4. HERPES VIRUSES in a range of prominent medical or veterinary diseases

herpesviruses in a range of prominent medical or veterinary diseases makes them one of the most important virus families

1. HERPES VIRUSES
HERPES VIRUSES

2. •The involvement of herpesviruses in a range of
prominent medical or veterinary diseases makes them
one of the most important virus families.
•Family Herpesviridae comprises over 100 viruses
that infect a wide range of vertebrates, including
fish, amphibians, reptiles, birds and mammals including
humans.
Introduction Introduction

3. •All herpesviruses have large enveloped virions containing
double-stranded linear DNA genomes which exhibit
considerable diversity of size and structure.
•Herpesviruses vary greatly in their pathology and biology, but
one common feature is their ability, following primary
infection, to establish lifelong latent infections which can
recrudesce to cause a second round, or even recurrence of
disease.

4. St
ructure of Herpes viruses
St
ructure of Herpes viruses
•Capid is icosahedral(162 capsomers)
•Enclosing core contains ds DNA
•Nucleocapisd surrounded by lipid envelope
•Envelop carries surface spikes (8mm)
•Between envelope and capsid is an amorphous structure called
tegument.

5. H
erpes simplex virus.
H
erpes simplex virus.
N
egative stain
N
egative stain

6. REPLICATION
•Herpesvirus replicate in the host cell nucleus
•They form Cowdry type A intranuclear inclusion bodies.
RESISTANCE
•Susceptible to fat solvents like alcohol, ether, chloroform
and bile salts.

7. •Based on biological, physical and genetic properties
herpesviruses have been divided into 3 subfamilies:
- Alpha-, Beta- and Gamma herpesvirinae.
•To date, 8 different herpesviruses have been identified
whose natural host is humans.

8. Alphaherpesvirinae
•Have a variable host range in cell culture,
•Have a short growth cycle,
•Spread rapidly with efficient destruction of infected cells
•They have the capacity to establish latent infections
primarily in sensory ganglia.
•Example – herpes simplex virus and vericella zoster
virus.

9. Betaherpesvirinae
•By a narrow host range
•Long reproductive cycle in cell culture with slow virus spread.
•Infected cells frequently become enlarged.
•Viruses may become latent in secretory glands and
lymphoreticular cells.
•Example – Cytomegalovirus.

10. Gammaherpesvirinae
•Have a narrow host range
•Replicate in lymphoblastoid cells
•Frequently cause latent infection in lymphoid tissue
•Example – Epstein-Barr virus.

12. Human
herpes type
Name Sub Family
Target cell
type
LatencyTransmission
1
Herpes
simplex-1
(HSV-1)
Alphaherpesvir
inae
MucoepitheliaNeuron Close contact
2
Herpes
simplex-2
(HSV-2)
Alphaherpesvir
inae
MucoepitheliaNeuron
Close contact
usually sexual
3
Varicella
Zoster virus
(VSV)
Alphaherpesvir
inae
MucoepitheliaNeuron
Contact or
respiratory
route
4
Epstein-Barr
Virus (EBV)
Gammaherpes
virinae
B lymphocyte,
epithelia
B lymphocytesSaliva
5
Cytomegalovir
us (CMV)
Betaherpesviri
nae
Epithelia,
monocytes,
lymphocytes
Monocytes,
lymphocytes
and possibly
others
Contact, blood
transfusions,
transplantation,
congenital

13. Human
herpes type
Name Sub Family
Target cell
type
Latency
Transmissio
n
6
Herpes
lymphotropic
virus
Betaherpesviri
nae
T lymphocytes
and others
T lymphocytes
and others
Contact,
respiratory
route
7
Human herpes
virus-7 (HHV-
7)
Betaherpesviri
nae
T lymphocytes
and others
T lymphocytes
and others
Unknown
8
Human herpes
virus-8 (HHV-
8)
Kaposi's
sarcoma-
associated
herpes virus
(KSHV)
Gammaherpes
virinae
Endothelial
cells
Unknown
Exchange of
body fluids?

14. ALPHAHERPESVIRUSESALPHAHERPESVIRUSES ––
HERPES SIMPLEX VIRUS HERPES SIMPLEX VIRUS
•HSV occurs naturally only in humans
•Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2)
HSV type 1 –
•Usually isolated from lesions in and around the mouth
•Transmitted by direct contact or droplet spread from cases or
carriers.
HSV type – 2
•Is responsible for the majority of genital herpes infections
•Commonly transmitted venereally

15. •HSV-1 and HSV-2 are closely related: they cross-react
antigenically, exhibit extensive nucleotide sequence
homology and their genes are functionally homologous.

16. •Differentiating feature :
Antigenic differences can be made out by using type specific
monoclonal antibodies.
On CAM type 2 strains form larger pocks.
Type 2 strains replicate well in chick embryo fibroblast
cells, while type 1 do so poorly.
The infectivity of type 2 is more temperature sensitive.
Type 2 strains are more neurovirulent.
Type 2 strains are more resistant to antiviral drugs

17. P
ATHOGENESIS
P
ATHOGENESIS
•Primary infection is usually acquired in early children
between 2 to 5 yrs of ages.
•Humans are the only natural hosts
•Sources of infection are saliva, skin lesions or respiratory
secretions.
•Route of infection : transmission occurs by close contact
and may be venereal in genital herpes.

18. P
ATHOGENESIS
P
ATHOGENESIS
•The portal of entry in primary infection is the damaged
skin or mucosa and the classic lesion is a vesicle beneath
the keratinized squamous epithelial cells
•Virus spreads to draining lymph nodes producing
lymphadentits.
•Vesicle and surrounding tissue contain a dense infiltrate of
inflammatory cells, mostly mononuclear.
•Lesions usually heal with residual scarring.

19. Herpes simplex virus can set up a primary infection in the Herpes simplex virus can set up a primary infection in the
lips, move to the trigeminal  ganglion where it can remain lips, move to the trigeminal  ganglion where it can remain
latent. Virus can subsequently reactivate, move to the latent. Virus can subsequently reactivate, move to the
original site of infection and result in cold sores original site of infection and result in cold sores

20. H
erpes simplex 1: Cold
H
erpes simplex 1: Cold
s
ores
s
ores

21. •The herpesvirus DNA gets integrated into host cell
genome
•These get reactivated when provoked by various stimuli
such as common cold, fever, pneumonia, stress, exposure
to sunlight.

22. S
ite at which HSV-1 and HSV-2
S
ite at which HSV-1 and HSV-2
ca
use disease in humans
ca
use disease in humans

23. C
LINICAL FEATURES
C
LINICAL FEATURES
1.Cutaneous infection:
•Face (cheek, chin, around mouth & forehead). Common site.
•Typical lesion: fever blister or herpes febrilis, caused by viral
reactivation due to stimuli.
•Occupational: herpetic whitlow seen in doctors, dentists and nurses
•Eczema herpeticum ( generalised eruption in children)
2.Mucosal:
•Buccal mucosa commonly effected.
•Gingivostomatitis (Primary)
•Herpes labialis (Reccurence)

24. H
erpes simplex lesion of
H
erpes simplex lesion of
low
er lip, second day after
low
er lip, second day after
o
nset.
o
nset.

25. H
erpetic gingivitis
H
erpetic gingivitis

26. H
erpetic whitlow on the
H
erpetic whitlow on the
w
rist 
w
rist 

27. 3.Ophthalmic:
•Commonest cause of corneal blindness
•Keratoconjunctivitis
•Follicular conjunctivitis
•Chorioretinitis, a rare condition
4.Nervous system:
•HSV encephalitis: fever & acute focal neurological deficit
•Transverse myelitis or GB syndrome

28. 5.Visceral:
•HSV esophagitis cause dysphagia,substernal pain and wt loss.
•Tracheobronchitis & pneumonitis
•Hepatitis: Uncommon
•Disseminated infection seen in immunocompromised.
6.Genital:
•HG is caused by a virus, herpes simplex virus (HSV) type 2, in
more than 85 percent of cases; type 1 HSV generally causes
herpes labialis but can occasionally cause genital infection.

29. G
enital herpes on the
G
enital herpes on the
p
enis
p
enis
 

 

30. C
lassical primary genital herpes
C
lassical primary genital herpes
aff
ecting the vulva
aff
ecting the vulva

31. Specimens
According to the site of involvement.
Include vesicle fluid, skin swab, saliva, corneal scraping, brain
biopsy and CSF
The diagnosis of genital herpes infection is based on the clinical
features and is confirmed by
L
ab diagnosis
L
ab diagnosis

32. (i)Tzanck smear :
•This is a valuable rapid procedure for the diagnosis of HSV
infection.
•A smear made from the base of lesions is stained with Wright’s or
Giemsa stain.
•The presence of multinucleated giant cells with faceted nuclei and
homogeneously stained ground glass chromatin(Tzanck cells) is
suggestive of HSV infection.
•Cowdary type A intranuclear inclusion bodies may be seen in
Giemsa stained smears.
L
ab diagnosis
L
ab diagnosis

33. Herpes simplex 1 – Histological stain. Herpes simplex 1 – Histological stain.
Note the multinucleate cell with dark Note the multinucleate cell with dark
staining inclusions. staining inclusions.

34. Tissue culture
•Virus can be isolated on human fibroblasts, verocells,
chorioallantonic membrane.
•Swollen rounded cells may appear within 1-5 days
•Some virus stains may give syncytium (fusion of infected
cells) formation
•Diagnosis can be confirmed by immunofluorescent
staining of infected cell culture.

35. Herpes simplex 1 – Human Plaque Assay. Herpes simplex 1 – Human Plaque Assay.
Cells grown on African green monkey cells Cells grown on African green monkey cells
(Phase contrast image)(Phase contrast image)

36. L
ab diagnosis
L
ab diagnosis
(iii) Monoclonal antibodies : The technique, using
specific antibodies directed against HSV-1 and HSV-2, is
still being evaluated (Fluorescent antibody test on brain
biopsy specimens).
(iv) Nucleic acid hybridisation : DNA hybridisation
assays to detect viral nucleic acid is also being evaluated.
(v) Serology: ELISA, CFT, Neutralization test.

37. TREATMENT TREATMENT
•Infection can be treated with acyclovir
•It acts by interfering with viral DNA synthesis by
inhibiting DNA dependent DNA polymearse.
•Used as a ointment in ocular lesions.
•Valaciclovir and famaciclovir are more effective oral
agent for type 2.
•When resistance to these drugs - Foscarnet

38. Va
ricella-Zoster
Va
ricella-Zoster
•Caused by VZV – Varicella (chicken pox) and herpes
zoster(shingles) are caused by a single virus
•Varicella (Chicken pox) follows primary infection in a non-
immune individual; Herpes Zoster is a reactivation of the
latent virus when the immunity is suppressed
•Contact with varicella or zoster can give rise to varicella
•Grows only in cultures of human fibroblasts, human amnion
or HeLa cells
•CPE is similar to that of HSV

39. A
bout Chicken Pox
A
bout Chicken Pox
•Chickenpox is caused by the
varicella-zoster virus
(VZV), also known as
human herpes virus 3
(HHV-3), one of the eight
herpes viruses known to
affect humans.

40. H
istory
H
istory
•Giovanni Filipo an Italian scientist first described the
symptoms of Chicken Pox
•An English physician described a mild case of Small Pox
as “Chicken Pox” in the 1600s
•William Heberden was the fist physician to demonstrate
that Chicken Pox was different than Small Pox

41. Characterized by:
•Fever, Raw, open, itchy sores
•It is very contagious and usually occurs during childhood
(normally 5-9 yrs) , but you can get it at any time in your
life.
•It is most common at the end of winter and the beginning
of Spring

42. •Infects about 70% of all children by 18.
•The rash and fever last for about five days.
•Approximately 4,000,000 people get the chicken pox each year.
•Most children handle the chicken pox well and recover without
any problem within a week.
•Infants less than 6 months old are usually protected from it as
long as their mother carries the antibody to this virus.
•It is unusual to have chicken pox more than once.

43. T
ransmission
T
ransmission
•Persons to person
contact or
sneezing/coughing
•Kids around 6 or 7 will
usually spread it
between each other.

44. Sym
ptoms
Sym
ptoms
•Which then form blisters and spreads to the rest of the body.
Infectivity is more in the early phase of the disease; portal of
entry- respiratory tract or conjunctiva; I.P of 7-23 days.
•Chicken pox often begins with a small fever, body aches and
loss of appetite.
•Within 1 or 2 days, the rash appears, normally starting on the
chest or back.
•At first the rash begins as red spots

45. C
hickenpox rash
C
hickenpox rash

46. •Rash: centripetal in distribution; more in the trunk, sparing
the limbs; superficial; appear in crops
•Macule  Papule  Vesicle  Pustule  scab stages
develop very rapidly
•The blisters open and form a scab within a few days.
•The rash can continue to break out for 4-5 days as older
lesions crust and heal.

47. •Itching can accompany the rash along with fever, swollen
lymph nodes, sore throat and general body aches.
•Attack confers lasting immunity
•One of the mildest & most common of childhood infections
•Adult chicken pox is more serious

48. Varicella (Chickenpox)
Chickenpox vesicle behind the ear.
Notice the translucent quality of the
vesicle on the skin, the classic "dew
drop on a rose petal" appearance.
Chickenpox on the palate. Notice
the glistening, water-drop
characteristic of the chickenpox
vesicle on the palate.

49. Varicella (Chickenpox) View Table
Chickenpox on the hand. Notice
the simultaneous occurrence of
lesions in different stages of
development.
Chickenpox in an infant. Notice
the rose-colored macules,
papules, vesicles, pustules,
necrotic pustules, and crusted
lesions occurring simultaneously.

50. Differential Dx - Chickenpox
Variola (Smallpox)
 Begins centrally, then
spreads outward to face and
extremities
 All lesions are always in a
single stage of development
 Associated with severe
constitutional symptoms
Chickenpox
 Begins on the face and scalp,
spreads to the trunk
 Lesions in various stages of
development can
simultaneously be present on
the patient's skin

51. C
omplications of chicken
C
omplications of chicken
p
ox
p
ox
•Varicella pneumonia
•Myocarditis
•Nephritis
•Acute cerebellar ataxia
•Meningitis
•Encephalitis
•Reye’s syndrome
•Complications of pregnancy
•Fetal varicella syndrome
•Congenital/neonatal
varicella syndrome

52. H
erpes zoster
H
erpes zoster
•Synonyms: Shingles, Zona
•Disease of old age; rarely in the newborn
•Usually is a latent infection; associated with reactivation of the
dormant viruses in the sensory ganglia
•Reactivation is associated with inflammation of the nerve which lead
to neuritic pain that often precedes the skin lesions. Pain is often
very sever and persists for weeks or months.
•Typical unilateral rash & confined to a single dermatome
•Most common dermatomes affected- D3 to L2 & trigeminal nerve

53. •Vesicles same like a varicella
•Thoracic nerve (commonly) ophthalmic branch of
trigeminal nerve (ophthalmic Zoster)
•Complications: LMN paralysis, meningoencephalitis,
herpes zoster ophthalmicus, Ramsay-Hunt
syndrome, generalized zoster
•Diagnosis & Rx are similar to that of varicella

54. Recurrent varicella zoster on the Recurrent varicella zoster on the
right side of the face; Shingles right side of the face; Shingles
affecting the left side of the trunk
 
affecting the left side of the trunk
 

55. Ramsay-Hunt syndrome Ramsay-Hunt syndrome
causing a right-sided facial palscausing a right-sided facial palsyy
Affecting facial nerve
Erruption on tympanic
membrane & external
auditory canal with often
facial palsy.

56. Zo
ster: Dermatomal
Zo
ster: Dermatomal
D
istribution
D
istribution
Image courtesy of Charles E. Crutchfield III, MD.

57. Zoster
Ophthalmicus
Zoster
Ophthalmicus
Image courtesy of
Charles E. Crutchfield III, MD.
KO Studios, Pacifica, CA.
©2002. Reprinted with permission.
Image courtesy of
Dr. Dubin’s collection (www.skinatlas.com)

58. Herpes Zoster (Shingles)
Herpes (varicella) zoster
on the arm. Notice the
characteristic grouping of
vesicles
Varicella zoster on the face.
Notice the dermatomal
distribution of the papules,
vesicles, and pustules.

59. L
ab diagnosis
L
ab diagnosis
•Mainly clinical
•Multinucleated giant cells & type A intranuclear inclusions in
Tzanck smears and stained with toluidine blue or Giemsa stain.
•EM of the vesicle fluid to demonstrate the virus
•Virus isolation from buccal or cutaneous lesions in the early
stages in human amnion, human fibroblast, HeLa or Vero cell
lines – cytopathic effect is focal with refractile ballooned cells.
•IF for skin lesions; CIE for vesicle fluid
•ELISA & PCR ( VZV in CSF and other body fluids)

60. T
reatment
T
reatment
•Specific therapy reqd. only in complicated cases, elderly
& in ID patients
•Acyclovir & Vidarabine are the antiviral agents found to
be effective

61. •Varicella Zoster Immune Globulin (VZIG)
•Only offers temporary protection
•Recommended for:
Newborns whose mothers have chickenpox 5 days prior to 2 days after
delivery
Children with leukemia or lymphoma who have not been vaccinated
Persons with cellular immunodeficiencies or other immune problems
Persons receiving drugs, including steroids, that suppress the immune
system
Pregnant women
P
rophylaxis
P
rophylaxis

62. P
rophylaxis
P
rophylaxis
Live varicella vaccine
•Developed by attenuation of Oka strain of varicella
(Takahashi, 1974)
•Administered subcutaneously
•Single dose for children 1-12 yr
•Double dose for adult
•Safe and effective
•Not safe in pregnancy.

64. Summary

Summary

•All the major herpesviruses are found worldwide.
•HSV-1 and 2 cause mucocutaneous vesicular and ulcerative
lesions
•Infection is transmitted following contact between the infected
and non infected hosts : oral or genital ( or both)
•Pathogenesis - Replication occurs in local epitherial cells until
eruption occurs on the surface as vesicles.
•Both humoral and cell medicated immune response are
important.

65. Summary

Summary

•Varicella zoster virus ( VZV) is the cause
1. Chicken pox( Varicella)
•A vesicular rash mainly seen in children that starts at
the head and trunk and moves to the extremities
•Vesicles may become pustular, crusted and scabbed prior
to healing.
2. VZV infection usually manifests as zoster or shingles
•Characterized by painful vesicular lesions along the
distribution of a single nerve.

66. Summary

Summary

•Infection is transmitted by aerosols from infected individual.
•Pathogenesis - Initial infection of epitheial cells of the
nasopharynx in a susceptible individual is followed by viral
replication, viremia, skin rashes and latency in the dorsal
root ganglia.
•Later life VZV may emerge to cause zoster.
•Humeral and cell meditated immunity are important in
determining the outcome of infection.

67. E
pstein- Barr Virus (HHV-4)
E
pstein- Barr Virus (HHV-4)
•The virus named after the discoverers Epstein and Barr who
isolated it from Burkitt’s lymphoma.
•Epstein Barr virus has affinity for lymphoid tissue.
•B lymphocytes of human beings have receptors(CD21
molecules) for EBV therefore the virus specially affects these
cells.
•EBV infected B lymphocytes are transformed in such a way that
they multiply continuously
•These transformed cells contain many EBV genomes.

68. •EBV is ubiquitous in all human populations.
•80 – 90 % children acquire infection by age of 3 yrs.
•Most infections are inapparent. Once infected, the virus is
present in the individual for life.
•Source of infection is usually the saliva of infected persons
who shed the virus in oropharyngeal secretions.
C
linical manifestations
C
linical manifestations

69. •Virus is not highly contagious and droplets and
aerosols are not efficient in transmitting infection.
•Intimate oral contact, as in Kissing, appears to be
main mode of transmission.
•Onocogenic properties.
C
linical manifestations
C
linical manifestations

70. •Following clinical manifestations may result from EBV
infection
1.Infectious mononucleosis or Glandular fever
2.Infections in immunocompromised hosts.
3.EBV associated malignancies.

71. Infectious mononucleosis/ Glandular feverInfectious mononucleosis/ Glandular fever
•It is a self limiting disease of children and young adults
occasionally develop the disease as a consequence of primary
EBV infection, and rarely also the elderly.
•Incubation period is 4 to 7 weeks
•Infection is believed to occurs through respiratory route by close
contact with patients.
•Disease is mainly transmitted by kissing (kissing disease)
•Disease usually lasts for 2-3 weeks.

72. It is characterized by
•Fever, Sore throat,
•Generalized lymphadenopathy is almost invariable, most
marked in the cervical region, with symmetrical, discrete,
slightly tender glands;
•Splenomegaly is seen in 60% of cases,
•An enlarged liver in 10% and actual jaundice in about 8%.

73. •The presence of abnormal lymohocytes in the
peripheral blood
•It activates B lymphocytes and leads to secretion of
immunogobulin.
•IgM producing B lymphocytes predominate that
produce high levels of IgM.

74. Infections in immunocompromised Hosts
•Cause progressive lymphoproliferative disease in
immnunodeficient children, transplant recipients and AIDS
patients.
EBV – associated Malignancies.
1. Burkitt’s lymphoma
•It is a malignant neoplasm of B-lymphocytes (tumour of jaw)
•Occurs in regions of Africa and New Guniea.
•Disease occurs in endemic or sporadic type
•Cells of Burkitt’s lumphoma carry multiple copies of EBV
genome.

75. 2. Nasopharyngeal carcinoma
•It is found in the males of Chinese origin in South- East
Asia and East Africa.
•EB viral DNA is regularly present in the malignant
epithelial cells of the tumour.
3. B-cell lymphoma.
•Recipients of transplants and HIV infected patients may
develop EBV associated B – cell lymphoma.

76. Virus enters the pharyngeal epithelial cell through CD21 receptors
It multiplies locally and enter bloodstream
Infect B lymphocytes
Virus remains latent inside the lymphocytes which become transformed
These transformed cells are capable of indefinite growth in vitro.
Pathogensis Pathogensis

77. Finally they are polyconally activated and produce
many types of immunoglobulins
Some of the infected B lymphocytes show lytic
infection with cell death and release of progeny
virions.

78. •EB virus antigens are expressed on the surface of
infected B lymphocytes
•T lymphocytes undergo blast transformation in response
to such neoantigens.
( These lymphocytes are seen as atypical lymphocytes in
blood smears on infectious mononucleoasis patients)

79. •Reactivation of latent virus leads to clonal proliferation of
infected B lymphocytes.
–In immunocompetent individuals this is kept check by T
lymphocytes
–In immunodeficient persons lymphoma may occurs
because of unchecked replication of B lymphocyte clone.
•Lymphoma contains EB virus DNA and it regularly found
in tumour cells.

80. L
ab diagnosis of EBV
L
ab diagnosis of EBV
1. White Blood Cell Count
•Leucopenia, followed by leucocytosis with abnormal
mononuclear cells in blood
•These atypical cells are lymphoblasts derived from T
cells reactive to the virus infection.
•These constitute 30-90% of total leucocytes.

81. 2. Paul-Bunnell test: Heterophile agglutination test
•During IM heterophile antibodies(IgM) appear in the
serum of the patient.
•Antibodies appear in 85-90% of patients sera during the
acute phase of illness.
•Their titre decreases rapidly after 4
th
week and are non
detectable after 3 months.

82. Procedure
•Inactivated serum (56
0
C for 30 min) in doubling
dilutions is mixed with equal volumes of 1% sheep
erythrocytes suspension.
•Tubes are incubated at 37
0
C for 4 hours
•Examined for agglutination.
•A titer of 100 or above is suggestive of IM.

83. Confirmation ( differential agglutination test)
•Similar type of antibodies may occur after injection of
sera and even sometime in normal individuals
•To confirm these antibodies , absorption of agglutinins
with pig kidney and ox red cells is necessary.
ABSORPTION WITH
Guinea pig kidney Ox red cells
Normal serum Absorbed Not Absorbed
Antibody after serum
injection
Absorbed Absorbed
Infectious MononucleosisNot Absorbed Absorbed

84. 3. EBV-specific antibodies
1.Viral capsid antigen (VCA)
•IgM type appears soon after infection and disappears in 1-2
weeks (indicates primary infection)
•IgG type persists throughout life ( indicates past infection
Demonstrated by
•Indirect immunoflurescence or ELISA.
2. EB nuclear antigen (EBNA)

85. 4. Antigen detection
•Can be detected by immunofluorescence using monoclonal
antibodies.
5. Virus isolation
•Saliva or throat washing and peripheral blood cells can be
inoculated into lymphocytes
•If specimen contains EBV it produce a lymphoblastoid cell line.
6. PCR
•EBV DNA can be detected by PCR

86. •Infection with CMV is common in all populations and
infrequently associated with symptomatic illness in
normal hosts.
•In contrast, it is a major cause of multi-organ disease in
immunocompromised patients, the severity of disease
being related to the degree of immunosuppression.
•Largest viruses in the Herpes family (150-200 nm)
•Characterized by enlargement of the infected cells &
intranuclear inclusions
C
ytomegalovirus (HHV-5)
C
ytomegalovirus (HHV-5)

87. •Human cytomegalovirus can be grown in human fibroblast
cultures
•Culture have be incubated for prolonged periods as the
cytopathic effects are slow in appearance.
•CMV infection is always inapparent , leading to prolonged
latency, with occasional reactivation.
•Individual infected with CMV carries life long.
•Virus shed in urine, saliva, semen, cervical secretions, tears
and breast milk.
•10% healthy women may carry virus in cervix.

88. Cytomegalovirus can be transmitted
1. Transplacentally from a mother with latent infection to
the foetus.
–Congenital infection may remain inapparent at birth
or may leads to cytomegalic inclusion disease
–The disease characterized by hepatosplenomegaly,
jaundice, thrombocytopenic purpura, mecrocephaly
and chorioretinitis.
Pathogenesis Pathogenesis

89. 2. May also acquired by sexual intercourse, blood transfusion
and organ transplantation.
•Clinical disease in adult resembles IM
•It may also cause hepatits or pneumonitis
•It may cause disseminated infection in
immunocomprimised individuals and can lead to fatal
infections
•CMV is an important pathogen in AIDS

90. 1. Specimen
•CMV isolated from urine, saliva, breast milk, semen, cervical
secretions and blood leucocytes.
2. Demonstration of Cytomegalic cells.
•Enlarge cells with large intranuclear “owl’s eye” appearance
inclusions (cytomegalic cells) can be demonstrated in the
centrifuged deposits from urine and saliva
L
ab diagnosis
L
ab diagnosis

91. 3. Isolation of Virus
•Grown in human fibroblast cultures.
•Virus replicates very slowly therefore cytopathic effects
(swollen refractile cells with cytoplasmic granules) may take
2-3 weeks to appear.
•These culture may stained by immunofluorescence technique
using monoclonal antibody.

92. 4. Antigen detection
•CMV antigen can be detected from blood leucocytes
using monoclonal antibodies
5. PCR
•Most widely used molecular method for detection of
CMV DNA
6. Serology
•CMV- specific IgM can be detected in the serum by
ELISA.

93. •HHV6 infects dividing CD4 T lymphocytes and Macrophages.
•Saliva is main route of transmission
•Most HHV-6 infection appears asymptomatic
•In children HHV-6 Causes sixth disease also exanthem
subitum or roseola infantum characterized by high grade fever
and skin rashes.
•In old age group associated with mononucleosis with cervical
lymphadenopathy.
HUMAN HERPES VIRUS 6HUMAN HERPES VIRUS 6

94. Laboratory Diagnosis
•Isolated from peripheral blood mononuclear cells is early
febrile stage of the illness by cocultivation with
lymphocytes.
•Virus antigen can be detected by immunofluorescence using
monoclonal antibodies
•Both antigen and antibodies can be detected in patient
serum by ELISA.

95. •Like HHV-6 it may also cause roseola infantum.
•Both HHV-6 and HHV-7 infect T lymphocytes using
same CD4 receptors.
•Associated with fever, seizures, respiratory or
gastrointestinal signs and pityriasis rosea.
HUMAN HERPES VIRUS 7HUMAN HERPES VIRUS 7

96. •HHV-8 was first discovered in 1994 in pts with Kaposi’s
sarcoma hence also called Kaposi’s sarcoma associated
herpesvirus.
Pathogenesis
•HHV-8 infects B cells and genome possesses several
oncogenes that regulate certain host cell functions such as
proliferation and apoptosis.
•Which is commonest tumor in HIV infected individuals
HUMAN HERPES VIRUS 8HUMAN HERPES VIRUS 8

97. In immunocompromized individuals
•It is associated with
– Kaposi’s sarcoma
–Primary effusion lymphoma
–Castleman’s disease ( lymphoproliferative disorder of B
cells)
In immunocompetent host
–It produces fever and rash.

98. Diagnosis
•HHV-8 can be detected by PCR is the most confirmatory assay.
•Isolation is difficult.
•Antibody detection assays are available in various such as
indirect-IF, Western blot, and ELISA.
Treatment
•Respond well to forcarnet, ganciclavir and cidofovir
•Effective antiretroviral therapy for HIV-infected individuals
can reduce the risk of Kaposi’s sarcoma in HHV-8 infected
people.