HERPES

Presented by-Rohit.

INTRODUCTION• Herpes is a viral disease caused by HSV1 and HSV2.

• HSV1 causes oral herpes and HSV2 cause genetical herpies.

• HSV1 is highly contagious which is acquired orally and cause cold sores on mouth lips or any other part of body exept genetals which can be easily passed from person to person by direct skin to skin contact.

• HSV2 is usually transmitted by having sex and affects the genital area,that’s why it is called STD(Sexually Transmitted Disease).

• HSV infection typically results in lifelong latent infection that periodically give rise to clinical outbreaks, expressed as lesions. Once you have it, there are chances that it will attack again and again.

• After completion of infection cycle the viruses are transported along sensory nerves to the sensory nerve cell bodies, where they become latent and reside lifelong.

• HSV is one of the most difficult viruses to control because HSV1 when transmitted to genetical area causes genetical herpes and HSV2 when transmitted to mouth can cause oral herpes. In short the herpes virus changes its mode of action according to area where it is transmitted.

HERPES SIMPLEX 1 HERPES SIMPLEX 2

STRUCTURE OF VIRUS

GENOME CHARACTERSTICS

• Herpes virus genomes range in length from 120 to 230 kbp with base composition from 31% to 75% G+C content and contain 60 to 120 genes.

• Herpesviruses can use both the host's transcription machinery and DNA repair enzymes to support a large genome with complex arrays of genes.

• Herpes virus genes, like the genes of their eukaryotic hosts, are not arranged in operons and in most cases have individual promoters.

Biological Properties• The synthesis of viral genomes and assembly of capsids occurs

in the nucleus.• Productive viral infection is accompanied by inevitable cell

destruction. • Herpesviruses express a large number of enzymes involved in

metabolism • Herpesviruses are able to establish and maintain a latent state

in their host and reactivate following cellular stress. Latency involves stable maintanence of the viral genome in the nucleus with limited expression of a small subset of viral genes.

Strategies for Success

• The virion invades the host cell, turning off host protein synthesis and releasing viral DNA into the nucleus, where replication and virion production start immediately.

• Second tactics include inhibiting splicing of mRNA, blocking presentation of antigenic peptides on the cell surface and blocking the apoptosis (cell death) induced by viral gene expression.

• Third important strategy shared by herpesviruses is their ability to hide their bare

Signs and symptomsHSV1

• Small, painful blisters filled with fluid around any upper body part or legs.

• Fever.

• Sore throat.

• Swollen lymph nodes in neck.

• Tingling or burning around the face.

HSV2

• Tingling sensation in the genitalia, buttocks, and thighs.

• Small red blisters or open sores on genitals

• Fever, muscle aches.

• Painful urination and vaginal discharge.

• Swollen lymph glands.

Risk factors

• Pregnant women who are infected with herpes simplex virus 2 have a higher risk for miscarriage, premature labor and retarded fetal growth.

• May cause permanent Effects on the Brain and Central Nervous System.

• May cause permanent blindness if spread to eye.

• Herpes simplex in any patient with a seriously compromised immune system can cause serious and even life-threatening complications including Inflammation of the esophagus and brain, Liver damage, destruction of adrenel glands etc.

Treatment• There is no cure for herpes, so the goals of treatment are to

reduce the number of outbreaks and to lessen symptoms and make the virus dormant.

• In normal person the blisters goes away naturally but in case immunocompromized patients and pregnant women, special treatment is needed.

• Antiviral medicines like Acyclovir, Valtrex etc help shorten the length of a herpes outbreak and cut down on recurring outbreaks by inhibiting replication process of the virus.

Mode of action of drugs.

valtrex aciclovir

monophosphate form

aciclo-GTPViral DNA pol

esterases

hepatic first-pass metabolism

thymidine

kinase

cellular kinases

phosphorylation

inhibition

Valtrex

Acyclovir

Drug targetsRiboneucleotide reductase

• Herpes simplex viruses encode their own RR.

• Converts ribonucleoside diphosphates to the corresponding deoxyribonucleotides required for viral DNA synthesis.

• First anti-RR products to be identified belonged to the thiosemicarbazone family.

• These peptides inhibit HSV RR activity in vitro by inducing dissociation of the two subunits [58-60] and suppress the replication of HSV-1, HSV-2.

Helicase-Primase

• The helicase–primase complex comprises three viral proteins encoded by the UL5, UL8 and UL52 gene products.

• It unwinds double-stranded viral DNA and generates primers for DNA synthesis by the viral DNA pol.

• The helicase primase complex plays an essential role in HSV DNA replication and thus constitutes an excellent target for antiviral therapy.

Polyamine pathway• Potential cellular target.

• A recent report has demonstrated that the polyamine biosynthetic pathway remains active in HSV.

• Two key enzymes of this pathway, S-adenosylmethionine decarboxylase (SAMDC) and ornithine decarboxylase,is upregulated.

• The use of methylglyoxal bis,(specific SAMDC inhibitor), reveals that SAMDC activity is required for HSV-1 and HSV-2 replication in cell culture.(in vitro).