Herpes Simplex Virus

1. Herpes Simplex Virus Sidra Saeed FA08-BBS-015

2. CONTENTS • Symptoms • Diagnosis • Treatment Classification Discovery of HSV Types of HSV Viral Structure Complications Hosts of HSV Mode of Replication Virus Latency Modes of Transmission Immune Response against HSV

3. CLASSIFICATION Group: (dsDNA) Family: Herpesviridae Subfamily: Alphaherpesvirinae Genus: Simplexvirus Species: Herpes simplex virus 1 (HSV-1)Herpes simplex virus 2 (HSV-2)

4. How was the HSV Discovered HSV is an ancient disease with descriptions of orolabial herpes appearing in records from the fifth century BCE. In the 1736 Astruc (physician to King of France) identified Herpes as a cause of genital infection. Over the next 50 years many different strains of herpes were discovered. In 1893 intimate human-to-human transmission was identified. Finally neonatal HSV infection was identified in 1968.

5. Types of HSV The Type 1 virus causes cold sores. Most people get Type 1 infections during infancy or childhood. The Type 2 virus causes genital sores. Most people get Type 2 infections following sexual contact with an infected person. Both types can be differentiated by biologic, biochemical and antigenic properties

6. HSV Viral Structure Composed of a dsDNA (152kbp) nucleoprotein core Core is surrounded by an icosahedral protein capsid 100nm capsid is enclosed in an outer envelope consisting of at least 8 glycoproteins. The tegument is present between the capsid and the envelope Envelope spikes ~8 nm long The virus requires a moist environment for survival.

7. Complications • Meningitis:infection of the sheaths and membranes (meninges) covering the brain and the spinal cord. • Encephalitis:acute inflammation of the brain, commonly caused by a viral infection by insect bites or food and drink • Eczema herpetiform:widespread herpes across the skin) • Keratoconjunctivitis:Infection of the eye • Prolonged, severe infectionin immunosuppressed individuals • Pneumonia • Infection of the trachea • Keratitis-- Corneal infection, irritations, and inflammations

8. HSV Hosts • Humans • Simians • Cattle • Cats • Chickens Of these, only herpes virus simiae is harmful to us.

9. Modes of Replication • The viral envelop becomes incorporated in the host’s membrane

10. The nucleocapsiduncoats and releases the DNA into the nucleus.

11. In the nucleus the DNA circularizes, and the host’s enzymes begin to transcribe the first set of viral genes, known as early genes

12. The early mRNA molecules enter the cytoplasm, where they are translated into the early proteins.

13. The early proteins, in turn, enter the nucleus for viral DNA replication

14. At this point, the cell begins to transcribe late mRNA molecules

15. These mRNAs enter the cytoplasm for the translation of late proteins The late proteins include the capsid structural proteins, which enter the nucleus

16. The late proteins also include envelop proteins, which are produced in ER.

17. These envelop proteins become incorporated in the nuclear membrane

18. The viral DNA continues to replicate. During this later stage of replication concatemers of viral DNA form.

19. These copies are cut into individual genomes as they are packaged into capsids

20. At the nuclear membrane, capsid and the DNA bud off and become surrounded by membrane material with embedded membrane proteins

21. The virus passes through the ER and buds off this membrane before migrating to the plasma membrane

22. The virus fuses with the plasma membrane and is released from the cell.

23. Virus Latency

24. Virus Latency HSV is transmitted through the body on nerves or synapses to and from mucosal tissues • Vaccines and antiviral medicines can’t attack latent virus • Once infected, a person is infected for life. • Latency in mucosal surfaces is effective way to transmit • because of common mucosal contact

25. Modes of Transmission Direct skin-to-skin contact with the infected areas Sexual Intercourse Oral Sex Even though most skin on our bodies is too thick for the virus to penetrate, it can penetrate areas with mucous membranes such as the genitals, the mouth, the esophagus, the trachea, and even onto broken areas of skin anywhere

26. Immunology The constant battle between our body and invaders…

27. Immunology Both the cellular and humoral arms of the immune response are involved Interferon and natural killer cells are important in limiting the initial infection . Cytotoxic T cells and macrophages kill infected cells The humoral response (antibodies against surface glycoproteins) leads to neutralization. The virus can escape the immune system by coating itself with IgG via Fc receptors The virus can also spread from one cell to another without entering the extracellular space and coming in contact with humoral antibodies Cell-mediated responses are vital in controlling herpes infections.

28. Symptoms Mouth sores Genital lesions Blisters and/or ulcers Fever Enlargement of lymph nodes

29. Diagnosis of HSV The appearance of HSV is often so typical. The genital herpes sores may not be visible to the naked eye A viral PCR can be run on a swab of infected tissue. A blood test, can show if a person has been infected with HSV but cannot distinguish between type I and II. There are also newer blood tests that can tell whether a person has been infected with HSV I and/or II

30. Treatment of HSV • There is no vaccine that prevents this disease from occurring. • Oral anti-viral medications such as • acyclovir (Zovirax), • famciclovir (Famvir), • or valacyclovir (Valtrex) have been developed to effectively treat herpes infections.

31. Treatment of HSV • To keep from spreading the infection: • Keep the infected area clean and dry to prevent other infections from developing. • Try and avoid touching the sores. • Wash your hands after contact with the sores. • Avoid sexual contact from the time you first feel any symptoms until the sores are completely healed.

32. HUMAN PAPILLOMAVIRUS

33. DISCOVERY • Discovered by Dr Harald Zur Hausen in 1984 in German Cancer Research Centre. • Was found in the tumorous cells associated with cervical cancer patients. • A group of viruses containing almost 150 different types of viruses. • Double stranded DNA viruses.

34. BACKGROUND • Papilloma viruses are known to infect almost all mammallian and avian species having 100 types infecting humans • Specific types infect human skin and mucosal epithelium to cause papillomas or warts

35. Mucosal types of infection is found in persons having sexual contact with HPV infected women and homosexual males • Most of the infection caused by this are mostly cleared by the immune system before showing any symptoms

36. More than 5% of cancers worldwide are caused by infection from this virus • The most common sexually transmitted virus afflicting 50-80% population • Of the 100 known types; 40 infect the genital tracts • Of this 40; 15 cause cervical cancer in human females • Is histologically detected in women in the form of cervical cancer

37. REPLICATION • HPV infection is limited to the basal cells associated with stratified epithelium • These are the only tissues in which they can replicate • In case of any abrasion to epithelium it comes in contact with the basement membrane cells

38. Its infection process is slow taking 12-24 hours of transcription initiation • HPV virus does not show cytolytic activity • Rather the virus particles are released in the form of degeneration of desquamating cells

39. This virus can survive for many months without a host at low temperatures , so it can be spread if an infected person walks bare-foot

40. VIRAL REPLICATION • HPV has 6 early proteins(E1,E2,E3,E4,E5,E6) and 2 late proteins (L1,L2) • Before integrating in host genome • High levels of E1 & E2 • E2 repress E6/E7 expression

42. After integrating in host • E2 function disrupted • Prevents repression of E6/E7

43. ONCOGENES • Role of E6 & E7 proteins in cancer • E6 inactivates p53 TSP whereas E7 inactivates pRb TSP • These proteins modify the host cell cycle • to keep differentiating the keratinocytes • helps in the amplification of viral genome replication

44. ROLE of E6 Protein • E6 forms association with E6 associated protein of host • Ubiquitinate the p53 protein • cause proteosomal degradation of p53

45. ROLE OF E7 PROTEIN • E7 acts as primary transforming protein • Competes for retinoloblastoma protein binding • Freeing the transcription factor E2f to transactivate its target pushing cell cycle forward

46. LATE PROTEINS L1&L2 • These are structural proteins that encapsidate the viral genome • Once the genome is encapsidated it undergoes the assembly/maturation event

47. Stabilizes the virions • Increases viral specific infectivity • Virions can then be sloughed off as squames from host epithelium and viral life cycle continues

48. TRANSMISSION • Prenatal • Genital HPV are usually transmitted from mother to newborn • Perinatal • Perinatal transmision of HPV type 6 and 11 causes onset of juvenile-onset recurrent respiratory papilllomatosis(JORRP) • About 2 cases in 100,000 births in U.S

49. Genital • transmission is from infected partner during sexual contact • it can not be prevented even using condoms • because some of the infected region is exposed to the body of the partner

50. SYMPTOMS • COMMON WARTS • rough, raised bumps that usually occur on the hands, fingers or around fingernails.