Herpes viruses

Content of This Page

1- Introduction

2- Causes

3- Symptoms

4- Types of Herpesviruses

5- Investigations & Lab Results

6- Complications

7- Treatment

Introduction

The Herpesviridae family is a large group of DNA viruses known for their ability to cause lifelong infections in humans and animals. These viruses are characterized by their double-stranded DNA genome, an icosahedral capsid, and an outer lipid envelope derived from the host cell membrane.

A hallmark of herpesviruses is their capacity to establish latent infections—after an initial active infection, the virus remains dormant within specific cells (usually nerve or immune cells) and can reactivate later, causing recurrent disease.

The herpesvirus family includes viruses that infect humans and cause a wide spectrum of diseases, ranging from mild mucocutaneous lesions to severe systemic illnesses and cancers. They are grouped into three subfamilies based on their biological properties:

  • Alpha-herpesvirinae: Fast-replicating viruses that establish latency in sensory nerve ganglia (e.g., HSV-1, HSV-2, Varicella-Zoster Virus)

  • Beta-herpesvirinae: Slow-growing viruses with latency in secretory glands and lymphoid tissues (e.g., Cytomegalovirus, HHV-6, HHV-7)

  • Gamma-herpesvirinae: Latent in lymphoid cells and associated with some cancers (e.g., Epstein-Barr Virus, Kaposi’s Sarcoma-associated Herpesvirus)

Herpes Labialis © image from www.researchgate.net

Causes

  • Herpes Simplex Virus type 1 (HSV-1)

    • Causes oral herpes (cold sores), sometimes genital herpes, and encephalitis

    • Transmitted by close contact, saliva, or skin-to-skin contact

  • Herpes Simplex Virus type 2 (HSV-2)

    • Causes genital herpes

    • Transmitted primarily via sexual contact

  • Varicella-Zoster Virus (VZV)

    • Causes chickenpox (primary infection) and shingles (reactivation)

    • Spread by respiratory droplets or direct contact with lesions

  • Epstein-Barr Virus (EBV)

    • Causes infectious mononucleosis

    • Spread through saliva (“kissing disease”)

  • Cytomegalovirus (CMV)

    • Causes asymptomatic infections or severe disease in immunocompromised patients and neonates

    • Spread by body fluids including saliva, urine, blood, and sexual contact

  • Human Herpesvirus 6 (HHV-6) and 7 (HHV-7)

    • Cause roseola infantum and related febrile illnesses in children

    • Spread mainly through saliva

  • Kaposi’s Sarcoma-Associated Herpesvirus (KSHV or HHV-8)

    • Associated with Kaposi’s sarcoma and certain lymphomas

    • Transmitted via sexual contact, saliva, and blood

Shingles © image from www.researchgate.net

Symptoms

1. Herpes Simplex Virus (HSV-1 and HSV-2):

  • Primary infection: Painful vesicular lesions on or around the mouth (HSV-1) or genital area (HSV-2)

  • Burning, itching, or tingling before lesions appear

  • Fever, malaise, and swollen lymph nodes in primary infections

  • Recurrent outbreaks: similar but usually milder lesions, often preceded by tingling or itching

  • In severe cases, HSV can cause encephalitis or neonatal herpes (life-threatening)

2. Varicella-Zoster Virus (VZV):

  • Chickenpox (varicella): Fever, malaise, and a widespread itchy vesicular rash in various stages (macules, papules, vesicles, crusts)

  • Shingles (herpes zoster): Painful, unilateral, vesicular rash localized to a dermatome; can cause postherpetic neuralgia

3. Epstein-Barr Virus (EBV):

  • Infectious mononucleosis: Fever, sore throat, swollen tonsils, fatigue, enlarged lymph nodes, and splenomegaly

  • Sometimes rash, hepatitis, or neurological symptoms

4. Cytomegalovirus (CMV):

  • Often asymptomatic in healthy individuals

  • In immunocompromised: fever, pneumonia, hepatitis, retinitis (vision loss), colitis

  • Congenital CMV: hearing loss, developmental delays

5. Human Herpesvirus 6 and 7 (HHV-6, HHV-7):

  • Roseola infantum (exanthem subitum): Sudden high fever followed by a pink rash as fever subsides, mainly in infants and young children

6. Kaposi’s Sarcoma-Associated Herpesvirus (HHV-8):

  • Skin lesions (purple/red patches or nodules) characteristic of Kaposi’s sarcoma

  • May involve mucous membranes, lymph nodes, and internal organs, especially in immunocompromised patients

Types of Herpesviruses

  1. Herpes Simplex Virus Type 1 (HSV-1)

    • Mainly causes oral herpes (cold sores), but can also cause genital herpes and encephalitis.

  2. Herpes Simplex Virus Type 2 (HSV-2)

    • Primarily causes genital herpes and neonatal herpes.

  3. Varicella-Zoster Virus (VZV or HHV-3)

    • Causes chickenpox (primary infection) and shingles (reactivation).

  4. Epstein-Barr Virus (EBV or HHV-4)

    • Causes infectious mononucleosis and is associated with certain cancers.

  5. Cytomegalovirus (CMV or HHV-5)

    • Causes asymptomatic infections or severe disease in immunocompromised and neonates.

  6. Human Herpesvirus 6 (HHV-6)

    • Causes roseola infantum (exanthem subitum) in infants.

  7. Human Herpesvirus 7 (HHV-7)

    • Similar to HHV-6, often causes mild febrile illness in children.

  8. Kaposi’s Sarcoma-Associated Herpesvirus (KSHV or HHV-8)

    • Associated with Kaposi’s sarcoma and certain lymphomas, mainly in immunocompromised patients.

Investigations & Lab Results

1. Direct Detection of Virus or Viral Components

  • Polymerase Chain Reaction (PCR):

    • Most sensitive and specific test

    • Detects viral DNA in lesions, blood, cerebrospinal fluid (CSF), or other body fluids

    • Used for HSV, VZV, CMV, EBV, and others

  • Viral Culture:

    • Isolation of live virus from lesion swabs or fluids

    • Useful but less sensitive and slower than PCR

  • Direct Fluorescent Antibody (DFA) Test:

    • Detects viral antigens in cells from lesions

  • Tzanck Smear:

    • Microscopic exam of lesion scrapings showing multinucleated giant cells

    • Suggestive of HSV or VZV but not specific

2. Serological Tests

  • Antibody Detection (IgM, IgG):

    • Indicates past exposure or recent infection

    • Useful in diagnosing EBV, CMV, HSV (especially to distinguish primary vs recurrent infection)

    • Not reliable for diagnosing acute localized HSV infections

3. Blood Tests and Other Laboratory Findings

  • Complete Blood Count (CBC):

    • May show lymphocytosis in infectious mononucleosis (EBV)

  • Liver Function Tests:

    • May be elevated in EBV or CMV hepatitis

  • CSF Analysis:

    • In HSV encephalitis: lymphocytic pleocytosis, elevated protein, normal glucose

    • PCR for HSV DNA in CSF is diagnostic

  • Histopathology:

    • Biopsy of lesions may show characteristic viral cytopathic effects

Complications

1. Herpes Simplex Virus (HSV) Complications

  • Herpes encephalitis: Severe brain inflammation, potentially fatal without treatment

  • Keratitis: Eye infection leading to scarring and possible vision loss

  • Neonatal herpes: Disseminated infection in newborns causing severe morbidity or death

  • Herpetic whitlow: Painful finger infection

  • Eczema herpeticum: Widespread skin infection in patients with eczema

  • Recurrent painful lesions: Impact quality of life

2. Varicella-Zoster Virus (VZV) Complications

  • Postherpetic neuralgia: Persistent nerve pain after shingles resolves

  • Disseminated zoster: Severe widespread rash in immunocompromised patients

  • Pneumonia: Especially in adults with chickenpox

  • Encephalitis and meningitis

  • Congenital varicella syndrome: When maternal infection occurs during pregnancy

3. Epstein-Barr Virus (EBV) Complications

  • Splenic rupture during infectious mononucleosis

  • Chronic active EBV infection

  • Burkitt lymphoma, nasopharyngeal carcinoma, Hodgkin lymphoma

  • Autoimmune hemolytic anemia and thrombocytopenia

4. Cytomegalovirus (CMV) Complications

  • Congenital CMV infection: Hearing loss, developmental delay

  • Retinitis: Leading to blindness in AIDS patients

  • Pneumonitis, colitis, hepatitis in immunocompromised

  • Graft rejection and dysfunction in transplant patients

5. Human Herpesvirus 6 and 7 (HHV-6, HHV-7) Complications

  • Rare but can cause encephalitis and pneumonitis in immunocompromised

  • Reactivation may contribute to transplant complications

6. Kaposi’s Sarcoma-Associated Herpesvirus (HHV-8) Complications

  • Kaposi’s sarcoma: Malignant vascular tumors, common in HIV/AIDS

  • Primary effusion lymphoma and multicentric Castleman disease

Treatment

1. Herpes Simplex Virus (HSV-1 and HSV-2)

  • First-line drugs:

    • Acyclovir (oral, topical, or IV for severe cases)

    • Valacyclovir (better oral bioavailability)

    • Famciclovir

  • Used for primary and recurrent infections, genital herpes, and encephalitis

  • For frequent recurrences, suppressive antiviral therapy may be recommended

2. Varicella-Zoster Virus (VZV)

  • Acute chickenpox: Usually supportive care unless high-risk patients, then antiviral (acyclovir)

  • Shingles: Early treatment with acyclovir, valacyclovir, or famciclovir to reduce severity and prevent postherpetic neuralgia

  • Pain management is important; sometimes nerve blocks or gabapentin for postherpetic neuralgia

3. Epstein-Barr Virus (EBV)

  • No specific antiviral treatment for infectious mononucleosis

  • Supportive care: hydration, rest, analgesics, corticosteroids for severe complications

4. Cytomegalovirus (CMV)

  • Ganciclovir or valganciclovir are first-line agents for severe or systemic infections

  • Foscarnet or cidofovir for resistant cases

  • Used mainly in immunocompromised patients or congenital infections

5. Human Herpesvirus 6 and 7 (HHV-6, HHV-7)

  • Usually self-limited (roseola) in healthy individuals

  • Antivirals like ganciclovir may be used in immunocompromised patients with severe disease

6. Kaposi’s Sarcoma-Associated Herpesvirus (HHV-8)

  • Treatment focuses on managing Kaposi’s sarcoma with antiretroviral therapy (if HIV-positive), chemotherapy, radiation, or immunotherapy

  • No specific antiviral targeting HHV-8

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