Herpes virus

 

Herpes virus

Herpes viruses are DNA viruses; they are the leading cause of human viral disease, second only to influenza and cold viruses. Herpes (Latin herpes, Greek herpein, which means to creep). This reflects the creeping or spreading nature of the skin lesions caused by many herpes virus types. It is capable of causing overt disease or remaining silent for many years, only to be reactivated, for example, as shingles.

The Herpesviridae family is a large group of double-stranded DNA viruses. They are classified into three subfamilies: Alpha, Beta, and Gamma herpesviruses.

1. Alpha-herpesviruses (α-herpesvirinae)

• Characteristics:
• Rapid replication cycle
• Latency in sensory nerve ganglia
• Broad host range
• Examples:
• Herpes simplex virus type 1 (HSV-1) → oral herpes
• Herpes simplex virus type 2 (HSV-2) → genital herpes
• Varicella-zoster virus (VZV / HHV-3) → chickenpox (primary), shingles (reactivation)

2. Beta-herpesviruses (β-herpesvirinae)

• Characteristics:
• Slow replication cycle
• Latency in monocytes, lymphocytes, kidney, secretory glands
• Cause enlargement of infected cells (cytomegaly)
• Examples:
• Human cytomegalovirus (CMV / HHV-5) → congenital infections, opportunistic disease in immunocompromised
• Human herpesvirus 6 (HHV-6) → roseola infantum
• Human herpesvirus 7 (HHV-7) → also linked to roseola-like illness

3. Gamma-herpesviruses (γ-herpesvirinae)

• Characteristics:
• Latency in B-lymphocytes
• Associated with tumors (oncogenic potential)
• Examples:
• Epstein-Barr virus (EBV / HHV-4) → infectious mononucleosis, Burkitt’s lymphoma, nasopharyngeal carcinoma
• Kaposi’s sarcoma-associated herpesvirus (KSHV / HHV-8) → Kaposi’s sarcoma, primary effusion lymphoma

Herpes Simplex Virus (HSV)

HSV belongs to the alpha herpesvirus group. HSV are of two types, HSV-1 and HSV-2, with very similar characteristics. The overall sequence homology between HSV-1 and HSV-2 is about 50%. HSV-1 has tropism for oral epithelium, while HSV-2 has tropism for genital epithelium. HSV-1: primarily causes oral herpes, and is generally responsible for cold sores and fever blisters around the mouth and on the face. HSV-2: primarily causes genital herpes, and is generally responsible for genital herpes outbreaks.

HSV-1 (Herpes Simplex Virus Type 1): Primarily causes oral herpes, including cold sores or fever blisters around the mouth. It can also cause genital herpes through oral-genital contact.

HSV-2 (Herpes Simplex Virus Type 2): Primarily causes genital herpes, leading to sores or blisters in the genital and anal areas.

 Morphology 

Family: Herpesviridae

• Structure:
• Genome: Double-stranded DNA (linear).
• Capsid: Icosahedral symmetry, composed of 162 capsomeres.
• Tegument: Protein layer between the capsid and envelope, aiding in virus replication.
• Envelope: Lipid bilayer derived from host cells, studded with glycoproteins (e.g., gB, gC, gD, and gE) important for attachment and immune evasion.
• Size: 120-200 nm in diameter.

Replication of Herpes

Attachment and Entry-

The replication of Herpes Simplex Virus begins when the viral glycoproteins present on its envelope, such as gB, gC, gD, and gH/gL, interact with specific receptors on the host cell surface, including heparan sulfate and nectin-1. 

Penetration

After attachment, the viral envelope fuses with the cell membrane, and the viral capsid (protein shell) carrying the DNA enters the cytoplasm.

Transport to the Nucleus

Once inside the cell, the viral capsid does not stay in the cytoplasm. It moves along tiny cellular “tracks” (microtubules) until it reaches the nucleus. At the nuclear pore, the capsid releases the viral DNA into the nucleus, where further steps of replication will take place.

Biosynthesis

In the nucleus, the viral DNA becomes circular and begins making viral proteins in a stepwise manner. First, immediate early proteins are produced, which regulate viral activity. Then, early proteins are made, which include enzymes needed for copying the DNA, making more DNA. Finally, late proteins are produced, which are mainly structural proteins, the Capsid that will form the new virus particles

Assembly

The newly made DNA is inserted into empty protein shells (capsids) inside the nucleus. This process forms immature virus particles that still need their final outer covering (envelope).

Maturation and Release

The capsids move out of the nucleus and pick up their envelope by budding through membranes in the cell that contain viral glycoproteins. These mature viruses are then carried to the cell surface and released by exocytosis, or sometimes by breaking open the cell.

Latency

Unlike many viruses that immediately destroy host cells, HSV has a special feature: it can remain hidden in nerve cells without causing active infection. In this latent state, the viral DNA stays in the nucleus but only produces a few special RNA molecules called latency-associated transcripts (LATs). No new viruses are formed during latency. Later, under stress, fever, or weakened immunity, the virus can “wake up” and start a new cycle of replication, causing recurrent infection.

Pathogenesis of Herpes

• Entry → virus enters via mucosa/skin.
• Local replication → vesicles and ulcers form.
• Neural spread & latency → virus establishes latency in sensory ganglia.
• Reactivation → virus returns to skin/mucosa causing recurrent lesions.
• Severe disease → in immunocompromised, can cause encephalitis, keratitis, or disseminated infection.

Herpes Simplex Virus (HSV) usually enters the body through mucous membranes (such as the mouth, eyes, or genitals) or broken skin. At the site of entry, the virus infects epithelial cells, where it multiplies and causes local cell damage. This leads to the formation of painful blisters or ulcers, which are the typical lesions of herpes infection.

After primary infection, HSV spreads to nearby sensory nerve endings and travels along the nerves to reach the nerve cell bodies in ganglia (trigeminal ganglion for HSV-1 and sacral ganglion for HSV-2). Here, the virus becomes latent and remains hidden inside the neurons for the lifetime of the host. During latency, no infectious particles are produced, but the viral DNA stays inside the nucleus of neurons.

Reactivation can occur when the immune system is weakened or due to triggers like stress, fever, or sunlight. When reactivated, the virus travels back along the nerve fibers to the skin or mucosa, causing recurrent lesions at or near the original site of infection. These recurrent infections are usually milder than the primary infection but are an important feature of HSV pathogenesis.

In immunocompromised individuals, HSV can cause more severe disease, including encephalitis, keratitis (eye infection leading to blindness), or widespread skin infections.

Transmission

Herpes spreads through direct contact with an infected person, even if they are asymptomatic. Common ways of transmission include:

• HSV-1:
• Saliva (kissing, sharing utensils, or towels).
• Oral-genital contact.
• HSV-2:
• Sexual contact (vaginal, anal, or oral).
• Skin-to-skin contact in the genital area.

Both types of HSV can remain dormant in the body and reactivate under certain conditions.

2. Symptoms

Oral Herpes (HSV-1):

• Blisters or cold sores around the mouth and lips.
• Tingling, itching, or burning sensations before blisters appear.
• Fever, sore throat, or swollen lymph nodes (especially in first-time infections).

Genital Herpes (HSV-2):

• Painful blisters or sores in the genital or anal area.
• Itching or tingling in the affected area.
• Pain during urination.
• Flu-like symptoms (fever, body aches) during initial outbreaks.

Asymptomatic Cases:

• Many people with HSV do not experience noticeable symptoms but can still transmit the virus.

Laboratory Diagnosis

Specimen collection

• The best specimens are fluid from vesicles, swabs from ulcers, throat or genital swabs, cerebrospinal fluid (in suspected encephalitis), and corneal scrapings (for keratitis).

• Ø  Tzanck smear → multinucleated giant cells.
• Ø  Culture → cytopathic effect.
• Ø  Antigen detection → immunofluorescence/ELISA.
• Ø  PCR → most sensitive, especially for encephalitis.
• Ø  Serology → IgM (recent), IgG (past infection).

1. Direct Microscopy
• Tzanck smear: A smear is made from the base of a vesicle, stained, and examined under the microscope. The presence of multinucleated giant cells suggests HSV infection, but this test is not very specific.

2. Antigen Detection
• Viral antigens can be detected directly from lesion samples using immunofluorescence or ELISA. This method is faster than culture.

3. Virus Isolation (Culture)
• The specimen is inoculated into cell cultures (e.g., Vero cells) . HSV produces a characteristic cytopathic effect (CPE): cells become rounded, enlarged, and form multinucleated giant cells. Culture is considered a reliable diagnostic method but takes time.

4. Molecular Methods
• PCR (Polymerase Chain Reaction) is the most sensitive and specific test. It is especially important for detecting HSV in encephalitis or cases with low viral load.

5. Serology
• Blood tests can detect HSV antibodies (IgM and IgG). IgM indicates recent infection, while IgG shows past exposure. Serology is not very useful for routine diagnosis but may help in epidemiological studies.

 Prevention and Control

A. Prevention

1. Personal Hygiene:
• Avoid direct contact with active lesions.
• Avoid sharing personal items like razors or towels.
2. Safe Sexual Practices:
• Use condoms during sexual activity.
• Avoid sexual contact during outbreaks.
3. Vaccination:
• Currently under development; no licensed HSV vaccine available.
4. Neonatal Prevention:
• Cesarean delivery in pregnant women with active genital herpes to prevent neonatal transmission.

B. Control

1. Antiviral Medications:
• Acyclovir, valacyclovir, and famciclovir reduce symptoms, duration, and viral shedding.
• Prophylactic antivirals for frequent recurrences.
2. Public Health Measures:
• Education about HSV transmission and symptoms.
• Screening high-risk individuals (e.g., pregnant women).

C. Special Considerations

• Immunocompromised Patients:
• Aggressive antiviral therapy is required.
• Prevention of secondary infections.
• Neonatal Herpes:
• Immediate antiviral therapy (intravenous acyclovir).