HERPES VIRUSES Flashcards
(8 cards)
What is the herpes virus?
The name herpes comes from the Latin herpes (Greek word herpein) meanings to creep.
This reflects the creeping or spreading nature of the skin lesions caused by many herpesviruses
• Herpes viruses are a leading cause of human viral disease, second only to influenza and cold viruses.
• They are characterised by active and latent diseases e.g Chickenpox/shingles.
• Once infected is for life!
Virology of herpes
Envelope: Herpes viruses are enveloped viruses. Envelope is acquired during budding from nuclear membrane.
•Tegument: Between the envelope and the capsid is the tegument which contains virally-encoded proteins and enzymes involved in the initiation of replication
• Capsid: They are doughnut shaped with icosahedral nucleocapsid.
• Genome: they possess double stranded DNA. The size of the genomes differs with cytomegalovirus having the largest genome
• Outstanding characteristics include: Establishment of latent infections, indefinite Persistence in infected hosts, Frequent reactivation in immunosuppressed hosts,
•Some are cancer-causing: e.g Epstein Barr virus ( Burkitt’s lymphoma), HHV-8 (kaposi)
Classification
Classified into 3- subfamilies; α(3), β(3), γ(2)
- Alpha herpes viruses are fast-growing, cytolytic viruses that tend to establish latent infections in neurons.
Human herpes simplex virus-1 (HHSV-1), HHSV-2, & varicella zoster virus.
- Beta herpes viruses are slow-growing and may be cytomegalic (massive enlargements of infected cells) and become latent in secretory glands and kidneys e.g Cytomegalovirus, human herpesviruses 6 and 7.
- Gamma herpes viruses infect and become latent in lymphoid cells. e.g Epstein Bar Virus (EBV), & HHSV-8 (kaposi sarcoma-associated herpes virus).
•1. Herpes simplex virus Type 1 (HSV-1)- α
•2. Herpes simplex virus Type 2 (HSV-2)- α
•3. Varicella Zoster Virus (VZV)-α
•4. Cytomegalovirus (CMV)- β
•6. Human herpes virus 6 (exanthum subitum or roseola infantum)- β
•7. Human herpes virus 7- β
•4. Epstein Barr virus (EBV)- ᴕ
•8. Human herpes virus 8 (Kaposi’s sarcoma-associate herpes virus) -ᴕ
Replication
• The virus enters the cell by fusion with the cell membrane after binding to specific cellular receptors e.g heparan sulfate via envelope glycoproteins.
• After fusion, the capsid enters the nucleus where uncoating occurs; the DNA becomes associated with the nucleus.
• Expression of the viral genome is tightly regulated and sequentially ordered in a cascade fashion.
• Expression of Immediate-early genes yields “alpha” proteins which are translated into “beta” proteins, then viral ‘DNA’ replication and production of late transcripts (“gamma” proteins).
• α and β proteins are mainly enzymes or DNA-binding proteins; while γ are structural proteins.
• Maturation occurs by budding of through nuclear membrane. Enveloped virus particles are transported by vesicular movement to cell surface.
• Cells productively infected are invariably killed. Host molecular synthesis is shut off early in infection
• Cellular DNA and protein synthesis virtually stop as viral replication begins.
Pathogenesis and pathology
Where can HSV-1 and HSV-2 be found?
• HSV is transmitted by contact with an individual excreting the virus or droplets via mucosal surfaces or broken skin.
• HSV-1 infections are usually limited to the oropharynx while HSV-2 is by genital routes.
• Viral replication occurs first at the site of infection, invades local nerve endings, then transported by retrograde axonal flow to dorsal root ganglia, where, after further replication, latency is established.
• Because HSV causes cytolytic infections, pathologic changes are due to necrosis of infected cells and inflammatory response.
• Lesions induced in the skin and mucous membranes by HSV-1 and HSV-2 resemble those of varicella-zoster virus.
• Changes induced by HSV are similar for primary and recurrent infections but vary in degree, reflecting the extent of viral cytopathology.
Manifestations
• Primary HSV infections may be asymptomatic.
• Rarely, systemic disease develops, involving multiple organs in immunocompromised host.
• Latent infections: occurs in nonreplicating state (Oropharyngeal HSV-1 in trigeminal ganglia; genital HSV-2 in sacral ganglia).
• Provocative stimuli e.g fever, emotional stress e.t.c can reactivate virus from the latent state, manifest as cold sores (fever blisters) near the lip in more over 80% of humans
• Keratoconjunctivitis of HSV-1 infections may occur in the eye, causing keratoconjunctivitis.
• Oropharyngeal disease: Involves buccal and gingival mucosa of the mouth in children of 1-5 years. Symptoms include fever, sore throat, vesicular and ulcerative lesions, gingivitis.
• Pharyngitis and tonsillitis may occur in adult
• Neonatal Herpes: HSV infection of the newborn may be acquired in utero, during birth, or after birth. may be very severe.
• Chickenpox (varicella): caused by Varicella-zoster virus on primary infection and zoster (shingles) on reactivation of latent infection.
• Infectious mononucleosis: caused by Epstein-Barr virus follwing replication in epithelial cells of the oropharynx and parotid gland and establishes latent infections in lymphocytes.
• Cytomegalic inclusion disease may occur In newborns, CMV is an important cause of congenital defects and mental retardation.
• Exanthem subitum (roseola infantum):
- Human herpesvirus 7, also a T-lymphotropic virus, has not yet been linked to any specific disease.
• Malignancy: Epstein-Barr virus (Burkitt’s lymphoma, nasopharyngeal carcinoma, and other lymphomas); Human herpesvirus 8 or Kaposi’s sarcoma-associated herpesvirus (Kaposi’s sarcoma).
• Encephalitis: severe encephalitis may be caused especially by HSV-1 with a high mortality rate, residual neurologic defects.
Lab diagnosis
• Cytopathology: staining of scrapings obtained from the base of a vesicle (eg, with Giemsa’s stain); the presence of multinucleated giant cells indicates that herpesvirus (HSV-1, HSV-2, or varicella-zoster) is present,
• Virus isolation: during primary infection and during asymptomatic periods. Therefore, the isolation of HSV is not in itself sufficient evidence to indicate that the virus is the causative agent of a disease under investigation.
• Polymerase Chain Reaction (PCR)
• Serology: Antibodies appear in 4–7 days after infection and reach a peak in 2–4 weeks. They persist with minor fluctuations for the life of the host. The use of HSV type-specific antibodies, available in some research laboratories, allows more meaningful serologic tests.
Treatment and prevention
• Antiviral drugs including acyclovir, valacyclovir, and vidarabine. Acyclovir is currently the standard therapy. All are inhibitors of viral DNA synthesis.
• The drugs may suppress clinical manifestations, shorten time to healing, and reduce recurrences of genital herpes. However, HSV remains latent in sensory ganglia.
• Newborns and persons with eczema should be protected from exposure to persons with active herpetic lesions
