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Dr. Jing Qian Dept. of Medical Microbiology and Parasitology Medical school, Zhejiang university

Lectures for biomedical students. Viruses of Herpesviridae 疱疹病毒. Dr. Jing Qian Dept. of Medical Microbiology and Parasitology Medical school, Zhejiang university Email: jingqian@zju.edu.cn 2014.6.3. Herpesvirus. Introduction. Herpes virus. Greek word herpein

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Dr. Jing Qian Dept. of Medical Microbiology and Parasitology Medical school, Zhejiang university

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  1. Lectures for biomedical students Viruses of Herpesviridae 疱疹病毒 Dr. Jing Qian Dept. of Medical Microbiology and Parasitology Medical school, Zhejiang university Email: jingqian@zju.edu.cn 2014.6.3

  2. Herpesvirus Introduction

  3. Herpesvirus • Greek word • herpein • ----to creep

  4. Herpesvirus Sarcoma Variable

  5. Herpesvirus Sarcoma

  6. Human Herpesviruses Latent infection The Virus persists in an occult, or cryptic, from most of the time. There will be intermittent flare-ups of clinical disease, Infectious virus can be recovered during flare-ups. Latent virus infections typically persist for the entire life of the host. Sarcoma Variable

  7. Human Herpesviruses (HHV) H Sarcoma Variable

  8. Common features • Herpesviruses have large, enveloped icosadeltahedral capsidscontaining double-stranded DNA genomes. • Herpesviruses encode many proteins that manipulate操纵 the host cell and immune response. • Herpesviruses encode enzymes (DNA polymerase) that promote viral DNA replication and that are good targets for antiviral drugs. • DNA replication and capsid assembly occurs in the nucleus. • Virus is released by exocytosis, cell lysis, and through cell-cell bridges. • Herpesviruses can cause lytic, persistent, latent, and, for Epstein-Barr virus, immortalizing infections. • Herpesviruses are ubiquitous. • Cell-mediated immunity is required for control.

  9. Viral genes essential for viral replication in culture

  10. Subfamily

  11. Herpesvirus Herpes simplex Virus (HSV) • HSV-1 (HHV-1) • HSV-2 (HHV-2)

  12. Subfamily

  13. infectant reservoir patients and carriers transmitted ways • HSV-1: contact • HSV-2: sexually • vertical transmission

  14. Pathogenesis • primary and recurrent infections • cytolytic infection • latent infection • latently infected ganglia in a non-replicating state • trigeminal ganglia三叉神经节(HSV-1); sacral ganglia骶神经节(HSV-2)

  15. Triggers of HSV Recurrences Primary herpetic gingivostomatitis 原发性疱疹性龈口炎 Cold sore of recurrent herpes labialis 复发性唇泡疹引起的感冒疮

  16. Clinical syndromes • Oropharyngeal disease/ keratoconjunctivitis • HSV-1 (usually) • 6m - 2y • genital herpes • HSV-2 (usually) • herpes encephalitis • HSV-1 (90%) • neonatal herpes • HSV-2 (75%) A baby girl is shown in Slide 22. I took this picture postmortem; the baby was 28 weeks gestation and died of disseminated herpes, neonatal herpes simplex encephalitis. You can see crusted lesions all over the baby's face. http://www.medscape.org/viewarticle/528947_5

  17. Diagnosis multinucleate cell with dark staining inclusions

  18. Diagnosis Plaque Assay

  19. Diagnosis

  20. Diagnosis Treatment • acyclovir • Patients with genital herpes should avoid intercourse when they have the prodromal itching symptoms or an active lesion.

  21. Herpesvirus Varicella-Zoster Virus (HHV-3)

  22. Subfamily

  23. Mechanism of spread of varicella-zoster virus (VZV) within the body means of spreading: respiratory tract and close contact primary target cells mucoepithelial cells place of latency neuron

  24. Pathogenesis and clinical syndromes chicken-pox (Varicella) Each spot starts as a 2-4 mm diameter red papule which develops an irregular outline (rose petal) as a small vesicle appears on the surface. This 'dew drop on a rose petal' appearance is very characteristic of chickenpox.

  25. Pathogenesis and clinical syndromes ganglia

  26. Pathogenesis and clinical syndromes Shingles

  27. Pathogenesis and clinical syndromes The virus may then be reactivated under stress or with immune suppression.

  28. Congenital Varicella syndrome • caused by infection in utero during the first trimester • leads to scarring of the skin of the limbs, damage to the lens, retina and brain and microphthalmia • or at birth from infected mother • severe skin infection

  29. Treatment acyclovir Vaccine live attenuated vaccine virus

  30. Herpesvirus Cytomegalovirus (HHV5)

  31. Subfamily

  32. Sources of Cytomegalovirus Infection

  33. Outcomes of cytomegalovirus (CMV)infections The outcome depends very heavily on the immune status of the patient

  34. LABORATORY DIAGNOSIS Histology H&E stain of lung section showing nuclear inclusions with the appearance of an "owl's eye". The inclusion is surrounded by a clear halo that extends to the nuclear membrane.  CMV infection can occur without the typical cytomegalic cells. Immune and DNA Probe Techniques Culture Serology

  35. Treatment Ganciclovir Foscarnet Acyclovir is not effective

  36. Herpesvirus Epstein- Barr Virus (HHV4)

  37. Subfamily

  38. potential outcomesofEBV infection • replicate in B cells or epithelial cells permissive for EBV replication. • cause latent infection of B cells in the presence of competent T cells. • stimulate and immortalize B cells.

  39. Diseases related to EBV infection • Burkitt's lymphoma (Africa) large multinucleated cells

  40. Diseases related to EBV infection • Burkitt's lymphoma (Africa) • nasopharyngeal carcinoma • (Guangdong, China; areas in southeast Asia)

  41. Diseases related to EBV infection • Burkitt's lymphoma (Africa) • nasopharyngeal carcinoma (Guangdong, China; areas in southeast Asia) • infectious mononucleosis (Europe, North America) Atypical T-cell (Downey cell) characteristic of infectious mononucleosis. The cells have a more basophilic and vacuolated cytoplasm than normal lymphocytes, and the nucleus may be oval, kidney shaped, or lobulated. The cell margin may seem to be indented by neighboring red blood cells. A conjunctival hemorrhage of the right eye of this patient with infectious mononucleosis.

  42. Treatment and prevention • no drugs available to treat Epstein-Barr virus. • A vaccine is being developed.

  43. Retroviridae

  44. RETROVIRIDAE IMPORTANT ASPECTS • Contain a helical nucleoprotein complex inside an icosahedral capsid which is enveloped • Genomic RNA undergoes reverse transcription • Genome (as DNA) integrated into host cellular DNA • Some members carry oncogenes • HIV-1, the cause of AIDS

  45. Human Immunodeficiency Virus 1+2 Acquired ImmunoDefiency Syndromes HIV AIDS Global situation

  46. REPORT ON THE GLOBAL AIDS EPIDEMIC (UNAIDS) • UNAIDS: joint united nations programme on HIV/AIDS

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