Herpes Viruses: Introduction, Classification, Manifestations - PDF

HERPES VIRUSES By: Prof. MS Odimayo MB;BS, PGDE, FMCPath Consultant, Microbial Pathologist/Laboratory Physician Department of Microbial Pathology, Faculty of Basic Clinical Sciences, UNIMED, Ondo Ci...

HERPES VIRUSES By: Prof. MS Odimayo MB;BS, PGDE, FMCPath Consultant, Microbial Pathologist/Laboratory Physician Department of Microbial Pathology, Faculty of Basic Clinical Sciences, UNIMED, Ondo City, Nigeria  INTRODUCTION 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.  VIROLOGY 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  VIROLOGY Ctd Genome: they posses 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,  CLASSIFICATIONS classified into 3- subfamilies; α(3), β(3), γ(2) 1. Alphaherpesviruses 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. 2. Betaherpesviruses 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. 3. Gammaherpesviruses infect and become latent in lymphoid cells. e.g Epstein Bar Virus (EBV), & HHSV-8 (kaposi sarcoma-associated herpes virus).  CLASSIFICATIONS Ctd 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  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).  REPLICATION Ctd 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 & PATHOLOGY 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  PATHOGENESIS & BecausePATHOLOGY 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  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,  Herpes Virus and Common Diseases HSV-1 at the lip or mouth “cold sores”; HSV-2 can also be responsible HSV-2 genital herpes; HSV -1 can also be responsible HSV-1 Cold sore HSV-2 Genital Herpes  CLINICAL MANIFESTATIONS Ctd 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  CLINICAL MANIFESTATIONS CTD 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): caused by human herpesvirus 6 following T lymphocytes infection.  HSV Establishes Latent Infections Once infection has taken place HSV can remain dormant for months, years, lifetime Examples: – Shingles which can appear years after first chickepox infection (caused by varicella zoster, causes both chickenpox and shingles)  CLINICAL MANIFESTATIONS Human herpesvirus 7, also a T- CTD 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.  LABORATORY 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.  LABORATORY DIAGNOSIS Ctd 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. Experimental vaccines of various types are being developed.  Thank you