The document provides a comprehensive overview of human herpes viruses (HHVs), highlighting their characteristics, transmission, clinical manifestations, and laboratory diagnosis. It discusses the different types of herpes viruses affecting humans, including HSV-1, HSV-2, VZV, CMV, EBV, HHV-6, HHV-7, and HHV-8, detailing their associated diseases and paths of infection. Treatments, preventive measures, and specific clinical findings related to each type of herpes virus are also examined.

1. Human Herpes Virus
(HHVs)

2. Introduction
• It’s akind of envelopedDNAvirus.
• Icosahedralcore surrounded by a
lipoprotein envelope.
• linear double-stranded DNA.
• Large (120–200 nm in diameter), second
in size only to poxviruses.
• Capsid surrounds DNA core and
over the capsid is tegument (a
protein-filled region).
• Nuclear membrane derived lipid bilayer
containing viral glycoproteins

3. HSV-1
HSV-2
VZV
EBV
CMV
HHV-6
HHV-7
HHV-8
The Herpes virus family
includes 8 different enveloped
DNA-containing viruses that
only affect human beings.

4. Subfamily Duration of replication
and Cytopathology
Site of latency Species
Official name Common name
Alpha Short, Cytolytic Neurons HHV 1 Herpes simplex virus 1
HHV 2 Herpes simplex virus 2
HHV 3 Vericella-zoster virus
Beta Long, Cytomegalic Glands, kidney HHV 5 Cytomegalovirus
Long,
lymphoproliferative
Lymphoid tissues
(T cells)
HHV 6
HHV 7
Human herpes virus 6
Human herpes virus 7
Gamma Variable,
lymphoproliferative
Lymphoid tissues
(B cells)
HHV 4 Epstein-Barr virus
HHV 8 Kaposi’s sarcoma
associated herpes virus

5. • Herpes simplex virus Type1(HSV-1)and Type2(HSV-2)
are distinguished by two main criteria
– Antigenicity
– location of lesions.
• HSV-1: abovethe waist,primarily in adults
• Acute gingivostomatitis,
• Recurrent herpes labialis (cold sores),
• Keratoconjunctivitis (keratitis),
• Encephalitis
• HSV-2: belowthewaist
• herpes genitalis(genital herpes),
• Neonatal encephalitis and other forms of neonatal herpes
• Aseptic meningitis
• Humans are the natural hosts of both.
Herpessimplexvirus

7. • DNA released in the cytoplasm
• DNAmigrates to the nucleus
• mRNA(transcription) synthesis takes place in the nucleus by using host RNA
polymerase
• mRNAtransported to thecytoplasm
• Newviral proteins made and migrate to nucleus
• Genomic DNA (replication) synthesis takes place in the nucleus by using
viral DNA polymerase
Hsv replication

8. • HSV 1: transmitted primarily in saliva.
• HSV2:transmitted by sexualcontact
• Oral–genitalsexualactivity: HSV-1 infections of the
genitals and HSV-2 lesions in the oral cavity.
– 10–20% of cases
Hsv transmission

9. • causes several forms of primary and recurrent disease.
• Gingivostomatitis
– Occurs primarily in children and is characterized by fever, irritability,
and vesicular lesions in the mouth.
– The primary disease is more severe and lasts longer than recurrences.
– The lesions heal spontaneously in 2 to 3 weeks.
– Many children have asymptomatic primary infections
• Herpeslabialis
– fever blisters or cold sores is the milder, recurrent form
– characterized by vesicles, usually at the mucocutaneous junction of
the lips or nose
– Recurrences frequently reappear at the same site.
Clinical findingsof HSV1

10. • Keratoconjunctivitis
– characterized by corneal
ulcers and lesions of the
conjunctival epithelium.
– Recurrences can lead to
scarring and blindness
• Encephalitis
– necrotic lesion in one
temporal lobe.
– Fever, headache, vomiting,
seizures, and altered mental
status
Clinical findingsof HSV1

11. • Herpeticwhitlow
– pustular lesion of the skin of the finger or hand.
– It can occur in medical personnel as a result of
contact with patient’slesions.
• Herpesgladiatorum
– wrestlers and others who have close body
contact.
– vesicular lesions on the head, neck, and trunk.
• Disseminatedinfections,
– such as esophagitis and pneumonia,
– occur in immunocompromised patients with
depressed T-cell function.
Clinical findingsof HSV1

12. • Genitalherpes
– painful vesicular lesions of the male and
female genitals and anal area
– The lesions are more severe and protracted
in primary disease than in recurrences.
– Primary infections are associated with fever
and inguinal adenopathy.
Clinical findingsof HSV2

13. • Neonatalherpes
– originates chiefly from contact with vesicular
lesions within the birth canal.
– varies from severe disease (e.g., disseminated
lesions or encephalitis) to milder local lesions
(skin, eye, mouth) to asymptomatic infection.
– prevented by performing cesarean section on
women with either active lesions or positive viral
cultures.
Clinical findingsof HSV2

14. • Both HSV-1 and HSV-2 infections are associated with E.M.
• central red area surrounded by a ring of normal skin outside of
which is a red ring
• “target” or “bull’s eye”lesion.
• lesions are typically macular or papular
• occur symmetrically on the trunk, hands, and feet
• Many drugs, especially sulfonamidesamong the
antimicrobial drugs, commonly cause erythema
multiforme.
• Other associated MCO: Mycoplasma pneumoniae and viruses
such as hepatitis B virus and hepatitis C virus.
• Erythema multiforme major, also known as
StevensJohnson syndrome
– Fever, erosive oral lesions,
– Extensive desquamating skin lesions.
Erythemamultiforme

15. A. Specimens:- Vesicle fluid, skin swab, saliva, corneal scrapings,
brain biopsy and CSF
B. Microscopy:-
 Toluidine blue stained smear-
Multinucleated giant cells with
faceted nuclei and homogeneously stained
‘ground glass’ chromatin(Tzanck cells).
Giemsa stained smear-
Cowdry type A intranuclear
inclusion bodies.
Laboratorydiagnosis
A Tzanck smear : multinucleated
giant cells

16. Electron microscopy- Virus particles demonstrated
Immunofluorescent staining- Virus antigen demonstrated
C. Tissue culture and Isolation:-
 Cell lines- Human fibroblasts, Hep-2 cells, vero cells and
chorioallantoic membrane.
 Typical cytopathic changes (swollen, rounded cells) appear
in 1-5 days.

17. D. Serology:-
 Useful in the diagnosis of primary infection.
 Detection of virus specific IgM antibody or rising titre of
antibody by ELISA, CFT, RIA, neutralisation and
immunofluorescence.
E. Polymerase Chain Reaction (PCR):- DNA detection

18. • Acyclovir:treatment of choice
– shortensthe durationof the lesions
– reducesthe extentofsheddingof the virus
• Penciclovir(a derivative of acyclovir)
• Valacyclovirandfamciclovir:Genital herpes and in the
suppression of recurrences.
treatment

19. • avoiding contact with the vesicular
lesion or ulcer.
• Cesarean section is recommended for
women who are at term and who have
genital lesions or positive viral cultures.
prevention

20. • Clinical chicken pox (primary infection)
• 90%of cases before age 10, peak incidence 2- 8 years
• Virusentry through inhalation
• Replicates in respiratory tract and invades lymph
nodes.
• Viremia: spreads virus to target organs
• Incubation period 14-18 days
Vericellazoastervirus

21. VaricellaZoster
•Varicella(chicken Pox) and Herpes zoster are different
manifestation of the same virus infection.
•Chicken pox follows infection in non immune patients,
while herpes zoster occur in those patient who had
chicken pox but now have low immunity –reactivation
of latent virus (chicken pox caught but zoster
reactivated)

22. • Rash appears first on head, neck, trunk
• Vesicles contain clear fluid (itch)
• Newvesicles appear during first week
• Mildfever, malaise, headache
• Recovery in 2 weeks
• Adultinfections more severe (pneumonia)
• Neonatal infection(encephalitis)
• Immunosuppressed (severe progressive infection)
Vericellazoastervirus (chickenpox)

23. • Shingles: reactivation of varicella-zoster
• DNAremains latent in ganglia
• Occurrence increases with age (50% over 50 yrs)
• Onsetof pain occurs before appearance of vesicles
• Usually unilateral
• Immunosuppressed patients especially
vulnerable
Vericellazoastervirus(shingles)

24. Vzv (superinfection)

25. Laboratory Diagnosis
Diagnosis is usually clinical.
A. Specimens:- Scrapings or fluid of vesicles
B. Microscopy:-
 Multinucleated giant cells and
type A intranuclear inclusion
bodies are seen in smears stained
with toluidine blue, Giemsa or
Papanicolou stain.
 Electron microscopy- Virus particles demonstrated
 Immunofluorescent staining- Virus antigen demonstrated
C. Culture and Isolation:-
 Cell lines- Human amnion, human fibroblast, HeLa or Vero
cells.

26. Cytopathic Effect of VZV in cell culture: Note the ballooning of cells. (Coutesy of
Linda Stannard, University of Cape Town, S.A.)
Cytopathic Effect of VZV

27. • Prevention
– immunoglobulin for patients at risk
– Vaccine: live vaccine (VARIVAX, Merck & Co.)
– Recommended dose
• For susceptible children aged 12 months to 12
years is one 0.5 ml dose subcutaneously
• For susceptible adolescents aged 13 years and
adults is two 0.5 ml doses 4 to 8 weeks apart

28. CYTOMEGALOVIRUS

29. Largest (150-200 nm) virus in the herpesvirus family.
Also called salivary gland viruses of humans and animals
Leads to prolonged latency in infected host.
Most common cause of congenital defect.
Transmitted through birth canal, saliva, breast milk, blood
products and sexual exchange of body fluids.
An individual infected with virus carries it for life.
CYTOMEGALOVIRUS

30. CONGENITAL CMV INFECTION
•Transmission from mother to child through
placental blood or ascending from cervix.
•Congenital infection can be asymptomatic or
symptomatic
Asymptomatic child normal can develop mental
retardation and neurological defects
Symptomatic disease acquired during pregnancy
Microcephaly, hepatosplenomegaly, jaundice,
mental retardation and hearing loss

31. Perinatal occurs through infected birth canal or breast
milk child develop lymphadenpathy, hepatitis and
pneumonitis
CMV Mononucleosis disease of young adult aquired
from person to person , blood transfusion patient.
ACQIRED CMV INFECTION
•CMV in immunocompromised opportunistic infection pneumonitis, hepatitis,
encephalitis, retinitis and many other symptoms
•CMV in immunocompetent
Produces mononucleosis type symptoms
Infection transmitted by sexual and oral contact

32. CMV - Infections

33. CMV affecting retina

35. Laboratory Diagnosis
A. Specimens:- Urine, saliva, other body fluids
B. Microscopy:-
 Demonstration of cytomegalic cells-
Enlarged cells with large intranuclear
“owl’s eye” appearance inclusions.
C. Culture and Isolation:-
 Grown in human fibroblast culture.
 Cytopathic effects take 2-3 weeks to appear
(due to slow replication).
D. Serology:-
 CMV specific IgM can be detected in the serum by
ELISA.

36. EPSTEIN-BARR VIRUS (EBV)
A ubiquitous herpesvirus.
EBV infection occurs in infancy and childhood in developing countries
and in adolescence in developed countries.
Infection leads to latency, periodic reactivation and lifelong
persistence.
Sources of infection- Saliva of infected persons
Mode of transmission- Intimate oral contact, as in kissing (Kissing
disease).

37. Epstein Barr virus (EBV)-associated diseases
•Infectious Mononucleosis
•Burkitt lymphoma
•Nasopharyngeal carcinoma
•Lymphoproliferative Disease
•Hodgkin’s Disease, EBV-assoc. NHL
•Gastric carcinoma

38. Infectious Mononucleosis
(Glandular Fever)
An acute self-limiting illness usually seen in
non-immune young adults.
IP:- 4-8 weeks
Characterized by fever, sore throat,
lymphadenopahy and the presence of
abnormal lymphocytes in peripheral blood
smears.
A mild transient rash may be present.
In most cases, spontaneous resolution of the
disease occurs in 2-4 weeks.
Leads to mental and physical fatigue in
convalescence.

39. IM – Clinical presentation

40. Laboratory Diagnosis
A. Specimen:- Blood, Saliva, Lymphoid tissue
B. White Blood Cell Count:-
 Leucopenia, in initial phase but later there is leucocytosis.
 Appearance of abnormal or atypical mononuclear cells

41. C. Paul- Bunnel Test
 During infectious mononucleosis, heterophile antibodies
agglutinate sheep erythrocytes.
 Procedure:-
• Inactivated serum (56°c/ 30 min.) in doubling dilutions is
mixed with equal volumes of a 1% suspension of sheep
erythrocytes.
• Incubate at 37°c for 1hour
• Examine for agglutination.
 Result:- An agglutination titre
of 100 or above is suggestive
of infectious mononucleosis.
+ve -ve

42. D. Other serological tests:-
Immunofluorescence or ELISA

43. HUMAN HERPES VIRUS 6 & 7(HHV 6 AND HHV 7)
First isolated in 1986.
They are transmitted mainly through contact with saliva and
through breast feeding.
>90% of the world population by age 2 are HHV-6 and 7
positive.
Like other herpesviruses, HHV-6 and HHV-7 remains latent in
the body after primary infection and reactivates from time to time.
Infects CD4+ T-cells

44. CLINICAL MANIFESTATIONS
Primary HHV-6 infection is associated with
Roseala Infantum, which is a classical disease
of childhood..
 A spiking fever develops over a period of 2 days
followed by a mild rash. The fever is high enough
to cause febrile convulsions.
There are reports that the disease may be
complicated by encephalitis.

45. If primary infection is delayed until adulthood, there is a small
chance that an infectious mononucleosis-like disease may develop in
a similar manner to EBV and CMV.
There is no firm evidence linking HHV-6 to lymphomas or
lymphoproliferative diseases.
There is no firm disease association with HHV-7 at present.

46. HUMAN HERPESVIRUS 8 (HHV 8)
First detected in 1994.
Also called as Kaposi’s sarcoma associated herpes
virus (KSHV)
Transmitted through- Exchange of body fluids, sexual
contact, organ transplantation, saliva (inefficient)
Associated
Kaposi’s Sarcoma
Multicentric Castleman’s Disease (lymphoproliferative disorder of B
cells)
body cavity based Lymphoma.

47. Kaposi’s sarcoma
Classic Kaposi's sarcoma (CKS) is a
neoplasm characterized by purplish,
reddish blue, or dark brown/black
macules, plaques, and nodules on the
skin.
mucous membranes of mouth and
gastrointestinal (GI) tract and regional
lymph nodes may be affected later in
the course.
Biopsy for definitive diagnosis
radiation therapy, excision,
cryotherapy, chemotherapy
emedicine.medscape.com/article/279734-overview

48. A 7 years old boy developed multiple painful vesicle
over the lips and buccal mucosa. His parents revealed
that two children of of his school had similar
presentation few days back. Scraping taken from the
lesions demonstrated the presence of multinucleated
giant cells (Tzanck cells).
a. What is the probable diagnosis?
b. How is the infection diagnosed in the laboratory?

49. • A neonate has hepatosplenomegaly. His urine was
stained with Giemsa stain which revealed owl’s eye
appearance inclusions. Which will be the probable
cause?