1. Latent Viruses

2.  Herpes Viruses are a leading cause of human viral diseases, second only to influenza and cold viruses.  Are capable of causing overt disease or remaining silent for many years only to be reactivated.  Name Herpes comes from the Latin herpes which, in turn, comes from the Greek word herpein which means to creep.

3. DNA double stranded virus, linear 125-250 Kb long, relatively big Enveloped Virion size 200 nm, relatively big 9 HSVs, Ex. Varicella, EBV, CMV Diseases: Chickenbox, Mononucleosis, Hepatitis, Encephalitis Recurrent eye, mouth and genital lesions Chickenpox, Varicella Zoster

4.  There are 25 families in the Herpeotoviridae but only 6 of them infect man with any regularity. Herpes Simplex virus Type 1 (HSV-1) Herpes Simplex virus Type 2 (HSV-2) Epstein Barr virus (EBV) Cytomegalovirus (CMV) Varicella Zoster virus (VZV) Human Herpes virus 6 Human Herpes virus 8

5.  These are very large viruses and their genome encodes at least 80 proteins.  Half are not directly involved in the virus structure.  Almost any human cell type can be affected by HSV.

7.  HSV-1 and 2 infections are life-long.  The virus is found in the lesions on the skin but can be present in body fluids including saliva and vaginal secretions.  As a result of poor hygiene in underdeveloped countries, HSV-1 antibodies are found in more than 90% of children.

8.  HSV-2 is normally spread sexually and is found in the anus, rectum and upper alimentary tract as well as the genital area.  An infant can be infected at birth by a genitally-infected mother.  The infant can also be infected in utero if the mother’s infection spreads.  Because of the infant’s underdeveloped immune system, the resulting infection can be very severe and sometimes be deadly.

9.  Oral Herpes - Cold sores  Herpetic gingiovostomatitis, the infection, often initially on the lips spreads to all parts of the mouth and pharynx.

10.  Everybody knows chickenpox and likely you experienced the disease as a child, can be dangerous when exposed to it in adulthood  Another common ailment is lip and mouth “cold sores”  Genital Herpes lesions caused by HSV, sexually transmitted  HSV-1 cold sores (mild but annoying diseases)  HSV-2 genital herpes  Varicella zoster: chickenpox  However the Herpes family is huge, over 100 members HSV-1 Cold soreHSV-2 Genital Herpes

11.  Eczema Herpeticum  This is found in children with active eczema.  The virus can spread to other organs such as the liver and adrenals.

12.  Genital Herpes  Is usually the result of HSV-2.  Primary infection is often asymptomatic but many painful lesions can be developed on the shaft of the penis and vulva, vagina, cervix and perianal region of women.

14.  In both sexes, the urethra can be involved.  Genital Herpes infections can be accompanied by a variety of symptoms including fever, myalgia, glandular inflammation of the groin area (inguinal).  Some patients have only infrequent recurrences but others experience recurrences as often as every 14-21 days.

15.  Once infection has taken place HSV can remain dormant for months, years, lifetime  Cell types that HSV can infect and remain dormant  Neurons, B-cells and T-cells  Examples:  Shingles which can appear years after first chickepox infection (caused by varicella zoster, causes both chickenpox and shingles)  Genital Herpes outbreaks

16.  Enclosed in an envelope  Capsid has icosahedral structure  Capsid is bilayered  Constructed from 6 proteins  VP5 is the main one  Envelope contains at least 10 different glycoproteins gB-gM  Envelope also contains non-glycosylated proteins

17.  gB and gC bind to host glycoproteins with heparan sulfate moieties (repeating dissacharide: glucoronic and n-acetyl glucosamine)  Following gB and gC is gD which binds to nectin1D  OR HVEM (herpes virus entry mediator)  Fusion occurs between viral envelope and host membrane  Nucleocapsid is released into cytosol OR in acidified endosomes  Transport to nuclear envelope occurs via  T and capsid interaction  DNA is released into nucleus  Capsid disintegrates http://www.dipartimentobiologia.it/doctoraltraining/campadelli. htm

19.  Cells may be obtained from the base of the lesion (called a Tzank smear) and histochemistry performed.  These can be seen in the smears as multinucleated giant cells and contain Cowdry type A inclusion bodies.

21.  The cells can also be stained with specific antibodies in an immunofluorescence test.  It can also be detected by viral DNA by in situ hybridization.  Type-specific antibodies can distinguish between HSV-1 and HSV-2.

22.  Acyclovir  A Safe and extremely well-tolerated drug.  More than 35 million patients have been consistent and reassuring.  Some authorities have proposed making acyclovir available as a non-prescription drug.  Adverse effects, usually mild, include nausea, vomiting, rash and headache.

23.  Valacyclovir  New antiviral agent  Is the 1-valine ester prodrug of acyclovir.  It has an oral bioavailability three to five times greater than that of acyclovir.  Several large trials have shown that it is safe and well tolerated.

24.  Famciclovir  Another new antiviral medication  Is the oral form of penciclovir, a purine analog similar to acyclovir.  Oral bioavailability is 77% and the drug is quickly converted to its active form.  Famciclovir’s intracellular half-life is 10 times longer than acyclovir’s.  Dosing less frequently than twice daily is not recommended.