contact with herpetic lesions in the birth
canal: most common route of infection
- recommended: delivery by
caesarean section
• Neonatal herpes: acquired postnatal by
exposure to either HSV-1 or HSV-2
• Sources of infection: family or hospital
personnel who are shedding virus
• Babies with neonatal herpes exhibit
three categories of disease
- lesions localized to the skin, eye,
and mouth;
- encephalitis with or without
localized skin involvement; and
- Disseminated disease involving
multiple organs, including the
central nervous system
• viral pneumonitis or intravascular
coagulopathy- cause of death of babies
with disseminated disease
• at increased risk of developing severe
HSV infections
- patients immunosuppressed by
disease or therapy: individuals
with malnutrition
• at particular risk for severe herpes
infections
- Renal, cardiac, and bone marrow
transplant recipients
• more frequent and more severe HSV
intections
- Patients with hematologic
malignancies: patients with AIDS
 • prone to fatal disseminated HSV - Must be consoled that shedding is
infections frequently encouraged with use
- Mainourished chilcren antiviral therapy and condoms
• Vaccines are being developed
Methods of Diagnosis:
- Primary Infection vaccine:
CYTOPATHOLOGY Recombination experiment with
• Rapid cytologic method purified glycoprotein antigens from
• stain scrapings viral envelope
• the presence of multinucleated giant cells
• distinguishing lesions
ISOLATION AND IDENTIFICATION OF
VIRUS
• Virus isolation: definitive
diagnostic approach.
• Isolation of HSV: not in itself
sufficient evidence to indicate
that the virus is the causative
agent of disease under
investigation
• Inoculation of tissue cultures:
used for viral isolation
- agent is identified by Nt test
or immunofluorescence
staining with specific
antiserum
• Typing of HSV isolate: done using
monoclonal antibody or by
restriction endonuclease analysis
of viral DNA
POLYMERASE CHAIN REACTION (PCR)
• Used to detect virus and are sensitive and
specific.
• PCR amplification from CSF: replaced viral
isolation from brain tissue obtained by
biopsy or at post-mortem examination as
the standard assay for specific diagnosis of
HSV infections of the central nervous
system
SEROLOGY
• Antibodies: appear in 4–7 days after
infection and reach a peak in 2–4 weeks
• The use of HSV type-specific antibodies:
allows more meaningful serologic tests.

Prevention and Control:

• New-borns and persons with eczema must

avoid persons with herpetic lesions
• Patients with genital herpes.