Herpes Simplex Virus

Types of Herpes virus

1. Alpha-herpes viruses: HSV-1, HSV-2, VZV
2. Beta-herpes viruses: cytomegalovirus,HHV-6,HHV-7
3. Gamma herpes viruses: Epstein-Barr, virus, HHV-8

Introduction of Herpes simplex viruses (HSV)

• The herpes simplex virus is an infection that causes herpes, also known as HSV.
• HSV can appear and affect in various parts of the body, most commonly on the genitals or mouth.
• There are two types of the herpes simplex virus. HSV-1 and HSV-2.
• HSV-1, also known as oral herpes.
• It is responsible to cause cold sores and fever blisters around the mouth and on the face.
• HSV-2 is generally responsible for a genital herpes outbreak.
• HSV is spherical 150-200nm in diameter, icosahedral symmetry.
• HSV has large, double-stranded DNA genome encoding at least 100 proteins. DNA is linear, 125-240kb, reiterated sequences.
• The genome is packaged within an icosahedral protein shell called nucleocapsids.
• Herpes viruses’ genomes possess’ terminal and internal repeated sequences. HSVs undergo genome rearrangements, giving rise to different genome isomers.
• The nucleocapsids are covered by a layer of protein called the tegument, which in turn is enclosed within a lipid-containing envelope.
• The envelope contains about a dozen glycoproteins in addition to lipid.
• HSV use host cell nucleus for viral gene transcription, viral DNA replication and assembly of progeny nucleocapsids.
• Viral proteins are made in the cytoplasm of the host cell.
• Envelopment of the nucleocapsids occurs at the inner nuclear membrane of the host cell and acquisition of the final envelope at a cytoplasmic membrane.

Pathogenesis

• The virus is acquired through oral –oral contact, oral –genital contact or, genital – genital contact.
• HSV are fragile and susceptible to drying and inactivation by heat, mild detergents, and solvents.
• Mucous membranes of the mouth eye, genitals, respiratory tracts, and anus are the sites most readily infected by the virus under normal conditions.
• Thick keratin layer of the superficial epidermis prevents HSV to the host cell receptors.
• Although HSV encodes many enzymes, there are still dependent on cellular enzymes, energy, and metabolic resources.
• Virion interacts with specific cell surface cell receptors through glycoproteins that project from the viral envelope and start infection of the host cell.
• Alpha- herpes virus can bind to cells through the interaction of viral glycoproteins with heparin sulfate chains of cell surface proteoglycans.
• HSV-1 and HSV-2 have several kinds of entry receptors and they use any one of them.
• Binding of viral glycoproteins to an entry receptors triggers fusion of the viral envelope with a cell membrane.
• Fusion causes a release of the viral nucleocapsids to nuclear pores.
• The viral genome is released into the nucleus.
• Mucosal cells support virus replication immediately; the viral genes will be transcribed leading to the synthesis of viral proteins, replication of viral genomes and assembly of progeny viruses.
• If the host cell is latently infected, the viral genome circularizes in the nucleus and persists as an episome with only minimal transcription of viral genes.
• In a case of HSV, the virus gains access to nerve cell ending and to the nerve cell bodies in peripheral ganglia, where latent infections are established.

Causes of Herpes simplex virus

• The herpes simplex virus is a contagious virus that is commonly transmitted from person to person through direct contact.
• Infection with HSV-1 occurs with general interactions such as eating from the same utensils, sharing lip balm, or kissing.
• From the infected adult, children will often contract HSV-1 from early contact. Then the children carry the virus with them for the rest of their life.
• When an infected person is experiencing an outbreak of this virus, it has the capacity to spread more quickly.
• Additionally, it is also possible to get an infection of genital by genital herpes from HSV-1 if the individual has had cold sores and performed sexual activities during that time.
• HSV-2 is transmitted through forms of sexual contact with a person who is suffering from an HSV-2 infection.

Signs and symptoms of Herpes Simplex Virus

Although someone may not have visible sores or symptoms of this virus but they may still be infected by the virus and may transmit the virus to others. Some of the signs and symptoms associated with this virus are as follows:

• Appearance of blistering sores (in the mouth or on the genitals)
• pain during urination indicates genital herpes
• the occurrence of itching

Additionally, symptoms that are similar to the flu are also seen. The symptoms are as follows;

• Fever
• Swollen lymph nodes
• Headaches
• Tiredness
• Lack of appetite.

HSV can also spread to the eyes, causing a condition called herpes keratitis. This can cause symptoms such as;

• eye pain
• discharge
• gritty feeling in the eye.

Host defenses

• The host defenses do not prevent latent infection and cannot estimate latent virus because latently infected cells apparently do not trigger immune responses.
• An infection with HSV-1 and Hsv-2 induces immediate innate responses such as activation of neutrophils, NK cells and production of interferon, and other cytokines.
• Antibodies to viral proteins are produced and T-lymphocytes are amplified in number and activated.
• Cell-mediated immune mechanisms are most important for recovery from disease.
• Both HSV and VZV are destructive of the epithelial cells in which they replicate in a skin and mucous membranes.
• HSV lesions are usually localized, with a spread of virus restricted to regional nerves.
• Inflammation of the nerves can occur during the acute phase of the disease, causing symptoms of itching, tingling, burning, or pain.
• Reactivated HSV travels down the axonal process to infect contagious mucocutaneous epithelial cells.
• Factors triggering the reactivation of latent HSV:

1. Sunburn
2. Systematic infection
3. Immune impairment
4. Emotional stress.

Risk of herpes simplex infection

The risk of HSV is almost entirely based on exposure to the infection. Anyone can be infected with HSV, regardless of age. People are more at risk with HSV when they participate in risky and unsafe sexual behavior without the use of protection, such as condoms. There are other various risk factors for HSV-2 include:

• To have multiple sex partners
• Female are more sensitive to this infection
• If an infected mother gives birth to a child having an outbreak of genital herpes, it can expose the baby to both types of HSV, and may put them at risk for serious complications.
• infection (STI)
• having a weakened immune system

Clinical features

• Corneal infections
• Primary genital herpes caused by HSV-2 can progress to meningitis.
• HSV-1 can pass to CNS from peripheral nerves causing life-threatening encephalitis.
• Newborn neurological disease.

Clinical diagnosis

Clinically, the infection is diagnosed by the inflammation of gums appearance of;

• Ulcerative lesions on oropharynx, gingivitis (inflammation of gums), gingivostomatitis and cluster of vesicles localized at the border of a lip in recurrent disease.
• Dendritic keratitis, corneal ulcers of vesicles on the eyelids.
• Vesiculoulcerative lesions on penis or cervix, vulva, vagina and perineum of the female.

Diagnosis of Herpes simplex diagnosis

The diagnosis of HSV virus is generally diagnosed with a physical examiner; they check the infected body for sores and see the current appearance of symptoms. HSV testing is also done by herpes culture. The diagnosis confirms if sores appear on a genital organ. During this test, a swab sample of fluid from the sore is taken and then sends it to a laboratory for testing.

When there are no sores present, blood tests is preferred to look for antibodies to HSV-1 and HSV-2 to diagnose these infections.

Laboratory diagnosis

1. Cytopathology

• Scrapings or biopsy obtained from the base of a vesicle is stained with Giemsa`s stain.
• The presence of multinucleated giant cells with eosinophilic granules in nucleus indicated that herpes virus (HSV-1, HSV-2 or VZV) is present, distinguishing lesions from those caused by coxsackieviruses & nonviral entities.

2. Isolation and identification of virus

• The virus can be isolated from fibroblast & epithelial cell lines from animals or humans.
• Cytopathic effects usually occur in only 2-3 days.
• Culture fluid is identical by neutralization test and immunofluorescence test.
• Typing of HSV isolates may be done using a monoclonal antibody or by restriction endonucleases analysis of viral DNA.

3. Polymerase chain reaction

PCR amplification of viral DNA from CSF is highly sensitive & specific.

4. Serology

• Serodiagnosis is effective 4-7 days after infection.
• Neutralization test, immunofluorescence, and ELISA.

Treatment

• Acyclovir
• Famciclovir

Prevention

• Avoid sexual contact during active genital herpes infection.
• No vaccine available

REFERENCE

M, Cheesbrough. Medical Laboratory Manual for Tropical Countries. Vol. 2. London: ELBS, 2007.

D, Grenwood, Slack RCB and Peutherer J. Medical Microbiology. Dunclude Livingstone: ELBS, 2001.

Tille, P.Diagnostic Microbiology.13th. Elsevier, 2014