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)

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

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
Herpes Simplex Virus Type 1 (HSV-1)
Mainly causes oral herpes (cold sores), but can also cause genital herpes and encephalitis.
Herpes Simplex Virus Type 2 (HSV-2)
Primarily causes genital herpes and neonatal herpes.
Varicella-Zoster Virus (VZV or HHV-3)
Causes chickenpox (primary infection) and shingles (reactivation).
Epstein-Barr Virus (EBV or HHV-4)
Causes infectious mononucleosis and is associated with certain cancers.
Cytomegalovirus (CMV or HHV-5)
Causes asymptomatic infections or severe disease in immunocompromised and neonates.
Human Herpesvirus 6 (HHV-6)
Causes roseola infantum (exanthem subitum) in infants.
Human Herpesvirus 7 (HHV-7)
Similar to HHV-6, often causes mild febrile illness in children.
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
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Polymerase Chain Reaction (PCR):
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Most sensitive and specific test
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Detects viral DNA in lesions, blood, cerebrospinal fluid (CSF), or other body fluids
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Used for HSV, VZV, CMV, EBV, and others
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Viral Culture:
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Isolation of live virus from lesion swabs or fluids
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Useful but less sensitive and slower than PCR
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Direct Fluorescent Antibody (DFA) Test:
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Detects viral antigens in cells from lesions
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Tzanck Smear:
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Microscopic exam of lesion scrapings showing multinucleated giant cells
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Suggestive of HSV or VZV but not specific
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2. Serological Tests
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Antibody Detection (IgM, IgG):
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Indicates past exposure or recent infection
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Useful in diagnosing EBV, CMV, HSV (especially to distinguish primary vs recurrent infection)
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Not reliable for diagnosing acute localized HSV infections
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3. Blood Tests and Other Laboratory Findings
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Complete Blood Count (CBC):
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May show lymphocytosis in infectious mononucleosis (EBV)
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Liver Function Tests:
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May be elevated in EBV or CMV hepatitis
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CSF Analysis:
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In HSV encephalitis: lymphocytic pleocytosis, elevated protein, normal glucose
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PCR for HSV DNA in CSF is diagnostic
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Histopathology:
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Biopsy of lesions may show characteristic viral cytopathic effects
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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