This document provides information on herpesviruses and several human herpesvirus types. It discusses how herpesviruses can cause chronic, latent, and recurrent infections. It describes the structure and properties of herpesvirus particles. It also provides details on specific human herpesviruses like herpes simplex virus types 1 and 2, varicella zoster virus, cytomegalovirus, and their associated diseases. Clinical manifestations, transmission, diagnosis, treatment and prevention are covered for some of these viruses.

1. DP Monga-DMIP
Medical Virology for Yr II
4.7 and 4.8 HERPESVIRIDAE

Prof DP MONGA
 DMIP,FOM


2. DP Monga-DMIP
HERPESVIRUSES
'Herpein' - 'to creep' =
chronic/latent/recurrent infections

3. DP Monga-DMIP
HERPES VIRUS TYPES THAT
INFECT HUMANS
 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 (exanthum subitum or
roseola infantum)
 Human herpes virus 8 (Kaposi's sarcoma-
associate herpes virus)

4. DP Monga-DMIP
HERPESVIRUSES
 Capacity to persist in host indefinitely
in nucleus of the cell
Every vertebrate species has at least one host
specific herpesvirus
Varicella zoster and herpes simplex viruses
establish latent infections in neurons ↓
reactivation
 Some are cancer causing

5. DP Monga-DMIP
Herpesvirus Virion
 Spherical 150- 250 nm Icosahedral
 Enveloped ds DNA linear 124-235 kbp
 More than 35 proteins in virion
 Envelope:8nm spikes viral glycoproteins.Fc
receptors.
 Replication nuclear, bud from nuclear membrane
 Infection: Lytic, latent and recurrent

6. DP Monga-DMIP
Herpes virion -Properties
 Size:150-200nm
 Envelope:Present; associated glycoproteins-spikes.
 Tegument:Protein-filled region between capsid and envelope.
 Capsid:Icosahedral, 95-105nm diameter; 162 hexagonal
capsomers.
 Core:Toroidal (DNA around protein), ~75nm diameter.
 Genome: Large, 130-230kbp and encode at least 100 different
proteins and many virus-specific enzymes , Linear, d/s DNA,,
G+C 31-75 %
 Replication:Nuclear.
 Assembly:Nuclear.
 Common Antigens:None!

7. DP Monga-DMIP
Herpesvirus Particle
All herpesviruses - identical
morphology
Cannot be distinguished from
each other under electron
microscopy.

8. DP Monga-DMIP
Classification of Human Herpesviruses
 Family Herpesviridae
Sub family –herpesvirinae
Sub family Genus Official name Common
Alpha simplex HHV 1 Herpes simplex type 1
HHV 2 Herpes simplex type 2
________________________________________
Varicello HHV 3 Varicella Zoster virus
_________________________________________________________
Beta herpevi Cytomegalo HHV 5 Cytomegalovirus
Roseolo HHV 6 HHV 6
HHV 7 HHV 7
____________________________________________________________
Gamma her Lymhocrypto HHV 4 Epstein-Bar virus
Rhadino HHV 8 Kapossi’s sarcoma associated
herpes virus

9. DP Monga-DMIP
Herpes Simplex Viruses
 Distinct HSV-1 and HSV-2
 Differentiated restriction enzyme assay of DNA
 Extremely widespread-humans
 Broad host range-replicate many different types of
cells and infect different animals.Humans only natural
hosts
 Grow rapidly-highly cytolytic
 Spectrum of diseases-gingivostomatitis-
keratoconjunctivitis,encephalitis, genital diseases
 Infections of newborns
 Latent infection-nerve cells
 Histopathology-balooning of infected cells, inclusion
bodies and formation of giant cells

10. DP Monga-DMIP
Latency
 Escape immune response
 Persist lifelong in latent state
Normal humans → mostly trigeminal ganglia
To some extent: cervical, sacral, vagal
ganglia
 Virus persistence → low grade productive
virus infection → no lysis
 True latency →virus non replicative

11. DP Monga-DMIP
Reactivation
 Stress Physical/ psychological
 Pneumococcal infection
 Meningococcal infection
 Fever
 Irradiation
 Menstruations
 Immunosuppression
 Cytotoxic drugs
 HIV
 Organ graft etc

12. DP Monga-DMIP
Transmission of HSV
 Herpes simplex
virus infections are very
contagious and are spread by
direct contact with the skin
lesions.
 Saliva HSV 1
 Respiratory route HSV 1
 Sexual contact HSV 2

13. DP Monga-DMIP
Clinical manifestations
 Oropharyngeal disease-HSV-1
 Keratoconjunctivitis-HSV-1
 Genital herpes-HSV-2, though HSV-1too
 Skin infections-HSV-1 and HSV-2
 Encephalitis-sporadic fatal-HSV-1
 Neonatal Herpes-from mother- HSV-2, from other contacts
HSV-1 & HSV2
 Immunocmpromised hosts
 people who have HSV infections may be
contagious even when they do not have any
skin lesions, which is called asymptomatic
shedding

14. DP Monga-DMIP
Genital Herpes
 Usually HSV- 2
 Primary infection severe-3 weeks
 Vesiculcerative lesions of penis-male
 Cevix, vulva,vagina,perineum-females
 Very painful
 Fever, malaise, dysuria,
 Lymphadenopathy
 Recurrence common-mild
 sexual partners, mother-infant pairs, or persons
involved in a commonsource of outbreak

15. DP Monga-DMIP
HSV Clinical manifestations
Cold sore of recurrent herpes labialis

16. DP Monga-DMIP
HSV 1 COLD SORE

17. DP Monga-DMIP
HSV-1 COLD SORE

18. DP Monga-DMIP
HSV 1-Lesions around eye

19. DP Monga-DMIP
HSV Clinical manifestations
 HSV Keratitis- Dendritic ulcers

20. DP Monga-DMIP

A Primary herpes gingvostomatitis
 B HSV latent infection-trigeminal ganglia

21. DP Monga-DMIP
 Herpes whitlow (Herpes skin infection)

22. DP Monga-DMIP
HSV 1-Lesions on Finger

23. DP Monga-DMIP
HSV-2

24. DP Monga-DMIP
Genital Herpes simplex
Typical Lesion on Penis

25. DP Monga-DMIP
Genital Herpes simplex
Typical Lesion on Penis

26. DP Monga-DMIP
HSV-Penis- Healing

27. DP Monga-DMIP
Genital Herpes simplex
Typical Lesion on Penis

28. DP Monga-DMIP
Genital Herpes-Female

29. DP Monga-DMIP
Immunity
 New born-passive 6 months
 6 mo-2 y-highly susceptible
 Transplacental antibodies↓ infection
 Primary infection →antibodies +virus↓
latency
Recurrent → antibodies change/modify
subsequent disease
 Both antibody-mediated and cell-mediated
reactions are clinically important.

30. DP Monga-DMIP
Diagnosis
 Light microscopy-intranuclear inclusions
infected cell →ballooning & fusion
 Electron microscopy ?
 Antigen detection
 Virus culture-HSV 1, HSV 2 easiest to culture typical
CPE
 Serology –Antibodies-4-7 d after infection CFT/
IHA/ELISA/RIA
 Restriction endonuclease analysis of viral DNA or
DNA sequencing can be used to distinguish
between the two types and among strains of each
subtype.

31. DP Monga-DMIP
Is there any treatment for
herpes?
 There is no treatment that can cure
herpes, but antiviral medications can
shorten and prevent outbreaks during
the period of time the person takes the
medication. In addition, daily
suppressive therapy for symptomatic
herpes can reduce transmission to
partners

32. DP Monga-DMIP
Antiviral chemotherapy
Inhibit DNA synthesis-inhibit viral
replication
 Acyclovir-drug of choice
 Famiclovir
 Valaciclovir better absorption
 Idoxyuridine
 Vidarbine

33. DP Monga-DMIP
HSV Vaccines
 Primary infection not worth preventing
Only experimental
 vaccines- purified glycoprotein ag
-Recombinant HSV 2 subunit vaccines
-Synthetic peptides

34. DP Monga-DMIP
THANK YOU
NEXT LECTURE OTHER
HERPES VIRUSES

35. DP Monga-DMIP
HUMAN HERPES VIRUS
TYPE-3
 VARICELLA- ZOSTER VIRUS
Two almost universal human diseases
1 Chickenpox (Varicella)-
exanthema of childhood
2Herpes zoster (Shingles)
Disabling disease of aged persons or
immunocompromised patients

36. DP Monga-DMIP
Varicella-Zoster
 Varicella-Chicken pox ↓
Latency ↓
Zoster-Shingles
 VZ virus causes two distinct clinical
entities
 Both diseases same virus
 Morphologically identical HSV
 Only one serotype-x HSV
 No animal reservoir (except primates)
 Grow readily cell sulture
 Intranuclear inclusions, balooning, swelling

37. DP Monga-DMIP
Varicella-Zoster Virus
Normal individuals
 Primary infection (chickenpox) is one of the classical rash
diseases of childhood.
 Following primary infection, the virus remains latent in the
cranial-spinal ganglia.
 Reactivation leading to the appearance of shingles occurs
in 10-20% of infected individuals and usually occurs after
the fourth decade of life. Usually, only one episode of
reactivation occurs.

38. DP Monga-DMIP
Chicken pox. Each lesion has its
own red base

39. DP Monga-DMIP
Chicken pox-lesions in various
stages

40. DP Monga-DMIP
Immunocompromised individuals
Primary infection
 severe in children -anti malignancy drugs- leukaemia
and lymphoma.
 Life-threatening complications such as disseminated
varicella, pneumonia, and encephalitis are much more
likely to be seen.
Reactivation
 Immunocompromised →herpes zoster, appear at an
earlier age and more than one episode may occur.
 Severe, disseminated disease may occur but fatality
is rare.

41. DP Monga-DMIP
Small blisters form during the initial stage of
shingles (left)
followed by a full skin rash resembling
chickenpox lesions (right).

42. DP Monga-DMIP
Varicella Zoster Virus
 Herpes zoster -Shingles

43. DP Monga-DMIP
Properties of VZ virus
 a ubiquitous and extremely contagious
infection
 Morphologically identical HSV
 No animal reservoir
 Intranuclear inclusions
 CPE more focal much more slow
 Same virus chicken pox and zoster
 Only one serotype X HSV

44. DP Monga-DMIP
Varicella Highly contagious Very
common disease of children
 Route URT / conjunctiva ↓
Circulates in blood ↓
multiple cycles of replication ↓
localizes in skin → viral infection of capillary
endothelial cells
Neonatal / complicated →Other organs
Lungs most severe
high mortality

45. DP Monga-DMIP
Vaeiclla or Chicken pox
 Always acute disease
 IP 7-23 d-infectious 2 d before rash
 Rash-face, neck trunk, axillae, limbs,
shoulder blades
 Maculae-papule-vesicle-crust- in crops
 Duration of disease-7 and 10 days, up to 2-4
wks
 Complications rare
 Mortality very low

46. DP Monga-DMIP
Chicken pox-neonatal
 Varicella from mother
 Virus –different internal organs
 High mortality about 30 %
Congenital Varicella
 Varicella in pregnancy rarely crosses
placenta
“Congenital varicella syndrome”

47. DP Monga-DMIP
Chicken pox-adults (Primary)
 Serious
 Pneumonia most common complication
 Mortality 10-40 %

48. DP Monga-DMIP
ZOSTER or Shingles
 Herpes zoster, a sporadic disease, is the
consequence of reactivation of latent VZV from the
dorsal root ganglia.
 No history of recent exposure
 Herpes zoster occurs at all ages, but its incidence is
highest among individuals in the sixth decade of life
and beyond. Recurrent herpes zoster is exceedingly
rare except
in immunocompromised hosts AIDS (hemorrhagic
vesicles and pustules)
 Unilateral vesicular eruption , often associated with
severe pain.

49. DP Monga-DMIP
Zoster in AIDS patient

50. DP Monga-DMIP
Zoster
 Skin lesions similar to varicella
 Often only single ganglion involved
 Limited to skin of an individual dorsal
root ganglion
 Acute inflammation of sensory nerves
and ganglia
 Trigger of reactivation ?? Waning
immunity

51. DP Monga-DMIP
Clinical manifestations- Zoster
 Very painful
 Virus →nerve to cell
 Area supplied by nerve-crop of vesicles
 Incapacitating disease
 Unilateral common- trunk, head, neck
 Any age
 Facial paralysis (trigeminal nerve)

52. DP Monga-DMIP
Diagnosis
 Cytology-multinucleated giant cells
 Intracellular viral antigen-IF
 EM diff poxviruses
 Molecular methods-PCR,EIA
 Clinical
 Serology-CF, Nt (cell culture)

53. DP Monga-DMIP
Immunity
 Primary Varicella-life long immunity to
Varicella
 Zoster can occur
 CMI important in recovery

54. DP Monga-DMIP
Treatment and Prevention
 Acyclovir -severe varicella or zoster infections.
 A live attenuated vaccine controversial in
immunocompromised individuals
.
 VZIG can be used to prevent primary infection in
susceptible individuals.

55. DP Monga-DMIP
Cytomegalovirus
Human herpes Virus Type-5

56. DP Monga-DMIP
Cytomegalovirus Herpes virus
type-5 (CMV)
 Spherical-Icosahedral 200 nm,the largest of
the Herpesviruses, genome ~240kbp
 CMV infection are 'slow' - 7-14 days c.f. 24-
48h for HSV
 CMV infection is common more than 50 %
population experienced infection by the age
of 40
 Most infections are asymptomatic, symptoms
in people with immune defects (T-cell defects)
/pregnancy / newborns (congenital)

57. DP Monga-DMIP
Cytomegalovirus
Normal individuals
 Primary infection is usually asymptomatic,
occasionally an infectious mononucleosis-like
illness may be seen.
 Reactivations or re-infections are common
throughout life and are usually asymptomatic.

58. DP Monga-DMIP
Immunocompromised individuals
 Both primary and recurrent infection may
lead to symptomatic disease.
 Primary CMV infection is usually more
severe than recurrent infection, with the
exception of bone marrow transplant
recipients, where primary and recurrent
infections are just as severe.

59. DP Monga-DMIP
Clinical Manifestations
 Fever
 Pneumonitis
 Hepatitis
 Gastrointestinal manifestations eg. colitis
 Encephalopathy
 Retinitis
 Poor graft function
Pneumonitis is the most severe manifestation,
mortality rate of 85% in the absence of
treatment.

60. DP Monga-DMIP
AIDS Patients
 CMV disease is present in 7.4% to 30%
of all AIDS patient.
 Sight-threatening retinitis, colitis, and
encephalopathy are the most common
manifestations of CMV disease in AIDS
patients. Pneumonitis is extremely rare.

61. DP Monga-DMIP
Solid organ transplant recipients
e.g. renal, liver, heart
 Most common infection, leading cause of
morbidity and mortality.
 Occurs 1 - 3 months following transplant.
 Primary infection more severe than
recurrent infection.
 Fever, pneumonitis, GI manifestations,
hepatitis, and poor graft function.

62. DP Monga-DMIP
Congenital CMV Infection
 Mother infected in pregnancy → fetus at
high risk
 Maternal infection usually asymptomatic
 Fetal infection asymptomatic to severe
and disseminated
 Fetus damaged at any stage
 Severe developmental defects
 Mental retardation / deafness

63. DP Monga-DMIP
Perinatal CMV Infection
 Infected birth canal / maternal milk or
other secretions
 Protracted interstitial pneumonitis
 Poor weight gain, adenopathy, rash.
Hepatitis and anemia persist for months
to years

64. DP Monga-DMIP
Laboratory Diagnosis (1)
 1 Cytology / histology –large cytomegalic
25-35 um intranuclear inclusions-”owl’s
eye”
 Culture -Gold standard
 Nucleic acid antigen detection IFA, IE
 Serology
 PCR

65. DP Monga-DMIP
Management (1)
 Ganciclovir
 Forscarnet -.
 Cifofovir (HPMCC) -
 Fomivirsen -.
 CMV hyperimmune globulin - found to
be effective against CMV pneumonitis.

66. DP Monga-DMIP
Prevention
 Vaccination - an experimental live
attenuated vaccine known as the
Towne strain is available-problems
 Subunit vaccines are being developed.

67. DP Monga-DMIP
Human Herpes Virus Type-
4
Epstein-Barr Virus
One Target cells B cells-
Immortalization of cells

68. DP Monga-DMIP
Epstein-Barr Virus
 Ubiquitous
 Acute infectious mononucleosis /
nasopharyngeal carcinoma
 Burkitt’s Lymphoma and other
lymphoproliferative disorders
 Dual cell tropism for human B-lymphocytes
(generally non-productive infection) and
epithelial cells (productive infection).
 Highly host specific-No suitable animal host

69. DP Monga-DMIP
Epstein-Barr Virus-clinical---
 Primary infection-infected saliva-IP 30-50 days-
initiate inf in oropharynx →replication B cells or
epithelial cells
 Most PI asymptomatic/ subclinical in child
 Sore throat, head ache
 Fever, malaise, fatigue
 Enlarged LN
 Few-hepatitis

70. DP Monga-DMIP
Epstein-Barr Virus-clinical---
Young adults-
 Infectious mononucleosis-autoantibodies
Self limiting lasts 2-4 weeks
Symptoms like primary infection
 Oral Hairy Leukoplakia: Wart like growth on
tongue of some HIV persons and transplant
patients.It is an epithelial focus of EBV
replication
 Tumors-Burkitt’s lymphoma,naso pharyngeal
carcinoma

71. DP Monga-DMIP
Hairy leukoplakia often presents as white
plaques or warts on the lateral surface of the
tongue and is associated with EBV infection.

72. DP Monga-DMIP

73. DP Monga-DMIP
Burkitt's lymphoma
 Tumor of jaw
 African children/ young adults
Contain EBV DNA
Most cases express EBNA 1 antigen

74. DP Monga-DMIP
Burkitt’s lymphoma

75. DP Monga-DMIP
Burkett's lymphoma

76. DP Monga-DMIP
Nasophtyngeal carcinoma
 Common in males of Chinese origin
 Genetic and environmental factors
EBV DNA
High levels of antibody to HBV

77. DP Monga-DMIP
Human Herpes Virus 6
 HHV 1986
 latent following primary infection.
 HHV-6 HHV-6-Early life-Roseola infantum
“sixth disease” → persists for life –
reactivation in pregnancy-encephalitis?
neurological manifestations

78. DP Monga-DMIP
Human Herpes Virus-7
 HHV7-199
 Circulating T cells
 Immunologically distinct from HHV-6
 Ubiquitous
 Infections in childhood (later than HHV-6)
 Persistent infection in salivary glands

79. DP Monga-DMIP
Human Herpes Virus 8
 1990
 lymphotropic
 associated with Kaposi’s sarcoma (KSHV)
 Some other lymphomas.
HHV-8 does not have a ubiquitous distribution
 Sexually transmitted among homosexual men
 Common in africa-early life-nonsexualroutes-saliva
 Fosarnet, Ganiclovir, Cidofovir.

80. DP Monga-DMIP
Herpes B Virus
 Monkeys
 Highly pathogenic humans
 Transmissibility limited-association with
monkeys
 High mortality about 70 %
 Acute ascending myelitis and
encephalomyelitis

81. DP Monga-DMIP
THANK YOU