Herpesviruses Overview and Properties

Herpesviruses of Humans

• Herpesviruses are classified into subfamilies and genera.
• Simplexvirus includes Human Herpesvirus 1 (HHV-1) and Human Herpesvirus 2 (HHV-2).
• Varicellovirus includes Human Herpesvirus 3 (HHV-3), also known as Varicella-Zoster Virus (VZV).
• Betahepesvirinae includes Human Herpesvirus 5 (HHV-5), also known as Cytomegalovirus (CMV).
• Roseolovirus includes Human Herpesvirus 6 (HHV-6).
• Lymphocryptovirus includes Human Herpesvirus 4 (HHV-4), also known as Epstein-Barr Virus (EBV).

Properties of Herpesviridae

• Herpesviruses are spherical, enveloped virions, with a diameter of 120-200nm.
• They have an icosahedral capsid.
• They contain linear double-stranded DNA.
• Replication occurs in the nucleus.
• DNA replication and encapsulation occur in the nucleus.
• Herpesviruses establish latent infections, with their genome persisting in the nucleus of neurons or lymphocytes.
• Reactivation triggers replication and shedding of infectious virus.

Herpesvirus Particle

• Herpesvirus particles have identical morphology, making them indistinguishable under electron microscopy.

Replication

• HHV infection begins with virus attachment to cellular receptors.
• The virus penetrates the cell by fusion of the viral envelope with the plasma membrane.

Herpesviridae

• All herpesviruses can persist indefinitely in their host cells as an episome within the nucleus.
• In humans, herpesviruses of different subfamilies occupy specific ecological niches, particularly in different cell types.

Simplexvirus (HHV-1 & HHV-2)

• Transmission occurs via direct contact with infectious material.
• Orofacial herpes infections are often transmitted by kissing.
• Genital herpes infections result from direct contact, including genital-genital, oral-genital, and anal-genital contact.
• Herpes simplex infection can occur during asymptomatic virus shedding.
• Incubation period for herpes simplex is 2-12 days.

Gingivostomatitis

• Primary infection with HHV-1 often involves the mouth and/or throat.
• Young children may develop gingivostomatitis, characterized by vesicles on the mouth and gums that rupture to form ulcers.
• Following recovery, HHV-1 DNA persists in the trigeminal ganglion, leading to a high chance of recurrent attacks of herpes labialis (oral herpes).

Genital Herpes

• Primary genital herpes is typically caused by HHV-2, but HHV-1 is increasingly implicated.
• Genital herpes is commonly seen in young adults.
• Characteristic lesions include ulcerating vesicular lesions on the vulva, vagina, cervix, and perineum in females and the penis in males. Rectum and perianal regions can also be affected.

Lab Diagnosis

• Characteristic clinical presentations (e.g., recurrent herpes labialis) can aid diagnosis.
• Unclear-cut presentations may require additional tests, including tests for encephalitis, kerato-conjunctivitis, or genital herpes localised to the cervix.

Specimens for Diagnosis

• Vesicle fluid, cerebrospinal fluid (CSF), and swabs/scrapings from the genital tract, throat, eye, or skin can be collected for diagnosis.
• Isolation in cell culture and ELISA on CSF are methods.
• PCR is a preferred method for detecting HHV in CSF.

Chemotherapy

• Acyclovir and valacyclovir are common antiviral medications.
• Treatment of recurrent genital or oral herpes may not provide significant benefit.

Human Herpes Virus 3 (Varicella-Zoster Virus)

• HHV-3 causes two common diseases: chickenpox (varicella) and shingles (herpes zoster).
• Chickenpox typically occurs in childhood.
• Shingles is more common in older adults and immunocompromised individuals.
• VZV enters through inhalation and replicates in respiratory tract mucosa.

HHV-3 Pathogenesis

• Incubation period is 14 days.
• Virus spreads via lymphatics and blood, multiplying in mononuclear leukocytes and capillary endothelial cells.
• Skin rash results from viral multiplication in epithelial cells.
• Virus ascends sensory nerve axons and becomes latent in sensory ganglia.
• Primary infection is controlled by cellular immunity, leading to long-term immunity.

Human Herpes Virus-5

• Of all herpes viruses, HHV-5 (CMV) is the most frequent cause of morbidity and mortality among immunocompromised individuals.
• Infection is typically acquired subclinically in childhood through inhalation.
• Infected individuals carry the virus lifelong, intermittently shedding it in saliva, urine, semen, cervical secretions, and breast milk.
• During acute infection and reactivation, virus can be found in monocytes, polymorphs, and, to a lesser extent, lymphocytes.

HHV-5 Lab Diagnosis

• Viral culture is a slow method.
• HHV-5 DNA can be detected using polymerase chain reaction (PCR).

HHV-5 Treatment

• Ganciclovir and foscarnet are commonly used antiviral medications.
• These drugs are most effective for severe HHV-5 infections, such as pneumonia, chorioretinitis, and colitis.

Human Herpes Virus-4 (EBV)

• HHV-4's genome persists in B cells as a plasmid.
• Few viral genes are expressed, but expression of some leads to B-cell immortalization.
• Immortalized B cells produce B cell growth factor and monoclonal antibodies.
• The virus exists in two types, with Type A being most prevalent in Europe and the USA, often isolated from B lymphocytes.

HHV-4 Clinical Features

• EBV infection can result in infectious mononucleosis (glandular fever), with an incubation period of 4–7 weeks.
• Complications include neurologic disorders (e.g., Bell's palsy, meningitis, transverse myelitis).
• Other complications include nephritis and thrombocytopenia.
• EBV plays a role in certain cancers, such as Burkitt's lymphoma and nasopharyngeal carcinoma.

HHV-8

• HHV-8 is associated with Kaposi's sarcoma..
• transmission route is unknown although evidence leans towards sexual and solid organ transplants.
• HHV-8 infection plays a role in lesion development through infection of spindle and flat endothelial cells. This leads to cell proliferation/transformation.