1. Herpesviruses Herpes simplex I & II (cold sores, genital herpes)
D- virology
Herpesviruses
Herpes simplex I & II (cold sores, genital herpes)
Varicella zoster (chicken pox, shingles)
Cytomegalovirus (microcephaly, infectious mono)
Epstein-Barr virus (mononucleosis, Burkitt’s lymphoma)
Human herpesvirus 6 & 7 (Roseola)
Human herpesvirus 8 (Kaposi’s sarcoma)

2. Cold Sores

3. Zoster

6. Roseola

8. Human Herpesviruses Virus Subfamily Disease Site of Latency
Herpes Simplex Virus I α Orofacial lesions Sensory Nerve Ganglia
Herpes Simplex Virus II α Genital lesions Sensory Nerve Ganglia
Varicella Zoster Virus α Chicken Pox Sensory Nerve Ganglia
Recurs as Shingles
Cytomegalovirus β Microcephaly/Mono Lymphocytes
Human Herpesvirus 6 β Roseola Infantum CD4 T cells
Human Herpesvirus 7 β Roseola Infantum CD4T cells
Epstein-Barr Virus γ Infectious Mono B lymphocytes, salivary
Human Herpesvirus 8 γ Kaposi’s Sarcoma Kaposi’s Sarcoma Tissue

10. Herpes Simplex Virus
Prototype of group

11. Virion stabiliy Enveloped virus Sensitive to dessication
Easily inactivated by detergents and lipid solvents

12. Virion structure Enveloped, spherical virion
Icsoahedral capsid nm
>12 virally encoded glycoproteins
Tegument proteins

13. Genome structure Linear double-stranded DNA 120 - 230 kb
Genetic complexity -- isomers

14. Genome structure Linear double-stranded DNA 120 - 230 kb
Genetic complexity
# of genes

15. Replication Penetration by fusion with plasma membrane
Nuclear site of replication
80 or so viral proteins are expressed in regulated fashion:
IE - immediate early
E - Early
L - Late
Capsids assemble in nucleus and bud through nuclear membrame

17. Life-long Latency

20. Three manifestations of HSV latency
Key Feature: there is a wide spectrum of clinical presentations
Some individuals (5 - 10%) have frequent clinical reactivation
Most individuals reactivation is clinically asymptomatic
In ALL cases, virus is shed

21. Transmission of HSV-1 and HSV-2
Skin to skin contact
The virus does not penetrate intact skin
Mild abrasion or chapping of skin can allow infection

22. Tissue tropism of HSV-1 and HSV-2
Causes 95% of orofacial herpes (remainder caused by HSV-2)
Causes % of primary genital herpes (but seldom recurs there)
HSV-2:
Causes primary and recurrent genital herpes infections
May cause primary oral herpes but, like HSV-1 in genital area, it seldom recurs there

28. Eczema/Herpes

31. Herpes Simplex Virus type 2
Infects the genital tract
Is sexually transmitted
Complicates childbirth

34. Diagnosis of Herpes Simplex Virus Infections:
Viral Culture
Tzanck prep
Culture with monoclonal antibody staining
Serology
Polymerase chain reaction (PCR)

36. Spectrum of HSV recurrence
Asymptomatic shedding
Shedding with clinically apparent lesions

37. A study of HSV-2 recurrence in women

38. Asymptomatic Shedding of HSV
Occurs in both HSV-1 and HSV-2
The only form of shedding in 1/2 to 2/3 of infected patients
Involves low amounts of virus
Accounts for most transmissions to infected contacts and neonates
Is not completely suppressed by acyclovir

39. 2/3

40. 2/3
of the acquisitions of genital herpes come from clinically asymptomatic partners

41. Alpha Herpesviruses Site of Latency
Herpes Simplex Virus type 1 Sensory neurons
Herpes Simplex Virus type 2 Sensory neurons
Varicella Zoster Virus Sensory neurons
Beta Herpesviruses
Cytomegalovirus Lymphocytes
Human Herpesvirus 6 CD4 T cells
Human Herpesvirus 7 CD4 T cells
Gamma Herpesviruses
Epstein-Barr Virus B lymphocytes
Human Herpesvirus 8 Sarcoma tissue

42. Two Unique Features of VZV:
Airborne spread or skin to skin contact
More severe infection if primary infection occurs as an adult

43. Complications of Varicella
Reye’s Syndrome
Bacterial Superinfection of lesions (more common in younger patients)
Varicella pneumonia
Neonatal varicella -- disseminated, 30% mortality

44. Varicella Pneumonia Age Fatalities per 100,000 <1 6.23 1 - 14 0.75
<

45. Varicella patients at risk
ADULTS
PREGNANCY (3rd trimester)
IMMUNOCOMPROMISED
The mortality rate for varicella pneumonia in leukemic children receiving chemotherapy is 1,000 times higher than in healthy children.
Note: Children with isolated agammaglobulinemia are not at risk!

48. Neonatal Varicella

51. Zoster

52. Varicella Vaccine Prevents 40 - 70% of chickenpox occurrence
Greatly reduces the severity in the rest
Attenuated virus
Can still establish latency and reactivate
Question: How long will immunity last?

53. Complications of Zoster
Postherpetic Neuraligia
Affects % of zoster patients over 50
Pain may persist for months or even years

54. Alpha Herpesviruses Site of Latency
Herpes Simplex Virus type 1 Sensory neurons
Herpes Simplex Virus type 2 Sensory neurons
Varicella Zoster Virus Sensory neurons
Beta Herpesviruses
Cytomegalovirus Lymphocytes
Human Herpesvirus 6 CD4 T cells
Human Herpesvirus 7 CD4 T cells
Gamma Herpesviruses
Epstein-Barr Virus B lymphocytes
Human Herpesvirus 8 Sarcoma tissue

55. Transmission of CMV In utero Early childhood (saliva, etc.)
Venereal in young adults
Blood transfusion
Organ transplantation

56. Clinical Manifestations of CMV
Normal Host:
Asymptomatic in the majority of cases
Infectious mononucleosis
Congenital CMV:
Primary CMV infection in 3rd trimester of pregnancy of a seronegative mother
Immunocompromised:
Pneumonitis in bone marrow transplants
Retinitis in AIDS patients

60. Alpha Herpesviruses Site of Latency
Herpes Simplex Virus type 1 Sensory neurons
Herpes Simplex Virus type 2 Sensory neurons
Varicella Zoster Virus Sensory neurons
Beta Herpesviruses
Cytomegalovirus Lymphocytes
Human Herpesvirus 6 CD4 T cells
Human Herpesvirus 7 CD4 T cells
Gamma Herpesviruses
Epstein-Barr Virus B lymphocytes
Human Herpesvirus 8 Sarcoma tissue

61. EBV Mono

62. EBV mononucleosis

65. Heterophile Antibody (IM)
EBV induces many cellular proteins
An antibody against one of these new celular proteins is able to agglutinate sheep red blood cells
EBV monucleosis is heterophile antibody positive
CMV mono is heterophile antibody negative

66. IM Serology VCA IgM rises and falls early in infection
VCA IgG antibodies persist
EBV mononucleosis is heterophile antibody positive
CMV mononucleosis is heterophile antibody negative; no antibodies to VCA of EBV

67. Antiviral therapy

68. Acyclovir
Ganciclovir
Deoxyguanosine
Deoxyadenosine
Ribavirin
Vidarabine