HERPESVIRUS

Titiek Djannatun
Bagian Mikrobiologi FK Universitas YARSI
 PENDAHULUAN

Insiden meningkat  Inggris, Wales, Ireland, USA

(1995-2000)  Seluruh dunia:
Bertambah padat populasi
manusia Bertambah mobilitas
manusia
Kemajuan teknologi  Mengubah perilaku sex
Tidak adanya vaksin untuk sebagian besar
STD
 Herpes simpleks dan HIV tersedia
Kondom  melindungi
Orang yang tidak disirkumsisi  Resiko
tinggi Infeksi Gonorrhoea  Mudah
 VIRUS PENYEBAB STD
ORGANISME PENYAKIT KETERANGAN TERAPI

PAPILLOMAVIRUS Genital Warts, Paling sering  Kanker Podophylin, Cryotherapy

(Tipe Dysplasia servix, Kanker penis, dll
6 & 11  Genital Warts)

Herpes Simplex virus Genital Herpes Meningkat  Masalah Aciclovir,

tipe 1 dan 2 laten dan reaktivasi valaciclovir,
Famciclovir

HIV AIDS Insiden meningkat di Nukleosida, Nukleotida, Non-

seluruh dunia Nucleoside reverse
transcriptase inhibitors, Fusi
inhibitors, Protease inhibitors

Virus Hepatitis B Hepatitis 300 Juta carrier di seluruh Lamivudin, Adefovir, IFN α
dunia
Congenital, Perinatal, and Neonatal Viral
Infections
Intrauterine Viral Infections Perinatal and Neonatal
Infections
Rubella Human Herpes Simplex
Cytomegalovirus (CMV) VZV
Parvovirus B19 Cytomegalovirus (CMV
Varicella-Zoster (VZV) Enteroviruses
Enteroviruses HIV
HIV Hepatitis B
HTLV-1 Hepatitis C
Hepatitis C HTLV-1
Hepatitis B
Lassa Fever
Japanese
Encephaliti
 STRATEGI VIRUS MELAWAN
PERTAHANAN HOSPES
PERTAHANA STRATEGI CONTOH
N HOSPES VIRUS

Urine flow (untuk infeksi Infeksi sel epitel atau sub Herpes Simplex virus
uretra) epitel uretra

Inflamasi Merangsang respon inflamasi Herpes Simplex virus

kuat

Cell Mediated Immune Variasi antigenik, Papillomavirus

Response (Sel T, disertai reinfeksi
Limfokin, Sel NK, dll) Variasi antigenik HIV
diantara individu
Faktor yang tidak diketahui HIV
 Sebabkan respon CMI
tidak egektif F
 Properties of herpesviruses
 Enveloped double stranded DNA viruses.
 Genome consisits of long and short fragments which may be
orientated in either direction, giving a total of 4 isomers.
 Three subfamilies:
– Alphaherpesviruses - HSV-1, HSV-2, VZV
– Betaherpesviruses - CMV, HHV-6, HHV-7
– Gammaherpesviruses - EBV, HHV-8
 Set up latent or persistent infection following primary infection
 Reactivation are more likely to take place during periods
of immunosuppression
 Both primary infection and reactivation are likely to be
more serious in
immunocompromised patients.
 Herpesvirus Particle

HSV-2 virus particle. Note that

herpesviruse
all have identical
s and cannot
morphology from be each
distinguished
under electron other
microscopy.

(Linda Stannard, University of Cape Town, S.A.)

Viral Latency
Alphaherpesvirus Lesions
Alphaherpesvirus Lesions
Herpes Simplex
Viruses
 Properties
• Belong to the subfamily of
alphaherpesvirus
herpesviruses
• Double stranded DNA enveloped virus with
a
genome of around 150 kb
• The genome of HSV-1 and HSV-2 share 50 - 70%
homology.
• They also share several cross-reactive epitopes
with each other. There is also antigenic cross-
reaction with VZV.
• Man is the only natural host for HSV.
 Epidemiology (1)
• HSV is spread by contact, as the virus is shed in
saliva, tears, genital and other secretions.
• By far the most common form of infection results from
a kiss given to a child or adult from a person shedding
the virus.
• Primary infection is usually trivial or subclinical in
most individuals. It is a disease mainly of very young
children ie. those below 5 years.
• There are 2 peaks of incidence, the first at 0 - 5 years and
the second in the late teens, when sexual
activity commences.
• About 10% of the population acquires HSV infection
through the genital route and the risk is concentrated
in young adulthood.
 Epidemiology (2)
• Generally HSV-1 causes infection above the belt
and HSV-2 below the belt. In fact, 40% of clinical
isolates from genital sores are HSV-1, and 5% of
strains isolated from the facial area are HSV-2. This
data is complicated by oral sexual practices.
• Following primary infection, 45% of orally
infected individuals and 60% of patients with genital
herpes will experience recurrences.
• The actual frequency of recurrences varies widely
between individuals. The mean number of episodes
per year is about 1.6.
 HERPES GENITAL

Tersebar di seluruh dunia

Banyak inang
Replikasi pada banyak jenis sel
Infeksi pada organ genital ibu  neonatus
Siklus pertumbuhannya 8 – 16 jam
Sering pada orang dengan gangguan immunitas
Disebabkan infeksi virus Herpes simpleks-2
Herpes simpleks – 1  ???
HSV-1 dan HSV-2  berbeda secara biologik dan antigenik
Terdapat sedikit imunitas silang
Dapat ditemukan oral dan genital
SIFAT-SIFAT PENTING VIRUS HERPES
VIirion  Bulat, Diameter 150-200nm, kapsid
ikosahedral
Genom  DNA untai ganda, Linier, BM 95-150 juta,
124-235 kbp, urutan diulang
Protein  Lebih 35 protein dalam virion
Selubung  Glikoprotein, Reseptor Fc
Replikasi Inti, bertunas di membran inti
Ciri khas Mengkode banyak enzim; Infeksi laten,
bertahan secara tak terbatas pada hospes terinfeksi,
Diaktifkan kembali bila fungsi imunnya tertekan
INFEKSI RECURRENT  komplikasi kesehatan
berbahaya; beberapa menyebabkan kanker
REPLIKASI VIRUS HERPES
 KLASIFIKASI VIRUS HERPES MANUSIA
SUBFAMILIA SIFAT BIOLOGIK CONTOH

SIKLUS SITOPATOL INFEKSI GENUS NAMA NAMA UMUM

PERTUMBUH O GI LATEN KHUSUS
AN
Alfaherpesvirinae Pendek Sitolitik saraf SIMPLEX Herpesvirus HSV – 1
1 manusia
Herpesvirus HSV – 2
2 manusia
VARICELLO Herpesvirus
Varisela -
3 manusia
Zooster

Betaherpesvirinae Panjang sitomegalik Kelenjar, CYTOMEGA Herpesvirus Sitomegalovir

ginjal LO 5 manusia us

Jaringan ROSEOLO Herpesvirus Herpesvirus 6

limfoid 61 manusia manusia
Herpesvirus Herpesvirus
71 manusia 7 manusia

Gamaherpesvirina Variasi limfoprolifer Jaringan LYMPHOC Herpesvirus Virus Epstein

e atif limfoid RYPTO 4 manusia barr
Rhadino Herpesvirus Herpesvirus
81 manusia 8 manusia

1 SULIT DIKLASIFIKASI, VIRUS MENGINFEKSI LIMFOSIT, TETAPI GENOM MENYERUPAI SITOMEGALOVIRUS

PERBANDINGAN HSV-1 DAN HSV-2
CIRI KHAS HSV- HSV-
1 2
BIOKIMIA
Komposisi dasar DNA virus (Guanin –
Sitosin) 67% 69%
Densitas Berat Jenis DNA (g / cm3) 1,726 1,728
Densitas Berat Jenis virion (g / cm3) 1,271 1,267
Homologi antara virus DNAs - 50% - 50%

BIOLOGIK
Reservoir atau vektor hewan Tidak ada Tidak ada
Lokasi bentuk laten Ganglion trigeminal Ganglia sakral

EPIDEMIOLOGIK
Usia infeksi Anak kecil Dewasa muda
primer Penularan Kontak (Sering air Seksual
liur )
PERBANDINGAN HSV-1 DAN HSV-2
Ciri khas Hsv-1 Hsv-
KLINIK 2
Infeksi primer
Gingivostomatitis + -
Faringotonsilitis + -
Keratokonjungtivitis + -
Infeksi neonatus +

INFEKSI KAMBUHAN
Lesi dingin, DEemam lepuh + -
Keratitis + -

INFEKSI PRIMER ATAU KAMBUHAN

Herpes Kutaneus
Kulit sebelah atas pinggang + -
Kulit sebelah bawah pinggang - +
Lengan atau tangan + +
Herpes Whitlow + +
Eksema Herpetikum + -
Herpes Genital +
Ensefalitis Herpes + -
Meningitis Herpes +
 Pathogenesis
• During the primary infection, HSV spreads locally
and
short-lived a viraemia occurs, whereby the virus
disseminated in the body. Spread to is
the
ganglia occurs. to
craniospinal
• The virus then establishes latency in the craniospinal ganglia.
• The exact mechanism of latency is not known, it may be
true latency where there is no viral replication or viral
persistence where there is a low level of viral replication.
• Reactivation - It is known that many can
well triggers
provoke
psychological recurrence. These especially
stress, infection; include pneumococcal or
physical
and meningococcal, fever, irradiation; including sunlight,
a
and menstruation.
 PATOGENESIS

HSV  Infeksi sitolitik  Nekrosis sel + Peradangan  Mirip

dengan Varicella Zooster
Perubahan Histopat  Pembengkakan sel , Pembentukan
Badan Inklusi COWDRY TIPE A, Pembentukan sel
Raksasa berinti banyak
Cairan edema (Vesikuler) menumpuk diantara lapisan
epidermis dan dermis  Berisi sel yang bebas virus, sisa
sel radang
Di kulit  Cairan tersebut diabsorpsi membentuk keropeng

Sembuh tanpa jaringan parut
Pada sel mukosa  Vesikel pecah membentuk ulkus
yang dangkal
Herpes neonatal  Cuffyng perivaskuler dan daerah
nekrosis
hemorrhagik
 PATOGENESIS

HSV-1 dan HSV-2  Aseptik meningitis dan

ensefalitis pada orang dewasa

Herpes neonatus  75% HSV-2  ditularkan dari ibu

penderita ke anak melalui jalan kelahiran  Untuk
menghindar  Bedah Caecar

Herpes Neonatus :
Lokalisasi lesi pada kulit, mata, mulut
Ensefalitis dengan atau tanpa lesi kulit
Neonatal Disseminated Herpes  Organ–
organ dan SSP
 INFEKSI PRIMER

Port D’Entry  Kulit atau mukosa yang luka

HSV-1  Orofaring (Terutama pada anak-anak) dan Cold sores
(Virus reaktif  Virus menyebar melalui droplet/air liur
HSV-2  Veneral route (Seksual)  Infeksi primer  Ujung
saraf  Akar ganglion  Laten sampai akhir hidupnya 
Teraktivasi  Virus mengikuti jalannya axon kembali ke
perifer
 Berkembang biak di kulit dan sel mukosa ( Infeksi laten) 
Infeksi tidak begitu luas karena respon imunitas
HSV-2  Lesi genital primer pada penis/ vulva (3-7 hari
setelah infeksi) 
Ulcer yang sakit  Lymfonoduli lokal bengkak +
demam, Sakit kepala, malaise  2 minggu sembuh  Laten
(Dorsal akar ganglion saraf)  Reaktivasi  Lesi Recurrent
(Genital Cold sores)
 Clinical Manifestations
HSV is involved in a variety of clinical
manifestations which includes ;-
1. Acute gingivostomatitis
2. Herpes Labialis (cold sore)
3. Ocular Herpes
4. Herpes Genitalis
5. Other forms of cutaneous herpes
7. Meningitis
8. Encephalitis
9. Neonatal herpes
 Oral-facial Herpes
• Acute Gingivostomatitis
– Acute gingivostomatitis is the commonest manifestation of
primary
herpetic infection.
– The patient experiences pain and bleeding of the gums. 1 - 8
mm ulcers with necrotic bases are present. Neck glands are
commonly enlarged accompanied by fever.
– Usually a self limiting disease which lasts around 13 days.
• Herpes labialis (cold sore)
– Following primary infection, 45% of orally infected individuals
will experience reactivation. The actual frequency of recurrences
varies widely between individuals.
– Herpes labialis (cold sore) is a recurrence of oral HSV.
– A prodrome of tingling, warmth or itching at the site usually heralds
the recurrence. About 12 hours later, redness appears followed by
papules and then vesicles.
Gingivostomatitis
 Ocular Herpes
HSV causes a broad spectrum of ocular
disease, ranging from mild superficial lesions
involving the external eye, to severe sight-
threatening diseases of the inner eye. Diseases
caused include the following:-
– Primary HSV keratitis – dendritic ulcers
– Recurrent HSV keratitis
– HSV conjunctivitis
– Iridocyclitis, chorioretinitis and cataract
 Genital Herpes
• Genital lesions may be primary, recurrent or initial.
• Many sites can be involved which includes the penis, vagina,
cervix, anus, vulva, bladder, the sacral nerve routes, the spinal
and the meninges. The lesions of genital herpes are particularly
prone to secondary bacterial infection eg. S.aureus, Streptococcus,
Trichomonas and Candida Albicans.
• Dysuria is a common complaint, in severe cases, there may be
urinary retention.
• Local sensory nerves may be involved leading to the development of
a
radiculitis. A mild meningitis may be present.
• 60% of patients with genital herpes will experience
recurrences. Recurrent lesions in the perianal area tend to be more
numerous and persists longer than their oral HSV-1 counterparts.
 Herpes Simplex Encephalitis
• Herpes Simplex encephalitis is one of the most
serious complications of herpes simplex disease. There
are two forms:
• Neonatal – there is global involvement and the brain
is almost liquefied. The mortality rate approaches 100%.
• Focal disease – the temporal lobe is most
affected. This form
commonly
of the disease appears in children
and adults. It is possible that many of these cases
arise from reactivation of virus. The mortality rate is
high (70%) without treatment.
• It is of utmost importance to make a diagnosis of
HSE early. It is general practice that IV acyclovir is given
in all cases of suspected HSE before laboratory
results are available.
 Neonatal Herpes Simplex (1)
• Incidence of neonatal HSV infection varies
inexplicably from country to country e.g. from 1 in 4000
live births in the U.S. to 1 in 10000 live births in the UK
• The baby is usually infected perinatally during
passage through the birth canal.
• Premature rupturing of the membranes is a well
recognized
risk factor.
• The risk of perinatal transmission is greatest when there
is
a florid primary infection in the mother.
• There is an appreciably smaller risk from recurrent
lesions in the mother, probably because of the lower viral
load and the presence of specific antibody
 Neonatal Herpes Simplex (2)
• The spectrum of neonatal HSV infection varies from a
mild disease localized to the skin to a fatal
disseminated infection.
• Infection is particularly dangerous in premature infants.
• Where dissemination occurs, the organs most
commonly
involved are the liver, adrenals and the brain.
• Where the brain is involved, the prognosis is
particularly severe. The encephalitis is global and of such
severity that the brain may be liquefied.
• A large proportion of survivors of neonatal HSV infection
have residual disabilities.
• Acyclovir should be promptly given in all suspected
cases of neonatal HSV infection.