HERPES SIMPLEX

VIRUS

OVERVIEW INTRODUCTION

EPIDEMIOLOGY AND TRANSMISSION

STRUCTURE

REPLICATION

PATHOGENESIS AND CLINICAL SIGNIFICANCE

LABORATORY DIAGNOSIS

TREATMENT AND PREVENTION

INTRODUCTION

Herpes (Greek: creep or crawl)

Herpes simplex viruses belong to the ubiquitous Herpesviridae family

Human herpes simplex virus (HSV) causes contagious infection with a large reservoir in the general population

Herpesviruses are able to establish lifelong persistent infections in their hosts and undergo periodic reactivation ; incurable

HSV has a potential for significant complications in the immunocompromised host

INTRODUCTION

HSV-1 is normally associated with orofacial infections and encephalitis

HSV-2 usually causes genital infections and can be transmitted from infected mothers to neonates

Both viruses establish latent infections in sensory neurons and, upon reactivation, cause lesions at or near point of entry into the body

CLASSIFICATION OF HUMAN HERPESVIRUSES

Biologic properties

Examples

Subfamily(“herpesvirinae)

Growth cycle and cytopathology

Latent infections

Genus(“virus)

Official name (“Human herpesvirus”)

Common name

Alpha Short, cytolytic Neurons Simplex 1 Herpes simplex virus type 1

2 Herpes simplex virus type 2

Varicello 3 Varicella-zoster virus

Beta Long, cytomegalic Glands, kidneys

Cytomegalo 5 Cytomegalovirus

Long, lymphoproliferative

Lymphoid tissue

Roselo 6 Human herpesvirus 6

7 Human herpesvirus 7

Gamma Variable, lymphoproliferative

Lymphoid tissue

Lymphocrypto 4 Epstein-Barr virus

Rhadino 8 Kaposi's sarcoma-associated herpesvirus

EPIDEMIOLOGY

HSV-associated diseases are among the most wide-spread infections affecting nearly 60-95% of human adults

No animal reservoirs or vectors

Highest incidence of HSV-1 infection occurs among children 6 months to 3 years of age

70–90% of persons thus acquire type 1 antibodies by adulthood

Primary infection by HSV-2 is more common in young adults

TRANSMISSION

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

HSV-1 is spread by contact, usually by infected saliva

HSV-1 primarily infects skin above the waist

HSV-2 is transmitted sexually or from a maternal genital infection to a newborn

HSV-2 primarily infects skin below the waist

STRUCTURE

Virions are spherical, 150-200nm in diameter

HSV-1 and HSV-2 contains

i. an envelope- derived from the nuclear membrane of the infected cell; contains viral glycoproteins

ii. a tegument—an amorphous layer of proteins that surround the capsid

iii. an icosahedral capsid

iv. Genome (linear, a large double-stranded viral DNA; encoding70-200 proteins)

REPLICATION

i. Virus adsorption and penetration

ii. Viral DNA replication and nucleocapsid assembly

iii. Acquisition of the viral envelope

iv. Latency

PATHOGENESIS

HSV causes cytolytic infections

Pathologic changes are due to necrosis of infected cells together with the inflammatory response

Viral cytopathy

PATHOGENESIS

Ballooning of infected cells

Production of Cowdry type A intranuclear (Lipschutz) inclusion bodies

Margination of chromatin

Formation of multinucleated giant cells

CLINICAL SIGNIFICANCE

HSV-1 Acute gingivostomatitis

Recurrent herpes labialis (cold sores)

Herpetic whitlow

Keratoconjunctivitis

Encephalitis

HSV-2 Genital herpes Neonatal herpes

(may be by HSV-1 aswell)

CLINICAL SIGNIFICANCE

Primary infections of the upper body

Fig. Herpes simplex gingivostomatitis

Fig. Herpetic whitlow

Fig. Recurrent herpes labialis (cold sores) Fig. Keratoconjunctivitis

CLINICAL SIGNIFICANCE

Primary infections of the genital tract

Fig. Genital herpes simplex infections

CLINICAL SIGNIFICANCE

Latency HSV-1: Trigeminal ganglia HSV-2: Sacral ganglia

Fig. Primary and recurrent herpes simplex infections

CLINICAL SIGNIFICANCE

Reactivation Hormonal changes, fever, and physical damage Severity of any systemic symptoms is considerably

less than that of a primary infection Many recurrences are characterized by shedding of

infectious virus in the absence of visible lesions HSV-1:

Reactivation frequency- none to several a yearHerpes labialis or cold sores, fever blisters

HSV-2:Reactivation frequency- monthlyAsymptomatic; viral shedding

LABORATORY DIAGNOSIS

A. Cytopathology:

A rapid cytologic method

Scrapings obtained from the base of a vesicle is stained with 1% aq. solution of toluidine blue ‘0’ for 15 seconds

Presence of multinucleated giant cells or ‘Tzanck cells’ = + HSV

Intranuclear inclusion bodies with Giemsa-stained smears

LABORATORY DIAGNOSISB. Isolation and identification:

Inoculation of tissue cultures in human diploid fibroblasts is preferred for viral isolation

Typical cytopathic changes may be seen in 24-48 hrs

C. Polymerase chain reaction:

D. Serology: Antibodies appear in 4–7 days after infection; reach a

peak in 2–4 weeks Rise in Ab titre may be demonstrated by ELISA or

complement fixation tests

TREATMENT AND PREVENTION

Aciclovir, Valaciclovir, Famciclovir

Asymptomatic shedding is frequent in patients with genital herpes

Transmission can be reduced by:

avoidance of contact with potential virus-shedding lesions

safe sexual practice antiviral therapy

REFERENCES Harvey RA, Champe PC, Fischer BD. Lippincott’s

Illustrated Reviews: Microbiology. 2nd edition. 2007. Jawetz, Melnick & Adelberg. Medical Microbiology.

The McGraw-Hill Companies. 25th edition Richard J Whitley, Bernard Roizman. Herpes

simplex virus infections. Lancet. 2001; 357: 1513–18

Fatahzadeh M & Schwartz RA. Human herpes simplex virus infections: Epidemiology, pathogenesis, symptomatology, diagnosis and management. JAM ACAD DERMATOL. 2007; 737-763

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