HERPES VIRUSES

By:

Prof. MS Odimayo MB;BS, PGDE, FMCPath

Consultant, Microbial Pathologist/Laboratory Physician

Department of Microbial Pathology,

Faculty of Basic Clinical Sciences,
UNIMED, Ondo City,
Nigeria
 INTRODUCTION
• The name herpes comes from the Latin herpes
(Greek word herpein) meanings to creep. This
reflects the creeping or spreading nature of the
skin lesions caused by many herpesviruses
• Herpes viruses are a leading cause of human
viral disease, second only to influenza and cold
viruses.
• They are characterised by active and latent
diseases e.g Chickenpox/shingles.
• Once infected is for life!
 VIROLOGY
• Envelope: Herpes viruses are enveloped
viruses. Envelope is acquired during budding
from nuclear membrane.
• Tegument: Between the envelope and the
capsid is the tegument which contains virally-
encoded proteins and enzymes involved in the
initiation of replication
• Capsid: They are doughnut shaped with
icosahedral nucleocapsid.
 VIROLOGY Ctd
• Genome: they posses double stranded DNA.
The size of the genomes differs with
cytomegalovirus having the largest genome
• Outstanding characteristics include:
Establishment of latent infections, indefinite
Persistence in infected hosts, Frequent
reactivation in immunosuppressed hosts,
• Some are cancer-causing: e.g Epstein Barr
virus ( Burkitt’s lymphoma), HHV-8 (kaposi)
 CLASSIFICATIONS
• classified into 3- subfamilies; α(3), β(3), γ(2)
1. Alphaherpesviruses are fast-growing, cytolytic
viruses that tend to establish latent infections in
neurons. Human herpes simplex virus-1 (HHSV-1),
HHSV-2, & varicella zoster virus.
2. Betaherpesviruses are slow-growing and may be
cytomegalic (massive enlargements of infected cells)
and become latent in secretory glands and kidneys
e.g Cytomegalovirus, human herpesviruses 6 and 7.
3. Gammaherpesviruses infect and become latent in
lymphoid cells. e.g Epstein Bar Virus (EBV), & HHSV-
8 (kaposi sarcoma-associated herpes virus).
 CLASSIFICATIONS Ctd
• 1. Herpes simplex virus Type 1 (HSV-1)- α
• 2. Herpes simplex virus Type 2 (HSV-2)- α
• 3. Varicella Zoster Virus (VZV)-α
• 4. Cytomegalovirus (CMV)- β
• 6. Human herpes virus 6 (exanthum subitum
or roseola infantum)- β
• 7. Human herpes virus 7- β
• 4. Epstein Barr virus (EBV)- ᴕ
• 8. Human herpes virus 8 (Kaposi's sarcoma-
associate herpes virus) -ᴕ
 REPLICATION
• The virus enters the cell by fusion with the cell
membrane after binding to specific cellular receptors
e.g heparan sulfate via envelope glycoproteins.
• After fusion, the capsid enters the nucleus where
uncoating occurs; the DNA becomes associated with
the nucleus.
• Expression of the viral genome is tightly regulated
and sequentially ordered in a cascade fashion.
• Expression of Immediate-early genes yields "alpha"
proteins which are translated into "beta" proteins,
then viral ‘DNA’ replication and production of late
transcripts ("gamma" proteins).
 REPLICATION Ctd
• α and β proteins are mainly enzymes or DNA-
binding proteins; while γ are structural proteins.
• Maturation occurs by budding of through nuclear
membrane. Enveloped virus particles are
transported by vesicular movement to cell surface.
• Cells productively infected are invariably killed.
Host molecular synthesis is shut off early in
infection
• Cellular DNA and protein synthesis virtually stop as
viral replication begins.
 PATHOGENESIS & PATHOLOGY
• HSV is transmitted by contact with an
individual excreting the virus or droplets via
mucosal surfaces or broken skin.
• HSV-1 infections are usually limited to the
oropharynx while HSV-2 is by genital routes.
• Viral replication occurs first at the site of
infection, invades local nerve endings, then
transported by retrograde axonal flow to
dorsal root ganglia, where, after further
replication, latency is established.
 PATHOGENESIS & PATHOLOGY
• Because HSV causes cytolytic infections,
pathologic changes are due to necrosis of
infected cells and inflammatory response.
• Lesions induced in the skin and mucous
membranes by HSV-1 and HSV-2 resemble
those of varicella-zoster virus.
• Changes induced by HSV are similar for
primary and recurrent infections but vary in
degree, reflecting the extent of viral
cytopathology.
 MANIFESTATIONS
• Primary HSV infections may be asymptomatic.
• Rarely, systemic disease develops, involving
multiple organs in immunocompromised host.
• Latent infections: occurs in nonreplicating
state (Oropharyngeal HSV-1 in trigeminal
ganglia; genital HSV-2 in sacral ganglia).
• Provocative stimuli e.g fever, emotional stress
e.t.c can reactivate virus from the latent state,
manifest as cold sores (fever blisters) near the
lip in more over 80% of humans
 Herpes Virus and Common Diseases
• HSV-1 at the lip or mouth “cold sores”; HSV-2 can also be responsible
• HSV-2 genital herpes; HSV -1 can also be responsible

HSV-1 Cold sore HSV-2 Genital Herpes

CLINICAL MANIFESTATIONS Ctd
• Keratoconjunctivitis of HSV-1 infections may
occur in the eye, causing keratoconjunctivitis.
• Oropharyngeal disease: Involves buccal and
gingival mucosa of the mouth in children of 1-
5 years. Symptoms include fever, sore throat,
vesicular and ulcerative lesions, gingivitis.
• Pharyngitis and tonsillitis may occur in adult
• Neonatal Herpes: HSV infection of the
newborn may be acquired in utero, during
birth, or after birth. may be very severe.
 CLINICAL MANIFESTATIONS CTD
• Chickenpox (varicella): caused by Varicella-zoster virus
on primary infection and zoster (shingles) on reactivation
of latent infection.
• Infectious mononucleosis: caused by Epstein-Barr virus
follwing replication in epithelial cells of the oropharynx
and parotid gland and establishes latent infections in
lymphocytes.
• Cytomegalic inclusion disease may occur In newborns,
CMV is an important cause of congenital defects and
mental retardation.
• Exanthem subitum (roseola infantum): caused by human
herpesvirus 6 following T lymphocytes infection.
 HSV Establishes Latent Infections
• Once infection has taken place HSV can remain dormant
for months, years, lifetime
• Examples:
– Shingles which can appear years after first chickepox infection
(caused by varicella zoster, causes both chickenpox and shingles)
CLINICAL MANIFESTATIONS CTD
• Human herpesvirus 7, also a T-lymphotropic
virus, has not yet been linked to any specific
disease.
• Malignancy: Epstein-Barr virus (Burkitt's
lymphoma, nasopharyngeal carcinoma, and
other lymphomas); Human herpesvirus 8 or
Kaposi's sarcoma-associated herpesvirus
(Kaposi's sarcoma).
• Encephalitis: severe encephalitis may be
caused especially by HSV-1 with a high
 LABORATORY DIAGNOSIS
• Cytopathology: staining of scrapings obtained
from the base of a vesicle (eg, with Giemsa's
stain); the presence of multinucleated giant cells
indicates that herpesvirus (HSV-1, HSV-2, or
varicella-zoster) is present,
• Virus isolation: during primary infection and
during asymptomatic periods. Therefore, the
isolation of HSV is not in itself sufficient
evidence to indicate that the virus is the
causative agent of a disease under investigation.
 LABORATORY DIAGNOSIS Ctd
• Polymerase Chain Reaction (PCR)
• Serology: Antibodies appear in 4–7 days after
infection and reach a peak in 2–4 weeks. They
persist with minor fluctuations for the life of
the host. The use of HSV type-specific
antibodies, available in some research
laboratories, allows more meaningful
serologic tests.
 TREATMENT AND PREVENTION
• Antiviral drugs including acyclovir, valacyclovir, and
vidarabine. Acyclovir is currently the standard
therapy. All are inhibitors of viral DNA synthesis.
• The drugs may suppress clinical manifestations,
shorten time to healing, and reduce recurrences of
genital herpes. However, HSV remains latent in
sensory ganglia.
• Newborns and persons with eczema should be
protected from exposure to persons with active
herpetic lesions.
• Experimental vaccines of various types are being
developed.
• Thank you