L4 Herpes MLS Diploma - Tagged

General Background

  • Herpes viruses are significant human pathogens characterized as large enveloped DNA viruses, acquiring their envelope from the nuclear membrane.

  • They are known for their ability to produce latent (asymptomatic lifelong) and recurrent (reactivated) infections.

  • These viruses are widespread, affecting a majority of the human population.

  • Herpes viruses can induce various effects in host cells:

    • Lytic infections: kill the host cell

    • Persistent infections: continuously produce the virus, usually asymptomatic

    • Latent infections: minimal viral activity

    • Immortalized infections: notably seen in Epstein-Barr virus (EBV)

  • Their genomes encode several proteins and enzymes crucial for viral replication and immune evasion, making them viable targets for antiviral therapy.

Classification of Human Herpes Viruses

  • Human herpes viruses are classified based on their viral characteristics, including:

    • Genome structure

    • Tissue tropism

    • Cytopathology effects

    • Site of latent infection

Structure of Herpes Viruses

  • Composed of:

    • Envelope proteins (gB-gN)

    • Lipid envelope

    • Tegument or Matrix

    • DNA Nucleocapsid

  • Structure is large, enveloped, and has an icosahedral capsid.

Human Herpesvirus Genome

  • The herpes virus genome consists of double-stranded linear DNA (~150 Kb).

  • There is little DNA homology between various herpes viruses, except between HSV-1 and HSV-2, which are very similar.

Life Cycle of Herpes Viruses

  • The life cycle involves several steps:

    1. Attachment and Fusion: Viral envelope merges with the host plasma membrane allowing capsid entry.

    2. Uncoating: Delivery of viral DNA into the nucleus.

    3. Viral Gene Expression: Transcription and translation of viral proteins.

    4. DNA Replication: Producing more viral DNA.

    5. Viral Assembly: Formation of new virus particles.

    6. Budding and Release: The virus acquires its envelope and is released, either through lysis or exocytosis.

  • Latency occurs with minimal viral production, particularly in neurons.

Herpes Simplex Viruses (HSV)

  • There are two types: HSV-1 and HSV-2, both prevalent in the population (approximately 65% have HSV-1 and 15% have HSV-2 in the US).

  • HSV-1 typically affects areas above the waist (e.g., oral), while HSV-2 is associated with below-the-waist infections (e.g., genital).

  • Both types are capable of causing lytic infections in epithelial cells and establishing latent infections in neurons.

Diseases Caused by HSV-1 and HSV-2

  • Herpes Labialis: Commonly caused by HSV-1 (often referred to as cold sores).

  • Genital Herpes: More frequently caused by HSV-2 but can also be due to HSV-1.

  • Herpes Encephalitis: Typically caused by HSV-1, leading to severe morbidity and mortality.

  • Neonatal HSV: Passed from mother during delivery, potentially leading to severe outcomes due to the immature immune system.

Latency of HSV

  • HSV-1 establishes latency in trigeminal ganglia, while HSV-2 affects sacral ganglia.

  • Reactivations may occur asymptomatically, with viral shedding.

Triggers of HSV Recurrences

  • Common triggers for reactivation include:

    • Ultraviolet light

    • Fever

    • Stress (emotional and physical)

    • Menstruation

    • Immunosuppression

Laboratory Diagnosis of HSV Infections

  • Methods include:

    • Direct microscopic examination (Tzanck smear)

    • Cell culture

    • PCR for HSV DNA detection

HSV Antivirals

  • Antiviral treatments include:

    • Acyclovir, Valacyclovir, Famciclovir: Guanosine analogs that inhibit viral DNA polymerase.

    • Foscarnet: An inhibitor of viral DNA/RNA polymerase used for acyclovir-resistant strains.

    • Cidofovir: Similar to foscarnet, effective for resistant HSV.

  • These medications can reduce severity of infections but do not cure latent infections.

Varicella Zoster Virus (VZV)

  • Primary disease manifests as chicken pox; reactivation causes shingles.

  • Infection occurs via respiratory droplet, with a characteristic rash developing after a few days.

  • Post-herpetic neuralgia is a common complication following shingles.

Epstein-Barr Virus (EBV)

  • Known for inducing B cell proliferation and latency in memory B cells.

  • Symptoms can range from subclinical to infectious mononucleosis (kissing disease).

  • Diagnosis often involves detecting atypical lymphocytes and specific viral antibodies.

Cytomegalovirus (CMV)

  • Recognized for its larger genome and immune evasion capabilities, often affecting immunocompromised patients.

  • CMV can be transmitted through saliva, genital fluids, and vertically from mother to child.

  • Symptoms vary significantly based on the individual's immune status, with serious implications for neonates.