Human Herpesviruses Classification

Herpes Viruses

• The herpes viruses are a group of large, DNA-enveloped viruses.
• Features of herpes viruses include virion morphology, basic replication, and the ability to cause latent and recurrent infections.
• Human herpes viruses are categorized into three subfamilies (alpha, beta, and gamma) based on viral characteristics (genome, tissue tropism, etc.).

Classification of Human Herpesviruses

• The Herpesviridae family includes Herpesvirinae subfamily.
• Various subfamilies and genera of Human Herpesviruses are classified.
• Official names for each genus and subfamily are listed alongside common names.

Subfamily Alpha herpes virinae

• Viruses in this subfamily primarily infect mucoepithelial cells and neurons .
• Transmission through close contact is common.
• Some viruses are sexually transmitted.

Subfamily Beta herpes virinae

• These viruses primarily infect monocyte, lymphocyte, and epithelial cells.
• Transmission through close contact, blood transfusions, and tissue transplants is common.

Subfamily Gamma herpes virinae

• These viruses mainly infect B cells and epithelial cells.
• Spread through saliva and close contact are typical transmission modes.

Herpesviruses' Viral Replication and Persistence

• Herpesviruses encode enzymes (DNA polymerase) promoting viral DNA replication.
• They are easily targeted by antiviral drugs.
• Release mechanisms include exocytosis, cell lysis, and cell-cell bridges.
• Herpesviruses can persist in host cells indefinitely, typically in the nucleus.
• Varicella-zoster and herpes simplex viruses establish latent infections in neurons.
• Herpes zoster (shingles) is a common reactivation of varicella-zoster virus.

Herpes Simplex Viruses (HSV) 1 & 2

• HSV is the first human herpesvirus recognized, derived from the Greek word "herpes" meaning to creep.
• It is extremely widespread in humans.
• It has a broad host range, replicating in numerous cell types and infecting various animals.
• HSV grows rapidly and is highly cytolytic, responsible for a spectrum of diseases, from gingivostomatitis to keratoconjunctivitis and encephalitis.
• HSV-1 is usually associated with infections above the waist, while HSV-2 is associated with infections below the waist.
• HSV-1 and HSV-2 significantly differ in their growth characteristics and antigenicity as well as their modes of transmission.
• HSV-1 is generally spread by saliva, and HSV-2 is typically transmitted sexually.

Herpes Simplex Virus Pathogenesis

• HSV causes lytic infections in most cells, persistent infections in lymphocytes/macrophages, and latent infections in neurons.
• Lesions in skin and mucous membranes caused by HSV-1 and HSV-2 are similar.
• The changes caused during primary and recurrent infection are also similar.
• Characteristic histopathologic changes include ballooning of infected cells and Cowdry type A intranuclear inclusion production.
• HSV can escape host defenses via formation of multinucleated giant cells and syncytia (fusion of cells).

Herpes Simplex Virus (HSV) Laboratory Diagnosis

• Cytology reveals characteristic CPEs (cytopathogenic effects).
• Tzank smears, Pap smears, or biopsy specimens are useful for cytology analysis.
• Giemsa staining can also be used to visualize CPEs (e.g., syncytia and Cowdry type A intranuclear inclusions).
• Methods like electron microscopy, immunofluorescence, PCR are available for diagnosing HSV infections.

Varicella-Zoster Virus (VZV)

• VZV causes chickenpox (varicella) and shingles (herpes zoster) which is the reactivation of latent VZV
• VZV is easily spread via respiration
• VZV replicates initially in the respiratory tract, then spreads to the skin causing crops of lesions
• VZV is susceptible to antiviral drugs similar to HSV.

Varicella-Zoster Virus (VZV): Pathogenesis

• VZV replicates in the respiratory tract, infecting epithelial cells, fibroblasts, T cells, and neurons.
• VZV creates syncytia (cell fusion) allowing for cell-to-cell spread.
• VZV spread can occur through viremia, causing crops of skin lesions.
• Cell-mediated immunity is crucial for VZV infection.

Varicella-Zoster Virus (VZV): Epidemiology

• VZV is extremely contagious, affecting >90% of susceptible persons.
• Transmission occurs primarily through respiratory droplets and skin vesicle contact.
• Risk groups include children (ages 5-9), teenagers/adults (more severe cases), immunocompromised individuals (disseminated disease), and newborns, who are at risk for serious infection.

Varicella-Zoster Virus (VZV): Clinical Features

• Varicella (chickenpox): acute, mostly symptomatic disease in children, with a typical maculopapular rash.
• Chicken pox-neonatal: occurs during maternal pregnancy, possible severe disease and high mortality
• Chicken pox-adults: more severe in adults. Interstitial pneumonia is the most common complication.

Varicella-Zoster Virus (VZV): Herpes Zoster (Shingles)

• Shingles (herpes zoster) is caused by reactivation of latent VZV.
• Occurs in 10-20% of infected individuals usually after the fourth decade of life.
• Unilateral vesicular eruption within a dermatome, often associated with severe pain.
• Reactivation can occur in immunocompromised individuals at any age.

Cytomegalovirus (CMV):

• CMV is part of the Beta-herpesvirinae subfamily.
• Lymphotropic
• Has the largest genome among human herpesviruses.
• The name comes from the cytomegalic cells (enlarged infected cells) observed during infection.
• Viral mRNAs are delivered directly into the cell to facilitate infection.
• CMV replicates only in human cells, very species-specific and cell-type-specific.
• CMV establishes latent infection.
• CMV generally causes subclinical infection in normal immunocompetent hosts.
• CMV infections usually become symptomatic only in immunocompromised individuals (e.g., AIDS patients).
• The condition may be severe and even life-threatening in immunodeficient individuals, pregnant women, and infants.

CMV: Pathogenesis

• CMV primarily replicates in epithelial and other cells.
• Latency occurs in T cells, macrophages, and other cells.
• Cell-mediated immunity plays a role in resolving/limiting/preventing acute infection.
• Antibody response is limited; immune compromise allows recurrence/severe presentation.

CMV: Epidemiology

• CMV transmission occurs through blood, organ transplants, secretions (urine, saliva, semen), and breast milk.
• Risk factors include newborns (through mother), organ transplant recipients, and immunocompromised individuals (e.g., AIDS patients) showing life-threatening disease

CMV: Diagnosis and Treatment:

• Characteristic cytomegalic cells (enlarged cells with an "owl's eye" intranuclear inclusion) and/or specific antibodies are used for diagnosis.
• Ganciclovir, foscarnet, cidofovir, and fomivirsen are used in treatments

Epstein-Barr Virus (EBV)

• EBV is a member of the Gamma herpes virinae subfamily.
• Hosts include both humans and some New World monkeys.
• EBV preferentially infects B cells, sometimes replicating in them, and some epithelial cells.
• EBV establishes latency in B cells.
• B cells are activated to enter the cell cycle, and a limited range of EBV genes are expressed.
• EBV causes heterophile antibody-positive infectious mononucleosis.
• EBV is associated with various cancers, including nasopharyngeal carcinoma and Burkitt's lymphoma (in immunocompromised individuals, young individuals living in malaria regions).
• EBV may also induce a variety of other benign to malignant tissue changes depending on infection and host status.

EBV: Epidemiology

• Transmission occurs via saliva.
• Risk includes children (asymptomatic), adolescents and adults (infectious mononucleosis in susceptible), immunocompromised (high risk for life-threatening neoplastic disease)

EBV: Pathogenesis

• Virus in saliva infects oral epithelia and spreads to B cells.
• Productive infection occurs in epithelial cells and B cells.
• EBV promotes B cell growth and immortalization.
• T cells limit B cell proliferation.
• Antibody plays a limited role in controlling infection.
• EBV latency occurs in memory B cells and reactivated after cell activation.

EBV: Infectious Mononucleosis

• Typical symptoms include enlarged lymph nodes and/or spleen as well as fever and sore throat .
• Atypical T cells (Downey cells) are visible.
• Diagnosis is via heterophile antibody testing, EBV IgM.

EBV: Burkitt Lymphoma

• BL is a jaw tumor, often associated with, though not always, infections in children who live in malaria endemic areas
• Frequent EBV presence.

EBV: Nasopharyngeal Carcinoma (NPC)

• Malignant tumor of squamous epithelium, most frequent in Southern China..
• EBV is strongly linked to NPC development.

EBV: Treatment and Prevention

• No established EBV vaccine yet available
• Treatment generally focuses on treating symptoms.
• Supportive care may be needed for some symptomatic diseases associated with EBV such as infectious mononucleosis.

Explore the diverse world of herpes viruses, focusing on their classification into subfamilies. This quiz covers the morphological features, replication processes, and transmission methods of alpha and beta herpesvirinae. Test your knowledge on the unique characteristics of these significant pathogens!